06392nas a2201669 4500008004100000022001400041245009700055210006900152260001600221300001200237490000700249520182200256653001002078653002202088653000902110653001202119653003702131653002002168653002602188653001702214653002102231653001802252653004002270653001102310653001902321653001102340653000902351653001602360653001202376653003602388653001302424100001402437700002802451700002002479700002002499700002002519700001902539700002102558700001902579700002002598700001802618700002302636700001802659700001802677700001602695700002402711700001202735700003202747700002302779700001502802700001902817700002002836700001902856700002502875700001702900700002302917700002202940700002302962700002202985700001503007700002503022700002703047700002003074700002203094700002403116700001203140700002103152700002103173700002103194700002503215700001903240700002003259700001903279700002603298700002103324700001703345700002403362700001703386700002303403700002103426700001603447700001803463700002503481700002003506700002003526700002103546700001903567700002303586700001903609700002403628700002303652700002203675700001803697700001803715700002303733700001703756700001203773700001703785700002003802700001703822700001903839700002503858700001603883700001903899700002003918700002003938700002303958700002203981700002804003700002504031700002104056700001604077700001804093700002404111700001504135700002904150700002404179700002504203700003004228700001504258700002004273700001704293700001804310700002204328700002004350700002304370700002104393700002104414700002004435700002504455700002004480700002504500700001404525700002304539700002004562700002904582700001704611700002004628700002704648700001104675856003604686 2014 eng d a1460-208300aFTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.0 aFTO genetic variants dietary intake and body mass index insights c2014 Dec 20 a6961-720 v233 a
FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
10aAdult10aAfrican Americans10aAged10aAlleles10aAsian Continental Ancestry Group10aBody Mass Index10aDietary Carbohydrates10aDietary Fats10aDietary Proteins10aEnergy Intake10aEuropean Continental Ancestry Group10aFemale10aGene Frequency10aHumans10aMale10aMiddle Aged10aObesity10aPolymorphism, Single Nucleotide10aProteins1 aQi, Qibin1 aKilpeläinen, Tuomas, O1 aDowner, Mary, K1 aTanaka, Toshiko1 aSmith, Caren, E1 aSluijs, Ivonne1 aSonestedt, Emily1 aChu, Audrey, Y1 aRenstrom, Frida1 aLin, Xiaochen1 aÄngquist, Lars, H1 aHuang, Jinyan1 aLiu, Zhonghua1 aLi, Yanping1 aAli, Muhammad, Asif1 aXu, Min1 aAhluwalia, Tarunveer, Singh1 aBoer, Jolanda, M A1 aChen, Peng1 aDaimon, Makoto1 aEriksson, Johan1 aPerola, Markus1 aFriedlander, Yechiel1 aGao, Yu-Tang1 aHeppe, Denise, H M1 aHolloway, John, W1 aHouston, Denise, K1 aKanoni, Stavroula1 aKim, Yu-Mi1 aLaaksonen, Maarit, A1 aJääskeläinen, Tiina1 aLee, Nanette, R1 aLehtimäki, Terho1 aLemaitre, Rozenn, N1 aLu, Wei1 aLuben, Robert, N1 aManichaikul, Ani1 aMännistö, Satu1 aMarques-Vidal, Pedro1 aMonda, Keri, L1 aNgwa, Julius, S1 aPerusse, Louis1 avan Rooij, Frank, J A1 aXiang, Yong-Bing1 aWen, Wanqing1 aWojczynski, Mary, K1 aZhu, Jingwen1 aBorecki, Ingrid, B1 aBouchard, Claude1 aCai, Qiuyin1 aCooper, Cyrus1 aDedoussis, George, V1 aDeloukas, Panos1 aFerrucci, Luigi1 aForouhi, Nita, G1 aHansen, Torben1 aChristiansen, Lene1 aHofman, Albert1 aJohansson, Ingegerd1 aJørgensen, Torben1 aKarasawa, Shigeru1 aKhaw, Kay-Tee1 aKim, Mi-Kyung1 aKristiansson, Kati1 aLi, Huaixing1 aLin, Xu1 aLiu, Yongmei1 