FTO genotype is associated with phenotypic variability of body mass index.
FTO genotype is associated with phenotypic variability of body mass index.
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DOI：
10.1038/nature11401
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发表时间：
2012-10-11
期刊：
影响因子：
64.8
通讯作者：
Visscher, Peter M.
中科院分区：
文献类型：
--
作者：
Yang, Jian;Loos, Ruth J. F.;Powell, Joseph E.;Medland, Sarah E.;Speliotes, Elizabeth K.;Chasman, Daniel I.;Rose, Lynda M.;Thorleifsson, Gudmar;Steinthorsdottir, Valgerdur;Maegi, Reedik;Waite, Lindsay;Smith, Albert Vernon;Yerges-Armstrong, Laura M.;Monda, Keri L.;Hadley, David;Mahajan, Anubha;Li, Guo;Kapur, Karen;Vitart, Veronique;Huffman, Jennifer E.;Wang, Sophie R.;Palmer, Cameron;Esko, Toenu;Fischer, Krista;Zhao, Jing Hua;Demirkan, Ayse;Isaacs, Aaron;Feitosa, Mary F.;Luan, Jian'an;Heard-Costa, Nancy L.;White, Charles;Jackson, Anne U.;Preuss, Michael;Ziegler, Andreas;Eriksson, Joel;Kutalik, Zoltan;Frau, Francesca;Nolte, Ilja M.;Van Vliet-Ostaptchouk, Jana V.;Hottenga, Jouke-Jan;Jacobs, Kevin B.;Verweij, Niek;Goel, Anuj;Medina-Gomez, Carolina;Estrada, Karol;Bragg-Gresham, Jennifer Lynn;Sanna, Serena;Sidore, Carlo;Tyrer, Jonathan;Teumer, Alexander;Prokopenko, Inga;Mangino, Massimo;Lindgren, Cecilia M.;Assimes, Themistocles L.;Shuldiner, Alan R.;Hui, Jennie;Beilby, John P.;McArdle, Wendy L.;Hall, Per;Haritunians, Talin;Zgaga, Lina;Kolcic, Ivana;Polasek, Ozren;Zemunik, Tatijana;Oostra, Ben A.;Junttila, M. Juhani;Groenberg, Henrik;Schreiber, Stefan;Peters, Annette;Hicks, Andrew A.;Stephens, Jonathan;Foad, Nicola S.;Laitinen, Jaana;Pouta, Anneli;Kaakinen, Marika;Willemsen, Gonneke;Vink, Jacqueline M.;Wild, Sarah H.;Navis, Gerjan;Asselbergs, Folkert W.;Homuth, Georg;John, Ulrich;Iribarren, Carlos;Harris, Tamara;Launer, Lenore;Gudnason, Vilmundur;O'Connell, Jeffrey R.;Boerwinkle, Eric;Cadby, Gemma;Palmer, Lyle J.;James, Alan L.;Musk, Arthur W.;Ingelsson, Erik;Psaty, Bruce M.;Beckmann, Jacques S.;Waeber, Gerard;Vollenweider, Peter;Hayward, Caroline;Wright, Alan F.;Rudan, Igor;Groop, Leif C.;Metspalu, Andres;Khaw, Kay Tee;van Duijn, Cornelia M.;Borecki, Ingrid B.;Province, Michael A.;Wareham, Nicholas J.;Tardif, Jean-Claude;Huikuri, Heikki V.;Cupples, L. Adrienne;Atwood, Larry D.;Fox, Caroline S.;Boehnke, Michael;Collins, Francis S.;Mohlke, Karen L.;Erdmann, Jeanette;Schunkert, Heribert;Hengstenberg, Christian;Stark, Klaus;Lorentzon, Mattias;Ohlsson, Claes;Cusi, Daniele;Staessen, Jan A.;Van der Klauw, Melanie M.;Pramstaller, Peter P.;Kathiresan, Sekar;Jolley, Jennifer D.;Ripatti, Samuli;Jarvelin, Marjo-Riitta;de Geus, Eco J. C.;Boomsma, Dorret I.;Penninx, Brenda;Wilson, James F.;Campbell, Harry;Chanock, Stephen J.;van der Harst, Pim;Hamsten, Anders;Watkins, Hugh;Hofman, Albert;Witteman, Jacqueline C.;Zillikens, M. Carola;Uitterlinden, Andre G.;Rivadeneira, Fernando;Zillikens, M. Carola;Kiemeney, Lambertus A.;Vermeulen, Sita H.;Abecasis, Goncalo R.;Schlessinger, David;Schipf, Sabine;Stumvoll, Michael;Toenjes, Anke;Spector, Tim D.;North, Kari E.;Lettre, Guillaume;McCarthy, Mark I.;Berndt, Sonja I.;Heath, Andrew C.;Madden, Pamela A. F.;Nyholt, Dale R.;Montgomery, Grant W.;Martin, Nicholas G.;McKnight, Barbara;Strachan, David P.;Hill, William G.;Snieder, Harold;Ridker, Paul M.;Thorsteinsdottir, Unnur;Stefansson, Kari;Frayling, Timothy M.;Hirschhorn, Joel N.;Goddard, Michael E.;Visscher, Peter M.
有证据表明，在几个物种中，复杂性状的表型变异受到遗传控制，因此表型之间的变异是基因型依赖的。了解变异性的遗传控制在进化生物学、农业选择方案和人类医学中很重要，但对于复杂性状，没有发现与方差相关的个体遗传变异，而不是平均值。在这里，我们使用170，000个人类人群身高和体重指数（BMI）样本对表型变异的全基因组关联研究进行荟萃分析。我们报告的证据表明，FTO基因位点的单核苷酸多态性（SNP）rs7202116，这是已知的与肥胖（测量每个rs7202116基因型的平均BMI），也与表型变异。我们表明，结果是不是由于规模效应或其他文物，并没有发现其他实验方面的显着证据的影响变异性，无论是在基因座以外的FTO的BMI或在任何位点的高度。在FTO基因座上具有相反纯合基因型的个体之间BMI的方差差异约为7%，对应于体重标准差的0.5千克差异。我们的研究结果表明，可以发现与变异性相关的遗传变异，肥胖症的人与人之间的变异性可以部分地由FTO基因座的基因型解释。结果与报告的FTO与BMI的环境相互作用一致，可能由DNA甲基化介导。我们对其他SNP的BMI结果和所有SNP的身高结果表明，大多数遗传变异，包括那些影响平均身高或平均BMI的变异，与表型方差无关，或者它们对变异性的影响太小，即使样本量超过100，000也无法检测到。
There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
2.9
作者：
Struchalin MV;Dehghan A;Witteman JC;van Duijn C;Aulchenko YS
通讯作者：
Aulchenko YS
影响因子：
4.4
作者：
Almen, Markus Sallman;Jacobsson, Josefin A.;Schioth, Helgi B.
通讯作者：
Schioth, Helgi B.