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Title: FTO genotype is associated with phenotypic variability of body mass index
Authors: 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
Mägi, Reedik
Waite, Lindsay
Metspalu, Andres
Tee Khaw, Kay
van Duijn, Cornelia M
Borecki, Ingrid B
Province, Michael A
Wareham, Nicholas J
Tardif, Jean-Claude
Huikuri, Heikki V
Adrienne Cupples, L
Atwood, Larry D
Vernon Smith, Albert
Fox, Caroline S
Boehnke, Michael
Collins, Francis S
Mohlke, Karen L
Erdmann, Jeanette
Schunkert, Heribert
Hengstenberg, Christian
Stark, Klaus
Lorentzon, Mattias
Ohlsson, Claes
Yerges-Armstrong, Laura M
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
Monda, Keri L
Penninx, Brenda
Wilson, James F
Campbell, Harry
Chanock, Stephen J
van der Harst, Pim
Hamsten, Anders
Watkins, Hugh
Hofman, Albert
Witteman, Jacqueline C
Carola Zillikens, M
Hadley, David
Uitterlinden, André G
Rivadeneira, Fernando
Carola Zillikens, M
Kiemeney, Lambertus A
Vermeulen, Sita H
Abecasis, Goncalo R
Schlessinger, David
Schipf, Sabine
Stumvoll, Michael
Tönjes, Anke
Mahajan, Anubha
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
Kapur, Karen
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
Vitart, Veronique
Visscher, Peter M ×
Huffman, Jennifer E
Wang, Sophie R
Palmer, Cameron
Esko, Tõnu
Fischer, Krista
Hua Zhao, Jing
Demirkan, Ayşe
Isaacs, Aaron
Feitosa, Mary F
Luan, Jian'an
Heard-Costa, Nancy L
White, Charles
Jackson, Anne U
Preuss, Michael
Ziegler, Andreas
Eriksson, Joel
Kutalik, Zoltán
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
Lynn Bragg-Gresham, Jennifer
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
Juhani Junttila, M
Grönberg, 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 #
Issue Date: Oct-2012
Publisher: Nature Publishing Group
Series Title: Nature vol:490 issue:7419 pages:267-272
Article number: 10.1038/nature11401
Abstract: 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.
ISSN: 0028-0836
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hypertension and Cardiovascular Epidemiology
× corresponding author
# (joint) last author

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