02995nas a2200349 4500008004100000022001400041245007200055210006900127260001300196300001100209490000800220520199600228653003902224653000902263653002002272653001902292653002602311653004002337653001102377653001102388653002602399653001802425653001702443653001702460100002002477700002202497700002402519700002202543700002002565700002502585856003502610 2004 eng d a1097-674400aRacial differences in endothelial function in postmenopausal women.0 aRacial differences in endothelial function in postmenopausal wom c2004 Oct a606-110 v1483 a
OBJECTIVE: Racial differences in cardiovascular mortality among women remain largely unexplained. Preliminary data suggest that African American and Caucasian differences in endothelial function may parallel differential cardiovascular disease (CVD) risk in women. To further study differences in endothelial function between African American and Caucasian women, we analyzed measures of brachial artery flow-mediated dilation (FMD) in women enrolled in the Cardiovascular Health Study (CHS).
METHODS AND RESULTS: Brachial artery FMD was measured in the fasting state using established ultrasound techniques in 1330 Caucasian and 297 African American female participants in CHS (mean age 78.4 +/- 4.4 years). General linear models were used to compare FMD between African American and Caucasian women after adjusting for baseline brachial diameter, hypertension, diabetes, smoking, cholesterol, systolic blood pressure, body mass index, waist/hip ratio, age, education, income level; use of angiotensin-converting enzyme inhibitors, beta-blockers, nitroglycerin, estrogens and lipid-lowering drugs; and presence of clinical or subclinical disease. Adjusted absolute change and percent change in brachial artery diameter was significantly reduced in African American women compared with Caucasian women (P <.0001 and P =.0002, respectively). Similar results were found when the women were stratified by history of CVD (- CVD, P =.02; + CVD, P =.001) and CVD or subclinical vascular disease (- disease, P =.01, + disease, P =.03).
CONCLUSIONS: In this cohort, brachial artery FMD was lower in African American women compared to Caucasian women, and this difference persisted after adjustment by multivariable analysis. The increased CVD risk in African American women may be related to impaired endothelial function. It remains to be determined whether African American women may uniquely benefit by interventions designed to improve endothelial health.
10aAfrican Continental Ancestry Group10aAged10aBrachial Artery10aCohort Studies10aEndothelium, Vascular10aEuropean Continental Ancestry Group10aFemale10aHumans10aMultivariate Analysis10aPostmenopause10aRisk Factors10aVasodilation1 aLoehr, Laura, R1 aEspeland, Mark, A1 aSutton-Tyrrell, Kim1 aBurke, Gregory, L1 aCrouse, John, R1 aHerrington, David, M uhttps://chs-nhlbi.org/node/80604239nas a2200781 4500008004100000022001400041245024400055210006900299260001300368300001100381490000600392520185900398653002202257653000902279653002202288653001902310653001902329653004002348653001102388653003402399653001802433653001102451653001402462653000902476653001602485653003602501653000902537653003302546100002302579700002102602700002402623700002302647700002202670700002002692700002502712700001902737700001902756700002302775700001902798700002602817700001902843700002102862700002102883700002402904700002302928700001802951700002102969700001802990700002303008700002403031700002303055700002003078700002103098700001903119700002303138700001803161700003003179700002803209700002203237700002403259700001703283700002303300700002003323700003003343700002103373700002703394856003603421 2010 eng d a1942-326800aAssociation of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.0 aAssociation of genomewide variation with the risk of incident he c2010 Jun a256-660 v33 aBACKGROUND: Although genetic factors contribute to the onset of heart failure (HF), no large-scale genome-wide investigation of HF risk has been published to date. We have investigated the association of 2,478,304 single-nucleotide polymorphisms with incident HF by meta-analyzing data from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study.
METHODS AND RESULTS: Eligible participants for these analyses were of European or African ancestry and free of clinical HF at baseline. Each study independently conducted genome-wide scans and imputed data to the approximately 2.5 million single-nucleotide polymorphisms in HapMap. Within each study, Cox proportional hazards regression models provided age- and sex-adjusted estimates of the association between each variant and time to incident HF. Fixed-effect meta-analyses combined results for each single-nucleotide polymorphism from the 4 cohorts to produce an overall association estimate and P value. A genome-wide significance P value threshold was set a priori at 5.0x10(-7). During a mean follow-up of 11.5 years, 2526 incident HF events (12%) occurred in 20 926 European-ancestry participants. The meta-analysis identified a genome-wide significant locus at chromosomal position 15q22 (1.4x10(-8)), which was 58.8 kb from USP3. Among 2895 African-ancestry participants, 466 incident HF events (16%) occurred during a mean follow-up of 13.7 years. One genome-wide significant locus was identified at 12q14 (6.7x10(-8)), which was 6.3 kb from LRIG3.
CONCLUSIONS: We identified 2 loci that were associated with incident HF and exceeded genome-wide significance. The findings merit replication in other community-based settings of incident HF.
10aAfrican Americans10aAged10aAged, 80 and over10aCohort Studies10aEndopeptidases10aEuropean Continental Ancestry Group10aFemale10aGenome-Wide Association Study10aHeart Failure10aHumans10aIncidence10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aRisk10aUbiquitin-Specific Proteases1 aSmith, Nicholas, L1 aFelix, Janine, F1 aMorrison, Alanna, C1 aDemissie, Serkalem1 aGlazer, Nicole, L1 aLoehr, Laura, R1 aCupples, Adrienne, L1 aDehghan, Abbas1 aLumley, Thomas1 aRosamond, Wayne, D1 aLieb, Wolfgang1 aRivadeneira, Fernando1 aBis, Joshua, C1 aFolsom, Aaron, R1 aBenjamin, Emelia1 aAulchenko, Yurii, S1 aHaritunians, Talin1 aCouper, David1 aMurabito, Joanne1 aWang, Ying, A1 aStricker, Bruno, H1 aGottdiener, John, S1 aChang, Patricia, P1 aWang, Thomas, J1 aRice, Kenneth, M1 aHofman, Albert1 aHeckbert, Susan, R1 aFox, Ervin, R1 aO'Donnell, Christopher, J1 aUitterlinden, André, G1 aRotter, Jerome, I1 aWillerson, James, T1 aLevy, Daniel1 aDuijn, Cornelia, M1 aPsaty, Bruce, M1 aWitteman, Jacqueline, C M1 aBoerwinkle, Eric1 aVasan, Ramachandran, S uhttps://chs-nhlbi.org/node/119704080nas a2200757 4500008004100000022001400041245019100055210006900246260001300315300001100328490000600339520181900345653002202164653000902186653002202195653001502217653001902232653004002251653001102291653003402302653001302336653001802349653001102367653001202378653000902390653003802399653002202437653001602459653003602475653001702511100002402528700002102552700002502573700002202598700002002620700001902640700002302659700001902682700002302701700002402724700001802748700002302766700002102789700002602810700002402836700001902860700001802879700002302897700003002920700002102950700002302971700001902994700001703013700002203030700001803052700002803070700002003098700002003118700002403138700002303162700002103185700003003206700002703236700002303263856003603286 2010 eng d a1942-326800aGenomic variation associated with mortality among adults of European and African ancestry with heart failure: the cohorts for heart and aging research in genomic epidemiology consortium.0 aGenomic variation associated with mortality among adults of Euro c2010 Jun a248-550 v33 aBACKGROUND: Prognosis and survival are significant concerns for individuals with heart failure (HF). To better understand the pathophysiology of HF prognosis, the association between 2,366,858 single-nucleotide polymorphisms (SNPs) and all-cause mortality was evaluated among individuals with incident HF from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study.
