Abstract
Original language | English |
---|---|
Pages (from-to) | 267-273 |
Journal | NATURE |
Volume | 490 |
Issue number | 7419 |
DOIs | |
Publication status | Published - 11 Oct 2012 |
Externally published | Yes |
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In: NATURE, Vol. 490, No. 7419, 11.10.2012, p. 267-273.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - FTO genotype is associated with phenotypic variability of body mass index
AU - Yang, Jian
AU - Loos, Ruth J. F.
AU - Powell, Joseph E.
AU - Medland, Sarah E.
AU - Speliotes, Elizabeth K.
AU - Chasman, Daniel I.
AU - Rose, Lynda M.
AU - Thorleifsson, Gudmar
AU - Steinthorsdottir, Valgerdur
AU - Mägi, Reedik
AU - Waite, Lindsay
AU - Vernon Smith, Albert
AU - Yerges-Armstrong, Laura M.
AU - Monda, Keri L.
AU - Hadley, David
AU - Mahajan, Anubha
AU - Li, Guo
AU - Kapur, Karen
AU - Vitart, Veronique
AU - Huffman, Jennifer E.
AU - Wang, Sophie R.
AU - Palmer, Cameron
AU - Esko, T. nu
AU - Fischer, Krista
AU - Hua Zhao, Jing
AU - Demirkan, Ayśe
AU - Isaacs, Aaron
AU - Feitosa, Mary F.
AU - Luan, Jian'An
AU - Heard-Costa, Nancy L.
AU - White, Charles
AU - Jackson, Anne U.
AU - Preuss, Michael
AU - Ziegler, Andreas
AU - Eriksson, Joel
AU - Kutalik, Zoltán
AU - Frau, Francesca
AU - Nolte, Ilja M.
AU - van Vliet-Ostaptchouk, Jana V.
AU - Hottenga, Jouke-Jan
AU - Jacobs, Kevin B.
AU - Verweij, Niek
AU - Goel, Anuj
AU - Medina-Gomez, Carolina
AU - Estrada, Karol
AU - Bragg-Gresham, Jennifer Lynn
AU - Sanna, Serena
AU - Sidore, Carlo
AU - Tyrer, Jonathan
AU - Teumer, Alexander
AU - Prokopenko, Inga
AU - Mangino, Massimo
AU - Lindgren, Cecilia M.
AU - Assimes, Themistocles L.
AU - Shuldiner, Alan R.
AU - Hui, Jennie
AU - Beilby, John P.
AU - McArdle, Wendy L.
AU - Hall, Per
AU - Haritunians, Talin
AU - Zgaga, Lina
AU - Kolcic, Ivana
AU - Polasek, Ozren
AU - Zemunik, Tatijana
AU - Oostra, Ben A.
AU - Juhani Junttila, M.
AU - Grönberg, Henrik
AU - Schreiber, Stefan
AU - Peters, Annette
AU - Hicks, Andrew A.
AU - Stephens, Jonathan
AU - Foad, Nicola S.
AU - Laitinen, Jaana
AU - Pouta, Anneli
AU - Kaakinen, Marika
AU - Willemsen, Gonneke
AU - Vink, Jacqueline M.
AU - Wild, Sarah H.
AU - Navis, Gerjan
AU - Asselbergs, Folkert W.
AU - Homuth, Georg
AU - John, Ulrich
AU - Iribarren, Carlos
AU - Harris, Tamara
AU - Launer, Lenore
AU - Gudnason, Vilmundur
AU - O'Connell, Jeffrey R.
AU - Boerwinkle, Eric
AU - Cadby, Gemma
AU - Palmer, Lyle J.
AU - James, Alan L.
AU - Musk, Arthur W.
AU - Ingelsson, Erik
AU - Psaty, Bruce M.
AU - Beckmann, Jacques S.
AU - Waeber, Gerard
AU - Vollenweider, Peter
AU - Hayward, Caroline
AU - Wright, Alan F.
AU - Rudan, Igor
AU - Groop, Leif C.
AU - Metspalu, Andres
AU - Tee Khaw, Kay
AU - van Duijn, Cornelia M.
AU - Borecki, Ingrid B.
AU - Province, Michael A.
AU - Wareham, Nicholas J.
AU - Tardif, Jean-Claude
AU - Huikuri, Heikki V.
AU - Adrienne Cupples, L.
AU - Atwood, Larry D.
AU - Fox, Caroline S.
AU - Boehnke, Michael
AU - Collins, Francis S.
AU - Mohlke, Karen L.
AU - Erdmann, Jeanette
AU - Schunkert, Heribert
AU - Hengstenberg, Christian
AU - Stark, Klaus
AU - Lorentzon, Mattias
AU - Ohlsson, Claes
AU - Cusi, Daniele
AU - Staessen, Jan A.
AU - van der Klauw, Melanie M.
AU - Pramstaller, Peter P.
AU - Kathiresan, Sekar
AU - Jolley, Jennifer D.
AU - Ripatti, Samuli
AU - Jarvelin, Marjo-Riitta
AU - de Geus, Eco J. C.
AU - Boomsma, Dorret I.
AU - Penninx, Brenda
AU - Wilson, James F.
AU - Campbell, Harry
AU - Chanock, Stephen J.
AU - van der Harst, Pim
AU - Hamsten, Anders
AU - Watkins, Hugh
AU - Hofman, Albert
AU - Witteman, Jacqueline C.
AU - Carola Zillikens, M.
AU - Uitterlinden, André G.
AU - Rivadeneira, Fernando
AU - Carola Zillikens, M.
AU - Kiemeney, Lambertus A.
AU - Vermeulen, Sita H.
AU - Abecasis, Goncalo R.
AU - Schlessinger, David
AU - Schipf, Sabine
AU - Stumvoll, Michael
AU - Tönjes, Anke
AU - Spector, Tim D.
AU - North, Kari E.
AU - Lettre, Guillaume
AU - McCarthy, Mark I.
AU - Berndt, Sonja I.
AU - Heath, Andrew C.
AU - Madden, Pamela A. F.
AU - Nyholt, Dale R.
AU - Montgomery, Grant W.
AU - Martin, Nicholas G.
AU - McKnight, Barbara
AU - Strachan, David P.
AU - Hill, William G.
AU - Snieder, Harold
AU - Ridker, Paul M.
AU - Thorsteinsdottir, Unnur
AU - Stefansson, Kari
AU - Frayling, Timothy M.
AU - Hirschhorn, Joel N.
AU - Goddard, Michael E.
AU - Visscher, Peter M.
PY - 2012/10/11
Y1 - 2012/10/11
N2 - 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. © 2012 Macmillan Publishers Limited. All rights reserved.
AB - 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. © 2012 Macmillan Publishers Limited. All rights reserved.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84867330691&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/22982992
U2 - https://doi.org/10.1038/nature11401
DO - https://doi.org/10.1038/nature11401
M3 - Article
C2 - 22982992
SN - 0028-0836
VL - 490
SP - 267
EP - 273
JO - NATURE
JF - NATURE
IS - 7419
ER -