05089nas a2201429 4500008004100000022001400041245009100055210006900146260000900215300000600224490000600230520111900236100002501355700002601380700002001406700002101426700002001447700002001467700001901487700002501506700001301531700002001544700002301564700002501587700002801612700001801640700001201658700002401670700002101694700002101715700002101736700002301757700002001780700002401800700002001824700001901844700001901863700002201882700001601904700002801920700002401948700002301972700002401995700002302019700001802042700001602060700001602076700001702092700001602109700001702125700002302142700002502165700002102190700002102211700001802232700002102250700002502271700002002296700001702316700002402333700002602357700002202383700001902405700001502424700002202439700001802461700001802479700002002497700001902517700002002536700002302556700001202579700002002591700002802611700001702639700001602656700002402672700001902696700001902715700001902734700002102753700001902774700002102793700002902814700001902843700002002862700002802882700001802910700002302928700002402951700001902975700002002994700001603014700002003030700002403050700001903074700002203093700001903115700002403134700002103158700002403179700002203203700001603225700001803241700001703259700002303276700002003299700002203319700002003341700002603361700001803387700002403405700002203429700002303451700001903474700002403493700001703517700002103534700002503555710004303580856003603623 2018 eng d a2398-502X00aMeta-analysis of exome array data identifies six novel genetic loci for lung function.0 aMetaanalysis of exome array data identifies six novel genetic lo c2018 a40 v33 a
Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV ), forced vital capacity (FVC) and the ratio of FEV to FVC (FEV /FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. We identified significant (P<2·8x10 ) associations with six SNPs: a nonsynonymous variant in , which is predicted to be damaging, three intronic SNPs ( and ) and two intergenic SNPs near to and Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including and . Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
1 aJackson, Victoria, E1 aLatourelle, Jeanne, C1 aWain, Louise, V1 aSmith, Albert, V1 aGrove, Megan, L1 aBartz, Traci, M1 aObeidat, Ma'en1 aProvince, Michael, A1 aGao, Wei1 aQaiser, Beenish1 aPorteous, David, J1 aCassano, Patricia, A1 aAhluwalia, Tarunveer, S1 aGrarup, Niels1 aLi, Jin1 aAltmaier, Elisabeth1 aMarten, Jonathan1 aHarris, Sarah, E1 aManichaikul, Ani1 aPottinger, Tess, D1 aLi-Gao, Ruifang1 aLind-Thomsen, Allan1 aMahajan, Anubha1 aLahousse, Lies1 aImboden, Medea1 aTeumer, Alexander1 aPrins, Bram1 aLyytikäinen, Leo-Pekka1 aEiriksdottir, Gudny1 aFranceschini, Nora1 aSitlani, Colleen, M1 aBrody, Jennifer, A1 aBossé, Yohan1 aTimens, Wim1 aKraja, Aldi1 aLoukola, Anu1 aTang, Wenbo1 aLiu, Yongmei1 aBork-Jensen, Jette1 aJustesen, Johanne, M1 aLinneberg, Allan1 aLange, Leslie, A1 aRawal, Rajesh1 aKarrasch, Stefan1 aHuffman, Jennifer, E1 aSmith, Blair, H1 aDavies, Gail1 aBurkart, Kristin, M1 aMychaleckyj, Josyf, C1 aBonten, Tobias, N1 aEnroth, Stefan1 aLind, Lars1 aBrusselle, Guy, G1 aKumar, Ashish1 aStubbe, Beate1 aKähönen, Mika1 aWyss, Annah, B1 aPsaty, Bruce, M1 aHeckbert, Susan, R1 aHao, Ke1 aRantanen, Taina1 aKritchevsky, Stephen, B1 aLohman, Kurt1 aSkaaby, Tea1 aPisinger, Charlotta1 aHansen, Torben1 aSchulz, Holger1 aPolasek, Ozren1 aCampbell, Archie1 aStarr, John, M1 aRich, Stephen, S1 aMook-Kanamori, Dennis, O1 aJohansson, Asa1 aIngelsson, Erik1 aUitterlinden, André, G1 aWeiss, Stefan1 aRaitakari, Olli, T1 aGudnason, Vilmundur1 aNorth, Kari, E1 aGharib, Sina, A1 aSin, Don, D1 aTaylor, Kent, D1 aO'Connor, George, T1 aKaprio, Jaakko1 aHarris, Tamara, B1 aPederson, Oluf1 aVestergaard, Henrik1 aWilson, James, G1 aStrauch, Konstantin1 aHayward, Caroline1 aKerr, Shona1 aDeary, Ian, J1 aBarr, Graham1 ade Mutsert, Renée1 aGyllensten, Ulf1 aMorris, Andrew, P1 aIkram, Arfan, M1 aProbst-Hensch, Nicole1 aGläser, Sven1 aZeggini, Eleftheria1 aLehtimäki, Terho1 aStrachan, David, P1 aDupuis, Josée1 aMorrison, Alanna, C1 aHall, Ian, P1 aTobin, Martin, D1 aLondon, Stephanie, J1 aUnderstanding Society Scientific Group uhttps://chs-nhlbi.org/node/7795