METHODS AND RESULTS: Participants were 2526 individuals of European ancestry and 466 individuals of African ancestry who experienced an incident HF event during follow-up in the respective cohorts. Within each study, the association between genetic variants and time to mortality among individuals with HF was assessed by Cox proportional hazards models that included adjustment for sex and age at the time of the HF event. Prospective fixed-effect meta-analyses were conducted for the 4 study populations of European ancestry (N=1645 deaths) and for the 2 populations of African ancestry (N=281 deaths). Genome-wide significance was set at P=5.0x10(-7). Meta-analytic findings among individuals of European ancestry revealed 1 genome-wide significant locus on chromosome 3p22 in an intron of CKLF-like MARVEL transmembrane domain containing 7 (CMTM7, P=3.2x10(-7)). Eight additional loci in individuals of European ancestry and 4 loci in individuals of African ancestry were identified by high-signal SNPs (P<1.0x10(-5)) but did not meet genome-wide significance.
CONCLUSIONS: This study identified a novel locus associated with all-cause mortality among individuals of European ancestry with HF. This finding warrants additional investigation, including replication, in other studies of HF.
10aAfrican Americans10aAged10aAged, 80 and over10aChemokines10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aGenome-Wide Association Study10aGenotype10aHeart Failure10aHumans10aIntrons10aMale10aMARVEL Domain-Containing Proteins10aMembrane Proteins10aMiddle Aged10aPolymorphism, Single Nucleotide10aRisk Factors1 aMorrison, Alanna, C1 aFelix, Janine, F1 aCupples, Adrienne, L1 aGlazer, Nicole, L1 aLoehr, Laura, R1 aDehghan, Abbas1 aDemissie, Serkalem1 aBis, Joshua, C1 aRosamond, Wayne, D1 aAulchenko, Yurii, S1 aWang, Ying, A1 aHaritunians, Talin1 aFolsom, Aaron, R1 aRivadeneira, Fernando1 aBenjamin, Emelia, J1 aLumley, Thomas1 aCouper, David1 aStricker, Bruno, H1 aO'Donnell, Christopher, J1 aRice, Kenneth, M1 aChang, Patricia, P1 aHofman, Albert1 aLevy, Daniel1 aRotter, Jerome, I1 aFox, Ervin, R1 aUitterlinden, André, G1 aWang, Thomas, J1 aPsaty, Bruce, M1 aWillerson, James, T1 aDuijn, Cornelia, M1 aBoerwinkle, Eric1 aWitteman, Jacqueline, C M1 aVasan, Ramachandran, S1 aSmith, Nicholas, L uhttps://chs-nhlbi.org/node/118702822nas a2200637 4500008004100000022001400041245011200055210006900167260001300236300001000249490000700259520095900266653002301225653001101248653002901259653003801288653001801326653003401344653001101378653000901389653001801398653000901416653002701425653003601452653001501488653001901503100002101522700002201543700001901565700002001584700002001604700002601624700002301650700003001673700001901703700001701722700002501739700002101764700002201785700002001807700002301827700002201850700002801872700001901900700002301919700002601942700002401968700002101992700001902013700002302032700001902055700002502074700002402099700002502123856003602148 2010 eng d a1546-171800aMeta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.0 aMetaanalyses of genomewide association studies identify multiple c2010 Jan a45-520 v423 aSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV(1)) and its ratio to forced vital capacity (FEV(1)/FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE Consortium studies: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study and Rotterdam Study. We identified eight loci associated with FEV(1)/FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1 and HTR4) and one locus associated with FEV(1) (INTS12-GSTCD-NPNT) at or near genome-wide significance (P < 5 x 10(-8)) in the CHARGE Consortium dataset. Our findings may offer insights into pulmonary function and pathogenesis of chronic lung disease.
10aDatabases, Genetic10aFemale10aForced Expiratory Volume10aGenetic Predisposition to Disease10aGenome, Human10aGenome-Wide Association Study10aHumans10aLung10aLung Diseases10aMale10aMeta-Analysis as Topic10aPolymorphism, Single Nucleotide10aSpirometry10aVital Capacity1 aHancock, Dana, B1 aEijgelsheim, Mark1 aWilk, Jemma, B1 aGharib, Sina, A1 aLoehr, Laura, R1 aMarciante, Kristin, D1 aFranceschini, Nora1 avan Durme, Yannick, M T A1 aChen, Ting-Hsu1 aBarr, Graham1 aSchabath, Matthew, B1 aCouper, David, J1 aBrusselle, Guy, G1 aPsaty, Bruce, M1 aDuijn, Cornelia, M1 aRotter, Jerome, I1 aUitterlinden, André, G1 aHofman, Albert1 aPunjabi, Naresh, M1 aRivadeneira, Fernando1 aMorrison, Alanna, C1 aEnright, Paul, L1 aNorth, Kari, E1 aHeckbert, Susan, R1 aLumley, Thomas1 aStricker, Bruno, H C1 aO'Connor, George, T1 aLondon, Stephanie, J uhttps://chs-nhlbi.org/node/115007169nas a2202257 4500008004100000022001400041245010400055210006900159260001600228300001200244490000700256520086500263653001001128653004001138653003401178653001101212653004301223653003101266100002601297700001801323700002001341700002001361700001901381700001601400700001801416700001901434700002601453700002501479700001801504700002601522700002001548700001701568700002001585700002101605700002001626700001801646700002401664700001901688700001901707700002001726700002501746700002101771700002401792700002301816700002001839700002201859700002901881700001901910700002801929700002101957700002201978700002602000700002302026700002402049700001802073700001902091700001902110700002102129700002302150700002102173700001802194700001602212700002802228700002202256700001702278700002002295700001702315700002002332700001902352700002602371700001602397700001702413700001702430700002002447700001802467700001902485700001902504700002102523700002202544700001802566700001902584700002002603700001802623700001802641700002202659700001902681700001902700700002002719700001702739700002302756700001902779700002102798700002002819700001802839700002402857700001902881700002102900700001602921700002302937700001902960700002202979700001903001700001803020700002403038700001803062700002303080700002103103700002203124700002103146700002303167700002203190700002103212700001903233700002603252700002003278700002203298700001603320700001803336700002403354700001703378700001903395700002803414700002003442700002203462700002203484700002003506700001903526700001703545700002103562700002603583700002203609700001903631700002403650700001903674700001903693700002003712700002703732700001803759700002603777700001803803700002003821700002803841700002003869700002003889700002203909700001603931700002403947700001903971700001803990700002004008700001704028700002204045700001904067700002504086700002604111700002204137700001904159700001904178700001904197700002004216700001604236700002204252700002204274700002004296700001504316700002204331700001904353700002204372700002304394700002604417700001904443700002104462700002204483700002004505700002204525700002004547700002304567700001804590700002704608700002604635700001804661700002404679700002304703700002504726700001704751700002404768700002104792710004104813710002104854856003604875 2011 eng d a1546-171800aGenome-wide association and large-scale follow up identifies 16 new loci influencing lung function.0 aGenomewide association and largescale follow up identifies 16 ne c2011 Sep 25 a1082-900 v433 aPulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