aLohman, Kurt, K1 aLong, Jirong1 aMikkilä, Vera1 aMozaffarian, Dariush1 aNorth, Kari1 aPedersen, Oluf1 aRaitakari, Olli1 aRissanen, Harri1 aTuomilehto, Jaakko1 aSchouw, Yvonne, T1 aUitterlinden, André, G1 aZillikens, Carola, M1 aFranco, Oscar, H1 aTai, Shyong1 aShu, Xiao, Ou1 aSiscovick, David, S1 aToft, Ulla1 aVerschuren, W, M Monique1 aVollenweider, Peter1 aWareham, Nicholas, J1 aWitteman, Jacqueline, C M1 aZheng, Wei1 aRidker, Paul, M1 aKang, Jae, H1 aLiang, Liming1 aJensen, Majken, K1 aCurhan, Gary, C1 aPasquale, Louis, R1 aHunter, David, J1 aMohlke, Karen, L1 aUusitupa, Matti1 aCupples, Adrienne, L1 aRankinen, Tuomo1 aOrho-Melander, Marju1 aWang, Tao1 aChasman, Daniel, I1 aFranks, Paul, W1 aSørensen, Thorkild, I A1 aHu, Frank, B1 aLoos, Ruth, J F1 aNettleton, Jennifer, A1 aQi, Lu uhttps://chs-nhlbi.org/node/693804825nas a2201141 4500008004100000022001400041245010700055210007000162260001600232300001200248490000700260520164000267653001001907653002001917653002501937653001801962653002301980653004002003653001102043653001702054653003402071653001102105653000902116653001202125653003602137100002702173700002002200700002002220700002002240700001902260700002002279700002402299700002002323700002402343700002302367700002402390700002302414700002402437700001402461700002102475700002102496700002202517700001802539700001902557700001902576700002402595700001902619700002302638700002402661700002002685700001702705700001602722700001702738700002502755700001502780700001802795700001902813700002002832700001402852700002002866700002102886700002102907700002102928700001602949700002002965700002102985700002603006700002003032700001703052700002003069700001803089700001903107700001903126700001903145700002303164700001903187700002803206700002403234700002103258700002503279700002003304700002303324700001603347700002803363700002303391700002503414700001103439700002003450700002503470700002503495700002003520700002203540700002003562700002503582700002003607700002003627856003603647 2015 eng d a1460-208300aGene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.0 aGene × dietary pattern interactions in obesity analysis of up to c2015 Aug 15 a4728-380 v243 aObesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.
10aAdult10aBody Mass Index10aCase-Control Studies10aDiet, Western10aEpistasis, Genetic10aEuropean Continental Ancestry Group10aFemale10aGenetic Loci10aGenome-Wide Association Study10aHumans10aMale10aObesity10aPolymorphism, Single Nucleotide1 aNettleton, Jennifer, A1 aFollis, Jack, L1 aNgwa, Julius, S1 aSmith, Caren, E1 aAhmad, Shafqat1 aTanaka, Toshiko1 aWojczynski, Mary, K1 aVoortman, Trudy1 aLemaitre, Rozenn, N1 aKristiansson, Kati1 aNuotio, Marja-Liisa1 aHouston, Denise, K1 aPerälä, Mia-Maria1 aQi, Qibin1 aSonestedt, Emily1 aManichaikul, Ani1 aKanoni, Stavroula1 aGanna, Andrea1 aMikkilä, Vera1 aNorth, Kari, E1 aSiscovick, David, S1 aHarald, Kennet1 aMcKeown, Nicola, M1 aJohansson, Ingegerd1 aRissanen, Harri1 aLiu, Yongmei1 aLahti, Jari1 aHu, Frank, B1 aBandinelli, Stefania1 aRukh, Gull1 aRich, Stephen1 aBooij, Lisanne1 aDmitriou, Maria1 aAx, Erika1 aRaitakari, Olli1 aMukamal, Kenneth1 aMännistö, Satu1 aHallmans, Göran1 aJula, Antti1 aEricson, Ulrika1 aJacobs, David, R1 avan Rooij, Frank, J A1 aDeloukas, Panos1 aSjogren, Per1 aKähönen, Mika1 aDjoussé, Luc1 aPerola, Markus1 aBarroso, Inês1 aHofman, Albert1 aStirrups, Kathleen1 aViikari, Jorma1 aUitterlinden, André, G1 aKalafati, Ioanna, P1 aFranco, Oscar, H1 