TY - JOUR
T1 - FTO genotype is associated with phenotypic variability of body mass index.
JF - Nature
Y1 - 2012
A1 - Yang, Jian
A1 - Loos, Ruth J F
A1 - Powell, Joseph E
A1 - Medland, Sarah E
A1 - Speliotes, Elizabeth K
A1 - Chasman, Daniel I
A1 - Rose, Lynda M
A1 - Thorleifsson, Gudmar
A1 - Steinthorsdottir, Valgerdur
A1 - Mägi, Reedik
A1 - Waite, Lindsay
A1 - Smith, Albert Vernon
A1 - Yerges-Armstrong, Laura M
A1 - Monda, Keri L
A1 - Hadley, David
A1 - Mahajan, Anubha
A1 - Li, Guo
A1 - Kapur, Karen
A1 - Vitart, Veronique
A1 - Huffman, Jennifer E
A1 - Wang, Sophie R
A1 - Palmer, Cameron
A1 - Esko, Tõnu
A1 - Fischer, Krista
A1 - Zhao, Jing Hua
A1 - Demirkan, Ayse
A1 - Isaacs, Aaron
A1 - Feitosa, Mary F
A1 - Luan, Jian'an
A1 - Heard-Costa, Nancy L
A1 - White, Charles
A1 - Jackson, Anne U
A1 - Preuss, Michael
A1 - Ziegler, Andreas
A1 - Eriksson, Joel
A1 - Kutalik, Zoltán
A1 - Frau, Francesca
A1 - Nolte, Ilja M
A1 - van Vliet-Ostaptchouk, Jana V
A1 - Hottenga, Jouke-Jan
A1 - Jacobs, Kevin B
A1 - Verweij, Niek
A1 - Goel, Anuj
A1 - Medina-Gómez, Carolina
A1 - Estrada, Karol
A1 - Bragg-Gresham, Jennifer Lynn
A1 - Sanna, Serena
A1 - Sidore, Carlo
A1 - Tyrer, Jonathan
A1 - Teumer, Alexander
A1 - Prokopenko, Inga
A1 - Mangino, Massimo
A1 - Lindgren, Cecilia M
A1 - Assimes, Themistocles L
A1 - Shuldiner, Alan R
A1 - Hui, Jennie
A1 - Beilby, John P
A1 - McArdle, Wendy L
A1 - Hall, Per
A1 - Haritunians, Talin
A1 - Zgaga, Lina
A1 - Kolcic, Ivana
A1 - Polasek, Ozren
A1 - Zemunik, Tatijana
A1 - Oostra, Ben A
A1 - Junttila, M Juhani
A1 - Grönberg, Henrik
A1 - Schreiber, Stefan
A1 - Peters, Annette
A1 - Hicks, Andrew A
A1 - Stephens, Jonathan
A1 - Foad, Nicola S
A1 - Laitinen, Jaana
A1 - Pouta, Anneli
A1 - Kaakinen, Marika
A1 - Willemsen, Gonneke
A1 - Vink, Jacqueline M
A1 - Wild, Sarah H
A1 - Navis, Gerjan
A1 - Asselbergs, Folkert W
A1 - Homuth, Georg
A1 - John, Ulrich
A1 - Iribarren, Carlos
A1 - Harris, Tamara
A1 - Launer, Lenore
A1 - Gudnason, Vilmundur
A1 - O'Connell, Jeffrey R
A1 - Boerwinkle, Eric
A1 - Cadby, Gemma
A1 - Palmer, Lyle J
A1 - James, Alan L
A1 - Musk, Arthur W
A1 - Ingelsson, Erik
A1 - Psaty, Bruce M
A1 - Beckmann, Jacques S
A1 - Waeber, Gérard
A1 - Vollenweider, Peter
A1 - Hayward, Caroline
A1 - Wright, Alan F
A1 - Rudan, Igor
A1 - Groop, Leif C
A1 - Metspalu, Andres
A1 - Khaw, Kay Tee
A1 - van Duijn, Cornelia M
A1 - Borecki, Ingrid B
A1 - Province, Michael A
A1 - Wareham, Nicholas J
A1 - Tardif, Jean-Claude
A1 - Huikuri, Heikki V
A1 - Cupples, L Adrienne
A1 - Atwood, Larry D
A1 - Fox, Caroline S
A1 - Boehnke, Michael
A1 - Collins, Francis S
A1 - Mohlke, Karen L
A1 - Erdmann, Jeanette
A1 - Schunkert, Heribert
A1 - Hengstenberg, Christian
A1 - Stark, Klaus
A1 - Lorentzon, Mattias
A1 - Ohlsson, Claes
A1 - Cusi, Daniele
A1 - Staessen, Jan A
A1 - van der Klauw, Melanie M
A1 - Pramstaller, Peter P
A1 - Kathiresan, Sekar
A1 - Jolley, Jennifer D
A1 - Ripatti, Samuli
A1 - Jarvelin, Marjo-Riitta
A1 - de Geus, Eco J C
A1 - Boomsma, Dorret I
A1 - Penninx, Brenda
A1 - Wilson, James F
A1 - Campbell, Harry
A1 - Chanock, Stephen J
A1 - van der Harst, Pim
A1 - Hamsten, Anders
A1 - Watkins, Hugh
A1 - Hofman, Albert
A1 - Witteman, Jacqueline C
A1 - Zillikens, M Carola
A1 - Uitterlinden, André G
A1 - Rivadeneira, Fernando
A1 - Zillikens, M Carola
A1 - Kiemeney, Lambertus A
A1 - Vermeulen, Sita H
A1 - Abecasis, Goncalo R
A1 - Schlessinger, David
A1 - Schipf, Sabine
A1 - Stumvoll, Michael
A1 - Tönjes, Anke
A1 - Spector, Tim D
A1 - North, Kari E
A1 - Lettre, Guillaume
A1 - McCarthy, Mark I
A1 - Berndt, Sonja I
A1 - Heath, Andrew C
A1 - Madden, Pamela A F
A1 - Nyholt, Dale R
A1 - Montgomery, Grant W
A1 - Martin, Nicholas G
A1 - McKnight, Barbara
A1 - Strachan, David P
A1 - Hill, William G
A1 - Snieder, Harold
A1 - Ridker, Paul M
A1 - Thorsteinsdottir, Unnur
A1 - Stefansson, Kari
A1 - Frayling, Timothy M
A1 - Hirschhorn, Joel N
A1 - Goddard, Michael E
A1 - Visscher, Peter M
KW - Alpha-Ketoglutarate-Dependent Dioxygenase FTO
KW - Body Height
KW - Body Mass Index
KW - Co-Repressor Proteins
KW - Female
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Nerve Tissue Proteins
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Proteins
KW - Repressor Proteins
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.

VL - 490
IS - 7419
U1 - http://www.ncbi.nlm.nih.gov/pubmed/22982992?dopt=Abstract
ER -