10aChild10aEuropean Continental Ancestry Group10aGenome-Wide Association Study10aHumans10aPulmonary Disease, Chronic Obstructive10aRespiratory Function Tests1 aArtigas, Maria, Soler1 aLoth, Daan, W1 aWain, Louise, V1 aGharib, Sina, A1 aObeidat, Ma'en1 aTang, Wenbo1 aZhai, Guangju1 aZhao, Jing Hua1 aSmith, Albert, Vernon1 aHuffman, Jennifer, E1 aAlbrecht, Eva1 aJackson, Catherine, M1 aEvans, David, M1 aCadby, Gemma1 aFornage, Myriam1 aManichaikul, Ani1 aLopez, Lorna, M1 aJohnson, Toby1 aAldrich, Melinda, C1 aAspelund, Thor1 aBarroso, Inês1 aCampbell, Harry1 aCassano, Patricia, A1 aCouper, David, J1 aEiriksdottir, Gudny1 aFranceschini, Nora1 aGarcia, Melissa1 aGieger, Christian1 aGislason, Gauti, Kjartan1 aGrkovic, Ivica1 aHammond, Christopher, J1 aHancock, Dana, B1 aHarris, Tamara, B1 aRamasamy, Adaikalavan1 aHeckbert, Susan, R1 aHeliövaara, Markku1 aHomuth, Georg1 aHysi, Pirro, G1 aJames, Alan, L1 aJankovic, Stipan1 aJoubert, Bonnie, R1 aKarrasch, Stefan1 aKlopp, Norman1 aKoch, Beate1 aKritchevsky, Stephen, B1 aLauner, Lenore, J1 aLiu, Yongmei1 aLoehr, Laura, R1 aLohman, Kurt1 aLoos, Ruth, J F1 aLumley, Thomas1 aBalushi, Khalid, A Al1 aAng, Wei, Q1 aBarr, Graham1 aBeilby, John1 aBlakey, John, D1 aBoban, Mladen1 aBoraska, Vesna1 aBrisman, Jonas1 aBritton, John, R1 aBrusselle, Guy, G1 aCooper, Cyrus1 aCurjuric, Ivan1 aDahgam, Santosh1 aDeary, Ian, J1 aEbrahim, Shah1 aEijgelsheim, Mark1 aFrancks, Clyde1 aGaysina, Darya1 aGranell, Raquel1 aGu, Xiangjun1 aHankinson, John, L1 aHardy, Rebecca1 aHarris, Sarah, E1 aHenderson, John1 aHenry, Amanda1 aHingorani, Aroon, D1 aHofman, Albert1 aHolt, Patrick, G1 aHui, Jennie1 aHunter, Michael, L1 aImboden, Medea1 aJameson, Karen, A1 aKerr, Shona, M1 aKolcic, Ivana1 aKronenberg, Florian1 aLiu, Jason, Z1 aMarchini, Jonathan1 aMcKeever, Tricia1 aMorris, Andrew, D1 aOlin, Anna-Carin1 aPorteous, David, J1 aPostma, Dirkje, S1 aRich, Stephen, S1 aRing, Susan, M1 aRivadeneira, Fernando1 aRochat, Thierry1 aSayer, Avan Aihie1 aSayers, Ian1 aSly, Peter, D1 aSmith, George Davey1 aSood, Akshay1 aStarr, John, M1 aUitterlinden, André, G1 aVonk, Judith, M1 aWannamethee, Goya1 aWhincup, Peter, H1 aWijmenga, Cisca1 aWilliams, Dale1 aWong, Andrew1 aMangino, Massimo1 aMarciante, Kristin, D1 aMcArdle, Wendy, L1 aMeibohm, Bernd1 aMorrison, Alanna, C1 aNorth, Kari, E1 aOmenaas, Ernst1 aPalmer, Lyle, J1 aPietiläinen, Kirsi, H1 aPin, Isabelle1 aEk, Ozren, Pola Sbrev1 aPouta, Anneli1 aPsaty, Bruce, M1 aHartikainen, Anna-Liisa1 aRantanen, Taina1 aRipatti, Samuli1 aRotter, Jerome, I1 aRudan, Igor1 aRudnicka, Alicja, R1 aSchulz, Holger1 aShin, So-Youn1 aSpector, Tim, D1 aSurakka, Ida1 aVitart, Veronique1 aVölzke, Henry1 aWareham, Nicholas, J1 aWarrington, Nicole, M1 aWichmann, H-Erich1 aWild, Sarah, H1 aWilk, Jemma, B1 aWjst, Matthias1 aWright, Alan, F1 aZgaga, Lina1 aZemunik, Tatijana1 aPennell, Craig, E1 aNyberg, Fredrik1 aKuh, Diana1 aHolloway, John, W1 aBoezen, Marike1 aLawlor, Debbie, A1 aMorris, Richard, W1 aProbst-Hensch, Nicole1 aKaprio, Jaakko1 aWilson, James, F1 aHayward, Caroline1 aKähönen, Mika1 aHeinrich, Joachim1 aMusk, Arthur, W1 aJarvis, Deborah, L1 aGläser, Sven1 aJarvelin, Marjo-Riitta1 aStricker, Bruno, H Ch1 aElliott, Paul1 aO'Connor, George, T1 aStrachan, David, P1 aLondon, Stephanie, J1 aHall, Ian, P1 aGudnason, Vilmundur1 aTobin, Martin, D1 aInternational Lung Cancer Consortium1 aGIANT Consortium uhttps://chs-nhlbi.org/node/609605378nas a2201249 4500008004100000022001400041245010600055210006900161260001600230300001100246490000800257520186000265653000902125653001102134653002902145653003402174653001102208653000902219653001602228653002602244653003602270653004302306653002502349653003202374653001202406653001902418100001902437700002202456700002002478700001902498700002102517700002002538700002602558700002302584700002202607700001602629700001802645700001902663700001602682700002002698700002602718700002102744700002102765700001502786700002002801700002002821700002302841700002202864700002402886700001902910700001802929700002002947700001702967700001902984700002303003700001903026700002103045700002203066700001903088700001903107700001903126700001803145700001903163700002203182700002203204700001703226700002003243700002003263700001903283700002603302700002203328700001903350700002403369700002003393700002203413700001903435700002203454700002003476700002103496700002603517700002003543700002203563700002603585700001903611700002803630700002503658700002003683700001803703700002503721700002403746700001803770700002003788700002503808700002403833700001703857700002003874700002303894700002503917700001903942700002603961700002003987700001704007700002404024700002104048700002304069856003604092 2012 eng d a1535-497000aGenome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction.0 aGenomewide association studies identify CHRNA53 and HTR4 in the c2012 Oct 01 a622-320 v1863 aRATIONALE: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known.
OBJECTIVES: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases.
METHODS: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV(1) and its ratio to FVC (FEV(1)/FVC) both less than their respective lower limits of normal as determined by published reference equations.
MEASUREMENTS AND MAIN RESULTS: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV(1)/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis.
CONCLUSIONS: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction.