aMozaffarian, Dariush1 aSalomaa, Veikko1 aBorecki, Ingrid, B1 aKnekt, Paul1 aKritchevsky, Stephen, B1 aEriksson, Johan, G1 aDedoussis, George, V1 aQi, Lu1 aFerrucci, Luigi1 aOrho-Melander, Marju1 aZillikens, Carola, M1 aIngelsson, Erik1 aLehtimäki, Terho1 aRenstrom, Frida1 aCupples, Adrienne, L1 aLoos, Ruth, J F1 aFranks, Paul, W uhttps://chs-nhlbi.org/node/680205076nas a2201081 4500008004100000022001400041245010500055210006900160260000900229300001300238490000700251520207300258653001002331653000902341653001902350653002602369653002602395653001102421653004002432653001102472653003402483653001102517653000902528653001602537653001202553653001802565100002502583700002202608700002402630700001902654700002702673700002102700700002302721700001802744700001602762700002302778700002502801700002602826700002102852700002202873700001902895700002002914700002902934700001102963700001702974700001802991700002203009700001903031700001903050700002003069700001603089700002003105700002103125700002103146700002003167700001603187700002103203700002403224700001903248700001703267700001903284700002003303700002003323700002103343700002103364700003203385700001903417700002803436700002403464700002003488700001903508700002103527700002203548700002003570700001903590700002103609700002003630700001603650700002103666700002303687700002503710700002303735700002803758700002503786700002103811700002103832700002003853700002203873700002303895700002003918700002003938856003603958 2017 eng d a1932-620300aGenome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.0 aGenomewide association metaanalysis of fish and EPADHA consumpti c2017 ae01864560 v123 aBACKGROUND: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences.
OBJECTIVE: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption.
DESIGN: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts.
RESULTS: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA.
CONCLUSIONS: These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.
10aAdult10aAged10aCohort Studies10aDocosahexaenoic Acids10aEicosapentaenoic Acid10aEurope10aEuropean Continental Ancestry Group10aFemale10aGenome-Wide Association Study10aHumans10aMale10aMiddle Aged10aSeafood10aUnited States1 aMozaffarian, Dariush1 aDashti, Hassan, S1 aWojczynski, Mary, K1 aChu, Audrey, Y1 aNettleton, Jennifer, A1 aMännistö, Satu1 aKristiansson, Kati1 aReedik, Mägi1 aLahti, Jari1 aHouston, Denise, K1 aCornelis, Marilyn, C1 avan Rooij, Frank, J A1 aDimitriou, Maria1 aKanoni, Stavroula1 aMikkilä, Vera1 aSteffen, Lyn, M1 aOtto, Marcia, C de Olive1 aQi, Lu1 aPsaty, Bruce1 aDjoussé, Luc1 aRotter, Jerome, I1 aHarald, Kennet1 aPerola, Markus1 aRissanen, Harri1 aJula, Antti1 aKrista, Fischer1 aMihailov, Evelin1 aFeitosa, Mary, F1 aNgwa, Julius, S1 aXue, Luting1 aJacques, Paul, F1 aPerälä, Mia-Maria1 aPalotie, Aarno1 aLiu, Yongmei1 aNalls, Nike, A1 aFerrucci, Luigi1 aHernandez, Dena1 aManichaikul, Ani1 aTsai, Michael, Y1 ade Jong, Jessica, C Kiefte-1 aHofman, Albert1 aUitterlinden, André, G1 aRallidis, Loukianos1 aRidker, Paul, M1 aRose, Lynda, M1 aBuring, Julie, E1 aLehtimäki, Terho1 aKähönen, Mika1 aViikari, Jorma1 aLemaitre, Rozenn1 aSalomaa, Veikko1 aKnekt, Paul1 aMetspalu, Andres1 aBorecki, Ingrid, B1 aCupples, Adrienne, L1 aEriksson, Johan, G1 aKritchevsky, Stephen, B1 aBandinelli, Stefania1 aSiscovick, David1 aFranco, Oscar, H1 aDeloukas, Panos1 aDedoussis, George1 aChasman, Daniel, I1 aRaitakari, Olli1 aTanaka, Toshiko uhttps://chs-nhlbi.org/node/7578