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FTO genotype is associated with phenotypic variability of body mass index

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 and Maegi, Reedik, et al. (2012) In Nature 490(7419). p.267-272
Abstract
There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), 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 similar to 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... (More)
There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), 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 similar to 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)(5-7), 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 similar to 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 BMI8, possibly mediated by DNA methylation(9,10). 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. (Less)
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Nature
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490
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7419
pages
267 - 272
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Nature Publishing Group
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  • wos:000309733300051
  • scopus:84867330691
ISSN
0028-0836
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10.1038/nature11401
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English
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264098a2-9518-4ab8-af3e-b374f7e2cb2c (old id 3244333)
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@article{264098a2-9518-4ab8-af3e-b374f7e2cb2c,
  abstract     = {There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), 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 similar to 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)(5-7), 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 similar to 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 BMI8, possibly mediated by DNA methylation(9,10). 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.},
  author       = {Yang, Jian and Loos, Ruth J. F. and Powell, Joseph E. and Medland, Sarah E. and Speliotes, Elizabeth K. and Chasman, Daniel I. and Rose, Lynda M. and Thorleifsson, Gudmar and Steinthorsdottir, Valgerdur and Maegi, Reedik and Waite, Lindsay and Smith, Albert Vernon and Yerges-Armstrong, Laura M. and Monda, Keri L. and Hadley, David and Mahajan, Anubha and Li, Guo and Kapur, Karen and Vitart, Veronique and Huffman, Jennifer E. and Wang, Sophie R. and Palmer, Cameron and Esko, Toenu and Fischer, Krista and Zhao, Jing Hua and Demirkan, Ayse and Isaacs, Aaron and Feitosa, Mary F. and Luan, Jian'an and Heard-Costa, Nancy L. and White, Charles and Jackson, Anne U. and Preuss, Michael and Ziegler, Andreas and Eriksson, Joel and Kutalik, Zoltan and Frau, Francesca and Nolte, Ilja M. and Van Vliet-Ostaptchouk, Jana V. and Hottenga, Jouke-Jan and Jacobs, Kevin B. and Verweij, Niek and Goel, Anuj and Medina-Gomez, Carolina and Estrada, Karol and Bragg-Gresham, Jennifer Lynn and Sanna, Serena and Sidore, Carlo and Tyrer, Jonathan and Teumer, Alexander and Prokopenko, Inga and Mangino, Massimo and Lindgren, Cecilia M. and Assimes, Themistocles L. and Shuldiner, Alan R. and Hui, Jennie and Beilby, John P. and McArdle, Wendy L. and Hall, Per and Haritunians, Talin and Zgaga, Lina and Kolcic, Ivana and Polasek, Ozren and Zemunik, Tatijana and Oostra, Ben A. and Junttila, M. Juhani and Groenberg, Henrik and Schreiber, Stefan and Peters, Annette and Hicks, Andrew A. and Stephens, Jonathan and Foad, Nicola S. and Laitinen, Jaana and Pouta, Anneli and Kaakinen, Marika and Willemsen, Gonneke and Vink, Jacqueline M. and Wild, Sarah H. and Navis, Gerjan and Asselbergs, Folkert W. and Homuth, Georg and John, Ulrich and Iribarren, Carlos and Harris, Tamara and Launer, Lenore and Gudnason, Vilmundur and O'Connell, Jeffrey R. and Boerwinkle, Eric and Cadby, Gemma and Palmer, Lyle J. and James, Alan L. and Musk, Arthur W. and Ingelsson, Erik and Psaty, Bruce M. and Beckmann, Jacques S. and Waeber, Gerard and Vollenweider, Peter and Hayward, Caroline and Wright, Alan F. and Rudan, Igor and Groop, Leif and Metspalu, Andres and Khaw, Kay Tee and van Duijn, Cornelia M. and Borecki, Ingrid B. and Province, Michael A. and Wareham, Nicholas J. and Tardif, Jean-Claude and Huikuri, Heikki V. and Cupples, L. Adrienne and Atwood, Larry D. and Fox, Caroline S. and Boehnke, Michael and Collins, Francis S. and Mohlke, Karen L. and Erdmann, Jeanette and Schunkert, Heribert and Hengstenberg, Christian and Stark, Klaus and Lorentzon, Mattias and Ohlsson, Claes and Cusi, Daniele and Staessen, Jan A. and Van der Klauw, Melanie M. and Pramstaller, Peter P. and Kathiresan, Sekar and Jolley, Jennifer D. and Ripatti, Samuli and Jarvelin, Marjo-Riitta and de Geus, Eco J. C. and Boomsma, Dorret I. and Penninx, Brenda and Wilson, James F. and Campbell, Harry and Chanock, Stephen J. and van der Harst, Pim and Hamsten, Anders and Watkins, Hugh and Hofman, Albert and Witteman, Jacqueline C. and Zillikens, M. Carola and Uitterlinden, Andre G. and Rivadeneira, Fernando and Zillikens, M. Carola and Kiemeney, Lambertus A. and Vermeulen, Sita H. and Abecasis, Goncalo R. and Schlessinger, David and Schipf, Sabine and Stumvoll, Michael and Toenjes, Anke and Spector, Tim D. and North, Kari E. and Lettre, Guillaume and McCarthy, Mark I. and Berndt, Sonja I. and Heath, Andrew C. and Madden, Pamela A. F. and Nyholt, Dale R. and Montgomery, Grant W. and Martin, Nicholas G. and McKnight, Barbara and Strachan, David P. and Hill, William G. and Snieder, Harold and Ridker, Paul M. and Thorsteinsdottir, Unnur and Stefansson, Kari and Frayling, Timothy M. and Hirschhorn, Joel N. and Goddard, Michael E. and Visscher, Peter M.},
  issn         = {0028-0836},
  language     = {eng},
  number       = {7419},
  pages        = {267--272},
  publisher    = {Nature Publishing Group},
  series       = {Nature},
  title        = {FTO genotype is associated with phenotypic variability of body mass index},
  url          = {http://dx.doi.org/10.1038/nature11401},
  volume       = {490},
  year         = {2012},
}