10aAged10aFemale10aForced Expiratory Volume10aGenome-Wide Association Study10aHumans10aMale10aMiddle Aged10aNerve Tissue Proteins10aPolymorphism, Single Nucleotide10aPulmonary Disease, Chronic Obstructive10aReceptors, Nicotinic10aReceptors, Serotonin, 5-HT410aSmoking10aVital Capacity1 aWilk, Jemma, B1 aShrine, Nick, R G1 aLoehr, Laura, R1 aZhao, Jing Hua1 aManichaikul, Ani1 aLopez, Lorna, M1 aSmith, Albert, Vernon1 aHeckbert, Susan, R1 aSmolonska, Joanna1 aTang, Wenbo1 aLoth, Daan, W1 aCurjuric, Ivan1 aHui, Jennie1 aCho, Michael, H1 aLatourelle, Jeanne, C1 aHenry, Amanda, P1 aAldrich, Melinda1 aBakke, Per1 aBeaty, Terri, H1 aBentley, Amy, R1 aBorecki, Ingrid, B1 aBrusselle, Guy, G1 aBurkart, Kristin, M1 aChen, Ting-Hsu1 aCouper, David1 aCrapo, James, D1 aDavies, Gail1 aDupuis, Josée1 aFranceschini, Nora1 aGulsvik, Amund1 aHancock, Dana, B1 aHarris, Tamara, B1 aHofman, Albert1 aImboden, Medea1 aJames, Alan, L1 aKhaw, Kay-Tee1 aLahousse, Lies1 aLauner, Lenore, J1 aLitonjua, Augusto1 aLiu, Yongmei1 aLohman, Kurt, K1 aLomas, David, A1 aLumley, Thomas1 aMarciante, Kristin, D1 aMcArdle, Wendy, L1 aMeibohm, Bernd1 aMorrison, Alanna, C1 aMusk, Arthur, W1 aMyers, Richard, H1 aNorth, Kari, E1 aPostma, Dirkje, S1 aPsaty, Bruce, M1 aRich, Stephen, S1 aRivadeneira, Fernando1 aRochat, Thierry1 aRotter, Jerome, I1 aArtigas, Maria, Soler1 aStarr, John, M1 aUitterlinden, André, G1 aWareham, Nicholas, J1 aWijmenga, Cisca1 aZanen, Pieter1 aProvince, Michael, A1 aSilverman, Edwin, K1 aDeary, Ian, J1 aPalmer, Lyle, J1 aCassano, Patricia, A1 aGudnason, Vilmundur1 aBarr, Graham1 aLoos, Ruth, J F1 aStrachan, David, P1 aLondon, Stephanie, J1 aBoezen, Marike1 aProbst-Hensch, Nicole1 aGharib, Sina, A1 aHall, Ian, P1 aO'Connor, George, T1 aTobin, Martin, D1 aStricker, Bruno, H uhttps://chs-nhlbi.org/node/609205536nas a2201405 4500008004100000022001400041245012000055210006900175260000900244300001300253490000600266520151700272653002901789653002001818653001801838653003401856653002001890653002301910653001101933653000901944653002601953653003601979653004402015653004302059653002802102653001202130653003002142653001902172100002102191700002602212700002002238700001802258700002102276700002602297700001802323700001902341700001602360700002202376700002102398700002202419700001702441700001602458700001902474700001802493700001902511700002002530700002402550700001902574700002202593700001802615700001702633700002202650700002102672700001802693700001902711700001802730700002002748700001702768700002002785700002202805700002602827700001902853700002202872700002402894700002202918700001902940700002402959700002302983700002203006700002203028700002003050700001903070700002003089700001903109700002103128700001903149700002403168700002303192700002603215700002103241700002803262700001703290700001903307700002003326700002003346700002803366700002003394700002103414700002003435700002403455700001903479700002103498700001903519700002203538700001803560700002803578700002803606700001803634700002303652700001703675700002503692700001903717700002503736700002403761700002903785700002003814700002703834700002303861700002403884700001903908700001703927700002503944700002303969700002003992700001704012700001904029700002104048700002504069856003604094 2012 eng d a1553-740400aGenome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.0 aGenomewide joint metaanalysis of SNP and SNPbysmoking interactio c2012 ae10030980 v83 aGenome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
10aForced Expiratory Volume10aGene Expression10aGenome, Human10aGenome-Wide Association Study10aHLA-DQ Antigens10aHLA-DQ beta-Chains10aHumans10aLung10aNerve Tissue Proteins10aPolymorphism, Single Nucleotide10aPotassium Channels, Inwardly Rectifying10aPulmonary Disease, Chronic Obstructive10aReceptors, Cell Surface10aSmoking10aSOX9 Transcription Factor10aVital Capacity1 aHancock, Dana, B1 aArtigas, Maria, Soler1 aGharib, Sina, A1 aHenry, Amanda1 aManichaikul, Ani1 aRamasamy, Adaikalavan1 aLoth, Daan, W1 aImboden, Medea1 aKoch, Beate1 aMcArdle, Wendy, L1 aSmith, Albert, V1 aSmolonska, Joanna1 aSood, Akshay1 aTang, Wenbo1 aWilk, Jemma, B1 aZhai, Guangju1 aZhao, Jing Hua1 aAschard, Hugues1 aBurkart, Kristin, M1 aCurjuric, Ivan1 aEijgelsheim, Mark1 aElliott, Paul1 aGu, Xiangjun1 aHarris, Tamara, B1 aJanson, Christer1 aHomuth, Georg1 aHysi, Pirro, G1 aLiu, Jason, Z1 aLoehr, Laura, R1 aLohman, Kurt1 aLoos, Ruth, J F1 aManning, Alisa, K1 aMarciante, Kristin, D1 aObeidat, Ma'en1 aPostma, Dirkje, S1 aAldrich, Melinda, C1 aBrusselle, Guy, G1 aChen, Ting-Hsu1 aEiriksdottir, Gudny1 aFranceschini, Nora1 aHeinrich, Joachim1 aRotter, Jerome, I1 aWijmenga, Cisca1 aWilliams, Dale1 aBentley, Amy, R1 aHofman, Albert1 aLaurie, Cathy, C1 aLumley, Thomas1 aMorrison, Alanna, C1 aJoubert, Bonnie, R1 aRivadeneira, Fernando1 aCouper, David, J1 aKritchevsky, Stephen, B1 aLiu, Yongmei1 aWjst, Matthias1 aWain, Louise, V1 aVonk, Judith, M1 aUitterlinden, André, G1 aRochat, Thierry1 aRich, Stephen, S1 aPsaty, Bruce, M1 aO'Connor, George, T1 aNorth, Kari, E1 aMirel, Daniel, B1 aMeibohm, Bernd1 aLauner, Lenore, J1 aKhaw, Kay-Tee1 aHartikainen, Anna-Liisa1 aHammond, Christopher, J1 aGläser, Sven1 aMarchini, Jonathan1 aKraft, Peter1 aWareham, Nicholas, J1 aVölzke, Henry1 aStricker, Bruno, H C1 aSpector, Timothy, D1 aProbst-Hensch, Nicole, M1 aJarvis, Deborah1 aJarvelin, Marjo-Riitta1 aHeckbert, Susan, R1 aGudnason, Vilmundur1 aBoezen, Marike1 aBarr, Graham1 aCassano, Patricia, A1 aStrachan, David, P1 aFornage, Myriam1 aHall, Ian, P1 aDupuis, Josée1 aTobin, Martin, D1 aLondon, Stephanie, J uhttps://chs-nhlbi.org/node/608803017nas a2200493 4500008004100000022001400041245006200055210005700117260001300174300001100187490000700198520168900205653000901894653002401903653001901927653002401946653001101970653001101981653001401992653002102006653000902027653001602036653001702052100002102069700002402090700001902114700002302133700002302156700002202179700002402201700002402225700002502249700001802274700002602292700001902318700001802337700002002355700002202375700002202397700002502419700002002444700002302464856003602487 2013 eng d a1556-387100aThe QT interval and risk of incident atrial fibrillation.0 aQT interval and risk of incident atrial fibrillation c2013 Oct a1562-80 v103 aBACKGROUND: Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine.
OBJECTIVE: To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF.
METHODS: We examined a prolonged QT interval corrected by using the Framingham formula (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas.
RESULTS: Among 14,538 ARIC study participants, a prolonged QT(Fram) predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.42-2.96; P < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QT(Fram) was associated with an increased unadjusted (HR 1.14; 95% CI 1.10-1.17; P < .001) and adjusted (HR 1.11; 95% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts.
CONCLUSIONS: A prolonged QT interval is associated with an increased risk of incident AF.
10aAged10aAtrial Fibrillation10aCohort Studies10aElectrocardiography10aFemale10aHumans10aIncidence10aLong QT Syndrome10aMale10aMiddle Aged10aRisk Factors1 aMandyam, Mala, C1 aSoliman, Elsayed, Z1 aAlonso, Alvaro1 aDewland, Thomas, A1 aHeckbert, Susan, R1 aVittinghoff, Eric1 aCummings, Steven, R1 aEllinor, Patrick, T1 aChaitman, Bernard, R1 aStocke, Karen1 aApplegate, William, B1 aArking, Dan, E1 aButler, Javed1 aLoehr, Laura, R1 aMagnani, Jared, W1 aMurphy, Rachel, A1 aSatterfield, Suzanne1 aNewman, Anne, B1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/599807147nas a2202257 4500008004100000022001400041245010000055210006900155260001300224300001100237490000700248520092000255653001901175653002301194653002201217653002901239653001701268653003801285653001801323653003401341653001101375653001801386653002701404653003601431653001401467653002801481653003101509653001501540653001901555100001801574700002601592700002001618700002001638700002301658700001601681700002301697700002601720700001501746700002101761700002001782700002301802700001901825700002501844700002201869700002601891700002501917700001901942700001801961700001901979700002001998700002202018700001802040700002002058700001702078700002402095700003102119700001902150700001902169700002002188700001502208700001802223700002202241700002002263700002002283700001202303700001902315700001602334700002102350700001902371700002202390700001902412700002402431700001602455700001702471700001902488700002002507700002402527700002002551700001802571700001802589700002102607700002702628700001702655700001702672700002702689700001902716700002202735700001702757700002002774700002102794700001802815700001902833700001902852700002002871700002602891700001902917700001902936700002402955700002402979700002203003700001303025700002203038700002003060700002103080700001903101700001903120700001803139700002003157700002003177700001703197700002503214700002803239700002003267700002303287700002203310700001503332700001803347700002303365700001603388700002603404700001703430700001603447700001703463700001903480700002303499700001903522700002003541700002403561700002003585700002103605700002103626700002103647700002203668700001903690700002003709700002103729700002203750700001903772700002003791700002003811700002203831700001803853700002803871700002403899700001703923700002803940700002403968700002103992700001904013700001904032700002204051700001804073700002204091700001904113700001804132700002304150700002504173700002004198700001904218700002404237700001904261700001604280700001904296700002204315700001804337700001904355700001704374700002704391700002104418700001504439700002304454700002204477700002404499700001704523700002504540700002104565700001704586700001904603700002204622700001704644700002404661700002504685700001704710700002204727700001904749700001704768700002204785700002104807700002504828856003604853 2014 eng d a1546-171800aGenome-wide association analysis identifies six new loci associated with forced vital capacity.0 aGenomewide association analysis identifies six new loci associat c2014 Jul a669-770 v463 aForced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
10aCohort Studies10aDatabases, Genetic10aFollow-Up Studies10aForced Expiratory Volume10aGenetic Loci10aGenetic Predisposition to Disease10aGenome, Human10aGenome-Wide Association Study10aHumans10aLung Diseases10aMeta-Analysis as Topic10aPolymorphism, Single Nucleotide10aPrognosis10aQuantitative Trait Loci10aRespiratory Function Tests10aSpirometry10aVital Capacity1 aLoth, Daan, W1 aArtigas, Maria, Soler1 aGharib, Sina, A1 aWain, Louise, V1 aFranceschini, Nora1 aKoch, Beate1 aPottinger, Tess, D1 aSmith, Albert, Vernon1 aDuan, Qing1 aOldmeadow, Chris1 aLee, Mi, Kyeong1 aStrachan, David, P1 aJames, Alan, L1 aHuffman, Jennifer, E1 aVitart, Veronique1 aRamasamy, Adaikalavan1 aWareham, Nicholas, J1 aKaprio, Jaakko1 aWang, Xin-Qun1 aTrochet, Holly1 aKähönen, Mika1 aFlexeder, Claudia1 aAlbrecht, Eva1 aLopez, Lorna, M1 ade Jong, Kim1 aThyagarajan, Bharat1 aAlves, Alexessander, Couto1 aEnroth, Stefan1 aOmenaas, Ernst1 aJoshi, Peter, K1 aFall, Tove1 aViñuela, Ana1 aLauner, Lenore, J1 aLoehr, Laura, R1 aFornage, Myriam1 aLi, Guo1 aWilk, Jemma, B1 aTang, Wenbo1 aManichaikul, Ani1 aLahousse, Lies1 aHarris, Tamara, B1 aNorth, Kari, E1 aRudnicka, Alicja, R1 aHui, Jennie1 aGu, Xiangjun1 aLumley, Thomas1 aWright, Alan, F1 aHastie, Nicholas, D1 aCampbell, Susan1 aKumar, Rajesh1 aPin, Isabelle1 aScott, Robert, A1 aPietiläinen, Kirsi, H1 aSurakka, Ida1 aLiu, Yongmei1 aHolliday, Elizabeth, G1 aSchulz, Holger1 aHeinrich, Joachim1 aDavies, Gail1 aVonk, Judith, M1 aWojczynski, Mary1 aPouta, Anneli1 aJohansson, Asa1 aWild, Sarah, H1 aIngelsson, Erik1 aRivadeneira, Fernando1 aVölzke, Henry1 aHysi, Pirro, G1 aEiriksdottir, Gudny1 aMorrison, Alanna, C1 aRotter, Jerome, I1 aGao, Wei1 aPostma, Dirkje, S1 aWhite, Wendy, B1 aRich, Stephen, S1 aHofman, Albert1 aAspelund, Thor1 aCouper, David1 aSmith, Lewis, J1 aPsaty, Bruce, M1 aLohman, Kurt1 aBurchard, Esteban, G1 aUitterlinden, André, G1 aGarcia, Melissa1 aJoubert, Bonnie, R1 aMcArdle, Wendy, L1 aMusk, Bill1 aHansel, Nadia1 aHeckbert, Susan, R1 aZgaga, Lina1 avan Meurs, Joyce, B J1 aNavarro, Pau1 aRudan, Igor1 aOh, Yeon-Mok1 aRedline, Susan1 aJarvis, Deborah, L1 aZhao, Jing Hua1 aRantanen, Taina1 aO'Connor, George, T1 aRipatti, Samuli1 aScott, Rodney, J1 aKarrasch, Stefan1 aGrallert, Harald1 aGaddis, Nathan, C1 aStarr, John, M1 aWijmenga, Cisca1 aMinster, Ryan, L1 aLederer, David, J1 aPekkanen, Juha1 aGyllensten, Ulf1 aCampbell, Harry1 aMorris, Andrew, P1 aGläser, Sven1 aHammond, Christopher, J1 aBurkart, Kristin, M1 aBeilby, John1 aKritchevsky, Stephen, B1 aGudnason, Vilmundur1 aHancock, Dana, B1 aWilliams, Dale1 aPolasek, Ozren1 aZemunik, Tatijana1 aKolcic, Ivana1 aPetrini, Marcy, F1 aWjst, Matthias1 aKim, Woo, Jin1 aPorteous, David, J1 aScotland, Generation1 aSmith, Blair, H1 aViljanen, Anne1 aHeliövaara, Markku1 aAttia, John, R1 aSayers, Ian1 aHampel, Regina1 aGieger, Christian1 aDeary, Ian, J1 aBoezen, Marike1 aNewman, Anne1 aJarvelin, Marjo-Riitta1 aWilson, James, F1 aLind, Lars1 aStricker, Bruno, H1 aTeumer, Alexander1 aSpector, Timothy, D1 aMelén, Erik1 aPeters, Marjolein, J1 aLange, Leslie, A1 aBarr, Graham1 aBracke, Ken, R1 aVerhamme, Fien, M1 aSung, Joohon1 aHiemstra, Pieter, S1 aCassano, Patricia, A1 aSood, Akshay1 aHayward, Caroline1 aDupuis, Josée1 aHall, Ian, P1 aBrusselle, Guy, G1 aTobin, Martin, D1 aLondon, Stephanie, J uhttps://chs-nhlbi.org/node/658202780nas a2200445 4500008004100000022001400041245010600055210006900161260001600230300001400246490000800260520149600268100002601764700002201790700002501812700001801837700002101855700002101876700002001897700002101917700001701938700001901955700002101974700001801995700002002013700002502033700002202058700002002080700002402100700002402124700002002148700001402168700001602182700002102198700002402219700002002243700001802263700001702281856003602298 2018 eng d a1476-625600aHarmonization of Respiratory Data From 9 US Population-Based Cohorts: The NHLBI Pooled Cohorts Study.0 aHarmonization of Respiratory Data From 9 US PopulationBased Coho c2018 Nov 01 a2265-22780 v1873 aChronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.
1 aOelsner, Elizabeth, C1 aBalte, Pallavi, P1 aCassano, Patricia, A1 aCouper, David1 aEnright, Paul, L1 aFolsom, Aaron, R1 aHankinson, John1 aJacobs, David, R1 aKalhan, Ravi1 aKaplan, Robert1 aKronmal, Richard1 aLange, Leslie1 aLoehr, Laura, R1 aLondon, Stephanie, J1 aAcien, Ana, Navas1 aNewman, Anne, B1 aO'Connor, George, T1 aSchwartz, Joseph, E1 aSmith, Lewis, J1 aYeh, Fawn1 aZhang, Yiyi1 aMoran, Andrew, E1 aMwasongwe, Stanford1 aWhite, Wendy, B1 aYende, Sachin1 aBarr, Graham uhttps://chs-nhlbi.org/node/804207136nas a2202245 4500008004100000022001400041245011700055210006900172260001300241300001000254490000700264520074900271100002301020700003301043700002401076700002601100700002301126700001301149700001701162700002001179700002101199700001701220700001901237700003201256700002101288700002301309700002301332700002501355700003101380700002101411700002201432700002201454700002401476700001701500700002201517700002101539700003101560700002001591700002001611700001801631700002501649700003101674700002501705700002101730700001701751700002301768700002001791700002101811700002101832700002401853700002201877700001801899700001901917700002001936700001801956700001801974700002001992700002102012700002002033700002402053700002802077700001902105700002302124700001902147700002202166700002402188700002002212700002102232700002002253700002402273700001902297700001802316700002002334700002202354700001602376700001902392700002102411700002502432700001602457700002102473700002702494700002002521700001802541700002502559700002202584700002102606700002002627700002102647700002602668700002402694700002502718700002402743700001902767700001902786700001802805700001802823700002102841700001902862700002002881700002302901700001802924700001702942700001802959700002202977700002302999700002103022700001203043700001803055700002003073700002503093700001803118700002103136700002003157700002603177700002503203700002303228700002103251700001803272700002203290700001703312700001703329700002003346700001703366700002003383700002003403700002103423700003003444700001903474700002403493700002603517700002303543700001903566700001903585700002203604700002203626700002203648700002203670700002603692700002303718700002203741700002303763700002603786700002103812700002403833700002103857700002303878700002003901700002203921700001803943700002603961700002203987700002004009700002104029700002004050700002204070700001804092700002104110700002304131700002304154700002304177700002404200700002504224700002804249700002404277700002304301700002304324700002804347700002804375700001904403700002204422700002104444700002204465700002004487700002004507700002104527700002004548700002004568700002004588700002104608700002304629700002004652700002104672700001904693700001904712700002304731700001704754700002004771710006304791856003604854 2018 eng d a1546-171800aMultiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.0 aMultiancestry association study identifies new asthma risk loci c2018 Jan a42-530 v503 aWe examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.
1 aDemenais, Florence1 aMargaritte-Jeannin, Patricia1 aBarnes, Kathleen, C1 aCookson, William, O C1 aAltmüller, Janine1 aAng, Wei1 aBarr, Graham1 aBeaty, Terri, H1 aBecker, Allan, B1 aBeilby, John1 aBisgaard, Hans1 aBjornsdottir, Unnur, Steina1 aBleecker, Eugene1 aBønnelykke, Klaus1 aBoomsma, Dorret, I1 aBouzigon, Emmanuelle1 aBrightling, Christopher, E1 aBrossard, Myriam1 aBrusselle, Guy, G1 aBurchard, Esteban1 aBurkart, Kristin, M1 aBush, Andrew1 aChan-Yeung, Moira1 aChung, Kian, Fan1 aAlves, Alexessander, Couto1 aCurtin, John, A1 aCustovic, Adnan1 aDaley, Denise1 ade Jongste, Johan, C1 aDel-Rio-Navarro, Blanca, E1 aDonohue, Kathleen, M1 aDuijts, Liesbeth1 aEng, Celeste1 aEriksson, Johan, G1 aFarrall, Martin1 aFedorova, Yuliya1 aFeenstra, Bjarke1 aFerreira, Manuel, A1 aFreidin, Maxim, B1 aGajdos, Zofia1 aGauderman, Jim1 aGehring, Ulrike1 aGeller, Frank1 aGenuneit, Jon1 aGharib, Sina, A1 aGilliland, Frank1 aGranell, Raquel1 aGraves, Penelope, E1 aGudbjartsson, Daniel, F1 aHaahtela, Tari1 aHeckbert, Susan, R1 aHeederik, Dick1 aHeinrich, Joachim1 aHeliövaara, Markku1 aHenderson, John1 aHimes, Blanca, E1 aHirose, Hiroshi1 aHirschhorn, Joel, N1 aHofman, Albert1 aHolt, Patrick1 aHottenga, Jouke1 aHudson, Thomas, J1 aHui, Jennie1 aImboden, Medea1 aIvanov, Vladimir1 aJaddoe, Vincent, W V1 aJames, Alan1 aJanson, Christer1 aJarvelin, Marjo-Riitta1 aJarvis, Deborah1 aJones, Graham1 aJonsdottir, Ingileif1 aJousilahti, Pekka1 aKabesch, Michael1 aKähönen, Mika1 aKantor, David, B1 aKarunas, Alexandra, S1 aKhusnutdinova, Elza1 aKoppelman, Gerard, H1 aKozyrskyj, Anita, L1 aKreiner, Eskil1 aKubo, Michiaki1 aKumar, Rajesh1 aKumar, Ashish1 aKuokkanen, Mikko1 aLahousse, Lies1 aLaitinen, Tarja1 aLaprise, Catherine1 aLathrop, Mark1 aLau, Susanne1 aLee, Young-Ae1 aLehtimäki, Terho1 aLetort, Sébastien1 aLevin, Albert, M1 aLi, Guo1 aLiang, Liming1 aLoehr, Laura, R1 aLondon, Stephanie, J1 aLoth, Daan, W1 aManichaikul, Ani1 aMarenholz, Ingo1 aMartinez, Fernando, J1 aMatheson, Melanie, C1 aMathias, Rasika, A1 aMatsumoto, Kenji1 aMbarek, Hamdi1 aMcArdle, Wendy, L1 aMelbye, Mads1 aMelén, Erik1 aMeyers, Deborah1 aMichel, Sven1 aMohamdi, Hamida1 aMusk, Arthur, W1 aMyers, Rachel, A1 aNieuwenhuis, Maartje, A E1 aNoguchi, Emiko1 aO'Connor, George, T1 aOgorodova, Ludmila, M1 aPalmer, Cameron, D1 aPalotie, Aarno1 aPark, Julie, E1 aPennell, Craig, E1 aPershagen, Göran1 aPolonikov, Alexey1 aPostma, Dirkje, S1 aProbst-Hensch, Nicole1 aPuzyrev, Valery, P1 aRaby, Benjamin, A1 aRaitakari, Olli, T1 aRamasamy, Adaikalavan1 aRich, Stephen, S1 aRobertson, Colin, F1 aRomieu, Isabelle1 aSalam, Muhammad, T1 aSalomaa, Veikko1 aSchlünssen, Vivi1 aScott, Robert1 aSelivanova, Polina, A1 aSigsgaard, Torben1 aSimpson, Angela1 aSiroux, Valérie1 aSmith, Lewis, J1 aSolodilova, Maria1 aStandl, Marie1 aStefansson, Kari1 aStrachan, David, P1 aStricker, Bruno, H1 aTakahashi, Atsushi1 aThompson, Philip, J1 aThorleifsson, Gudmar1 aThorsteinsdottir, Unnur1 aTiesler, Carla, M T1 aTorgerson, Dara, G1 aTsunoda, Tatsuhiko1 aUitterlinden, André, G1 avan der Valk, Ralf, J P1 aVaysse, Amaury1 aVedantam, Sailaja1 avon Berg, Andrea1 avon Mutius, Erika1 aVonk, Judith, M1 aWaage, Johannes1 aWareham, Nick, J1 aWeiss, Scott, T1 aWhite, Wendy, B1 aWickman, Magnus1 aWiden, Elisabeth1 aWillemsen, Gonneke1 aWilliams, Keoki1 aWouters, Inge, M1 aYang, James, J1 aZhao, Jing Hua1 aMoffatt, Miriam, F1 aOber, Carole1 aNicolae, Dan, L1 aAustralian Asthma Genetics Consortium (AAGC) collaborators uhttps://chs-nhlbi.org/node/755803207nas a2200337 4500008004100000022001400041245013200055210006900187260001600256300001200272490000800284520218000292100002602472700002202498700002102520700002502541700002102566700001702587700002402604700001702628700002102645700002002666700002402686700002402710700002102734700002202755700002102777700001702798700001802815856003602833 2019 eng d a1535-497000aAlbuminuria, Lung Function Decline, and Risk of Incident Chronic Obstructive Pulmonary Disease. The NHLBI Pooled Cohorts Study.0 aAlbuminuria Lung Function Decline and Risk of Incident Chronic O c2019 Feb 01 a321-3320 v1993 aRATIONALE: Chronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD.
OBJECTIVES: To test whether albuminuria was associated with lung function decline and incident CLRDs.
METHODS: Six U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications.
MEASUREMENTS AND MAIN RESULTS: Among 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P < 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease.
CONCLUSIONS: Albuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population-based sample.
1 aOelsner, Elizabeth, C1 aBalte, Pallavi, P1 aGrams, Morgan, E1 aCassano, Patricia, A1 aJacobs, David, R1 aBarr, Graham1 aBurkart, Kristin, M1 aKalhan, Ravi1 aKronmal, Richard1 aLoehr, Laura, R1 aO'Connor, George, T1 aSchwartz, Joseph, E1 aShlipak, Michael1 aTracy, Russell, P1 aTsai, Michael, Y1 aWhite, Wendy1 aYende, Sachin uhttps://chs-nhlbi.org/node/798004942nas a2200529 4500008004100000022001400041245009700055210006900152260001500221300001200236490000800248520351200256653001503768653001003783653000903793653002203802653001103824653002403835653001103859653001103870653000903881653000903890653001603899653002403915653003103939653001203970653001203982653001603994100002204010700002304032700002104055700001804076700002104094700001704115700002404132700002004156700002504176700002004201700002404221700002404245700002304269700002004292700002004312700001804332700002604350856003604376 2020 eng d a2168-611400aAssociation of Nonobstructive Chronic Bronchitis With Respiratory Health Outcomes in Adults.0 aAssociation of Nonobstructive Chronic Bronchitis With Respirator c2020 05 01 a676-6860 v1803 aImportance: Chronic bronchitis has been associated with cigarette smoking as well as with e-cigarette use among young adults, but the association of chronic bronchitis in persons without airflow obstruction or clinical asthma, described as nonobstructive chronic bronchitis, with respiratory health outcomes remains uncertain.
Objective: To assess whether nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes in adult ever smokers and never smokers.
Design, Setting, and Participants: This prospective cohort study included 22 325 adults without initial airflow obstruction (defined as the ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity [FVC] of <0.70) or clinical asthma at baseline. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 9 US general population-based cohorts. Thus present study is based on data from 5 of these cohorts. Participants were enrolled from August 1971 through May 2007 and were followed up through December 2018.
Exposures: Nonobstructive chronic bronchitis was defined by questionnaire at baseline as both cough and phlegm for at least 3 months for at least 2 consecutive years.
Main Outcomes and Measures: Lung function was measured by prebronchodilator spirometry. Hospitalizations and deaths due to chronic lower respiratory disease and respiratory disease-related mortality were defined by events adjudication and administrative criteria. Models were stratified by smoking status and adjusted for anthropometric, sociodemographic, and smoking-related factors. The comparison group was participants without nonobstructive chronic bronchitis.
Results: Among 22 325 adults included in the analysis, mean (SD) age was 53.0 (16.3) years (range, 18.0-95.0 years), 58.2% were female, 65.9% were non-Hispanic white, and 49.6% were ever smokers. Among 11 082 ever smokers with 99 869 person-years of follow-up, participants with nonobstructive chronic bronchitis (300 [2.7%]) had accelerated decreases in FEV1 (4.1 mL/y; 95% CI, 2.1-6.1 mL/y) and FVC (4.7 mL/y; 95% CI, 2.2-7.2 mL/y), increased risks of chronic lower respiratory disease-related hospitalization or mortality (hazard ratio [HR], 2.2; 95% CI, 1.7-2.7), and greater respiratory disease-related (HR, 2.0; 95% CI, 1.1-3.8) and all-cause mortality (HR, 1.5; 95% CI, 1.3-1.8) compared with ever smokers without nonobstructive chronic bronchitis. Among 11 243 never smokers with 120 004 person-years of follow-up, participants with nonobstructive chronic bronchitis (151 [1.3%]) had greater rates of chronic lower respiratory disease-related hospitalization or mortality (HR, 3.1; 95% CI, 2.1-4.5) compared with never smokers without nonobstructive chronic bronchitis. Nonobstructive chronic bronchitis was not associated with FEV1:FVC decline or incident airflow obstruction. The presence of at least 1 of the component symptoms of nonobstructive chronic bronchitis (ie, chronic cough or phlegm), which was common in both ever smokers (11.0%) and never smokers (6.7%), was associated with adverse respiratory health outcomes.
Conclusions and Relevance: The findings suggest that nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes, particularly in ever smokers, and may be a high-risk phenotype suitable for risk stratification and targeted therapies.
10aAdolescent10aAdult10aAged10aAged, 80 and over10aAsthma10aBronchitis, Chronic10aFemale10aHumans10aLung10aMale10aMiddle Aged10aProspective Studies10aRespiratory Function Tests10aSmokers10aSmoking10aYoung Adult1 aBalte, Pallavi, P1 aChaves, Paulo, H M1 aCouper, David, J1 aEnright, Paul1 aJacobs, David, R1 aKalhan, Ravi1 aKronmal, Richard, A1 aLoehr, Laura, R1 aLondon, Stephanie, J1 aNewman, Anne, B1 aO'Connor, George, T1 aSchwartz, Joseph, E1 aSmith, Benjamin, M1 aSmith, Lewis, J1 aWhite, Wendy, B1 aYende, Sachin1 aOelsner, Elizabeth, C uhttps://chs-nhlbi.org/node/862004670nas a2200577 4500008004100000022001400041245014000055210006900195260001200264300001000276490000600286520303600292653001003328653000903338653002503347653001503372653001103387653002203398653001103420653000903431653000903440653001603449653005303465653001603518653004003534653001203574653001203586653001503598653001803613653001603631100002603647700002203673700002003695700002503715700001803740700002103758700002203779700002103801700001703822700002203839700002403861700002003885700002503905700002003930700002403950700002403974700002003998700002004018700001804038856003604056 2020 eng d a2213-261900aLung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI Pooled Cohorts Study.0 aLung function decline in former smokers and lowintensity current c2020 01 a34-440 v83 aBACKGROUND: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease.
METHODS: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (≥17 years), two recruited middle-aged and older adults (≥45 years), and two recruited only elderly adults (≥65 years) with examinations done between 1983 and 2014. FEV decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption.
FINDINGS: 25 352 participants (ages 17-93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3-20), FEV decline at the median age (57 years) was 31·01 mL per year (95% CI 30·66-31·37) in sustained never-smokers, 34·97 mL per year (34·36-35·57) in former smokers, and 39·92 mL per year (38·92-40·92) in current smokers. With adjustment, former smokers showed an accelerated FEV decline of 1·82 mL per year (95% CI 1·24-2·40) compared to never-smokers, which was approximately 20% of the effect estimate for current smokers (9·21 mL per year; 95% CI 8·35-10·08). Compared to never-smokers, accelerated FEV decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (<10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV decline in current smokers consuming less than five cigarettes per day (7·65 mL per year; 95% CI 6·21-9·09) was 68% of that in current smokers consuming 30 or more cigarettes per day (11·24 mL per year; 9·86-12·62), and around five times greater than in former smokers (1·57 mL per year; 1·00-2·14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results.
INTERPRETATION: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage.
FUNDING: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency.
10aAdult10aAged10aCase-Control Studies10aEx-Smokers10aFemale10aFollow-Up Studies10aHumans10aLung10aMale10aMiddle Aged10aNational Heart, Lung, and Blood Institute (U.S.)10aNon-Smokers10aRespiratory Physiological Phenomena10aSmokers10aSmoking10aSpirometry10aUnited States10aYoung Adult1 aOelsner, Elizabeth, C1 aBalte, Pallavi, P1 aBhatt, Surya, P1 aCassano, Patricia, A1 aCouper, David1 aFolsom, Aaron, R1 aFreedman, Neal, D1 aJacobs, David, R1 aKalhan, Ravi1 aMathew, Amanda, R1 aKronmal, Richard, A1 aLoehr, Laura, R1 aLondon, Stephanie, J1 aNewman, Anne, B1 aO'Connor, George, T1 aSchwartz, Joseph, E1 aSmith, Lewis, J1 aWhite, Wendy, B1 aYende, Sachin uhttps://chs-nhlbi.org/node/840204776nas a2201261 4500008004100000022001400041245010300055210006900158260001500227300000900242490000700251520104900258653001001307653002201317653000901339653002201348653005001370653002901420653002401449653001101473653002201484653001701506653003801523653003401561653001101595653005001606653000901656653000901665653001601674653003601690653004101726653004301767653004001810653004601850653002801896100001701924700001601941700001801957700001801975700001501993700001502008700001702023700001902040700001702059700003002076700002902106700002202135700002302157700001302180700002102193700001902214700001902233700001502252700002002267700001902287700002302306700002002329700002502349700002002374700002002394700002402414700002002438700002702458700002102485700002002506700001702526700001902543700002002562700001702582700001702599700002202616700002302638700002002661700002502681700002802706700002202734700002402756700001702780700002602797700002002823700002302843700003102866700002502897700001902922700002002941700002102961700002402982700001903006700002003025700002103045700002403066700002503090700002403115700002203139700002003161700002103181700002503202700002303227700002603250700002503276700002403301700001703325700002003342700002103362710006503383710003003448856003603478 2020 eng d a2041-172300aWhole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants.0 aWhole genome sequence analysis of pulmonary function and COPD in c2020 10 14 a51820 v113 aChronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry.
10aAdult10aAfrican Americans10aAged10aAged, 80 and over10aAlpha-Ketoglutarate-Dependent Dioxygenase FTO10aCalcium-Binding Proteins10aFeasibility Studies10aFemale10aFollow-Up Studies10aGenetic Loci10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aIntracellular Signaling Peptides and Proteins10aLung10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aProtein Inhibitors of Activated STAT10aPulmonary Disease, Chronic Obstructive10aRespiratory Physiological Phenomena10aSmall Ubiquitin-Related Modifier Proteins10aWhole Genome Sequencing1 aZhao, Xutong1 aQiao, Dandi1 aYang, Chaojie1 aKasela, Silva1 aKim, Wonji1 aMa, Yanlin1 aShrine, Nick1 aBatini, Chiara1 aSofer, Tamar1 aTaliun, Sarah, A Gagliano1 aSakornsakolpat, Phuwanat1 aBalte, Pallavi, P1 aProkopenko, Dmitry1 aYu, Bing1 aLange, Leslie, A1 aDupuis, Josée1 aCade, Brian, E1 aLee, Jiwon1 aGharib, Sina, A1 aDaya, Michelle1 aLaurie, Cecelia, A1 aRuczinski, Ingo1 aCupples, Adrienne, L1 aLoehr, Laura, R1 aBartz, Traci, M1 aMorrison, Alanna, C1 aPsaty, Bruce, M1 aVasan, Ramachandran, S1 aWilson, James, G1 aTaylor, Kent, D1 aDurda, Peter1 aJohnson, Craig1 aCornell, Elaine1 aGuo, Xiuqing1 aLiu, Yongmei1 aTracy, Russell, P1 aArdlie, Kristin, G1 aAguet, Francois1 aVanDenBerg, David, J1 aPapanicolaou, George, J1 aRotter, Jerome, I1 aBarnes, Kathleen, C1 aJain, Deepti1 aNickerson, Deborah, A1 aMuzny, Donna, M1 aMetcalf, Ginger, A1 aDoddapaneni, Harshavardhan1 aDugan-Perez, Shannon1 aGupta, Namrata1 aGabriel, Stacey1 aRich, Stephen, S1 aO'Connor, George, T1 aRedline, Susan1 aReed, Robert, M1 aLaurie, Cathy, C1 aDaviglus, Martha, L1 aPreudhomme, Liana, K1 aBurkart, Kristin, M1 aKaplan, Robert, C1 aWain, Louise, V1 aTobin, Martin, D1 aLondon, Stephanie, J1 aLappalainen, Tuuli1 aOelsner, Elizabeth, C1 aAbecasis, Goncalo, R1 aSilverman, Edwin, K1 aBarr, Graham1 aCho, Michael, H1 aManichaikul, Ani1 aNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium1 aTOPMed Lung Working Group uhttps://chs-nhlbi.org/node/863903962nas a2200733 4500008004100000022001400041245014300055210006900198260001600267520182100283100001602104700001602120700001502136700001802151700002202169700002102191700002002212700001802232700001602250700001302266700001902279700002302298700001702321700002002338700002602358700002002384700002302404700003102427700001902458700001902477700002502496700002502521700002002546700001702566700002202583700002102605700002002626700002002646700002402666700002702690700001902717700002102736700002402757700002102781700002202802700001702824700001902841700002002860700002002880700001902900700001902919700002502938700002302963700002602986700002403012700001703036700002503053700002403078700002003102700001903122700002103141710003003162856003603192 2022 eng d a1537-660500aPolygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program.0 aPolygenic transcriptome risk scores for COPD and lung function i c2022 Mar 313 aWhile polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV] and its ratio to forced vital capacity [FEV/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV and FEV/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08-1.43] for PTRS versus 1.10 [0.96-1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p < 2.2 × 10 with portability gains ranging from 5% to 28%) for both dichotomous COPD traits and across all smoking strata. Our study demonstrates the value of PTRS for improved cross-ethnic portability compared to PRS in predicting COPD risk.
1 aHu, Xiaowei1 aQiao, Dandi1 aKim, Wonji1 aMoll, Matthew1 aBalte, Pallavi, P1 aLange, Leslie, A1 aBartz, Traci, M1 aKumar, Rajesh1 aLi, Xingnan1 aYu, Bing1 aCade, Brian, E1 aLaurie, Cecelia, A1 aSofer, Tamar1 aRuczinski, Ingo1 aNickerson, Deborah, A1 aMuzny, Donna, M1 aMetcalf, Ginger, A1 aDoddapaneni, Harshavardhan1 aGabriel, Stacy1 aGupta, Namrata1 aDugan-Perez, Shannon1 aCupples, Adrienne, L1 aLoehr, Laura, R1 aJain, Deepti1 aRotter, Jerome, I1 aWilson, James, G1 aPsaty, Bruce, M1 aFornage, Myriam1 aMorrison, Alanna, C1 aVasan, Ramachandran, S1 aWashko, George1 aRich, Stephen, S1 aO'Connor, George, T1 aBleecker, Eugene1 aKaplan, Robert, C1 aKalhan, Ravi1 aRedline, Susan1 aGharib, Sina, A1 aMeyers, Deborah1 aOrtega, Victor1 aDupuis, Josée1 aLondon, Stephanie, J1 aLappalainen, Tuuli1 aOelsner, Elizabeth, C1 aSilverman, Edwin, K1 aBarr, Graham1 aThornton, Timothy, A1 aWheeler, Heather, E1 aCho, Michael, H1 aIm, Hae, Kyung1 aManichaikul, Ani1 aTOPMed Lung Working Group uhttps://chs-nhlbi.org/node/9037