Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22982992
TITLE
FTO genotype is associated with phenotypic variability of body mass index.
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.
DATE PUBLISHED
2012 Oct 11
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/01/15
accepted 2012/07/06
aheadofprint 2012/09/16
entrez 2012/09/18 06:00
pubmed 2012/09/18 06:00
medline 2012/11/07 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Yang J Yang Jian J University of Queensland Diamantina Institute, The University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia.
Loos RJ Loos Ruth J F RJ
Powell JE Powell Joseph E JE
Medland SE Medland Sarah E SE
Speliotes EK Speliotes Elizabeth K EK
Chasman DI Chasman Daniel I DI
Rose LM Rose Lynda M LM
Thorleifsson G Thorleifsson Gudmar G
Steinthorsdottir V Steinthorsdottir Valgerdur V
Mägi R Mägi Reedik R
Waite L Waite Lindsay L
Smith AV Smith Albert Vernon AV
Yerges-Armstrong LM Yerges-Armstrong Laura M LM
Monda KL Monda Keri L KL
Hadley D Hadley David D
Mahajan A Mahajan Anubha A
Li G Li Guo G
Kapur K Kapur Karen K
Vitart V Vitart Veronique V
Huffman JE Huffman Jennifer E JE
Wang SR Wang Sophie R SR
Palmer C Palmer Cameron C
Esko T Esko Tõnu T
Fischer K Fischer Krista K
Zhao JH Zhao Jing Hua JH
Demirkan A Demirkan Ayşe A
Isaacs A Isaacs Aaron A
Feitosa MF Feitosa Mary F MF
Luan J Luan Jian'an J
Heard-Costa NL Heard-Costa Nancy L NL
White C White Charles C
Jackson AU Jackson Anne U AU
Preuss M Preuss Michael M
Ziegler A Ziegler Andreas A
Eriksson J Eriksson Joel J
Kutalik Z Kutalik Zoltán Z
Frau F Frau Francesca F
Nolte IM Nolte Ilja M IM
Van Vliet-Ostaptchouk JV Van Vliet-Ostaptchouk Jana V JV
Hottenga JJ Hottenga Jouke-Jan JJ
Jacobs KB Jacobs Kevin B KB
Verweij N Verweij Niek N
Goel A Goel Anuj A
Medina-Gomez C Medina-Gomez Carolina C
Estrada K Estrada Karol K
Bragg-Gresham JL Bragg-Gresham Jennifer Lynn JL
Sanna S Sanna Serena S
Sidore C Sidore Carlo C
Tyrer J Tyrer Jonathan J
Teumer A Teumer Alexander A
Prokopenko I Prokopenko Inga I
Mangino M Mangino Massimo M
Lindgren CM Lindgren Cecilia M CM
Assimes TL Assimes Themistocles L TL
Shuldiner AR Shuldiner Alan R AR
Hui J Hui Jennie J
Beilby JP Beilby John P JP
McArdle WL McArdle Wendy L WL
Hall P Hall Per P
Haritunians T Haritunians Talin T
Zgaga L Zgaga Lina L
Kolcic I Kolcic Ivana I
Polasek O Polasek Ozren O
Zemunik T Zemunik Tatijana T
Oostra BA Oostra Ben A BA
Junttila MJ Junttila M Juhani MJ
Grönberg H Grönberg Henrik H
Schreiber S Schreiber Stefan S
Peters A Peters Annette A
Hicks AA Hicks Andrew A AA
Stephens J Stephens Jonathan J
Foad NS Foad Nicola S NS
Laitinen J Laitinen Jaana J
Pouta A Pouta Anneli A
Kaakinen M Kaakinen Marika M
Willemsen G Willemsen Gonneke G
Vink JM Vink Jacqueline M JM
Wild SH Wild Sarah H SH
Navis G Navis Gerjan G
Asselbergs FW Asselbergs Folkert W FW
Homuth G Homuth Georg G
John U John Ulrich U
Iribarren C Iribarren Carlos C
Harris T Harris Tamara T
Launer L Launer Lenore L
Gudnason V Gudnason Vilmundur V
O'Connell JR O'Connell Jeffrey R JR
Boerwinkle E Boerwinkle Eric E
Cadby G Cadby Gemma G
Palmer LJ Palmer Lyle J LJ
James AL James Alan L AL
Musk AW Musk Arthur W AW
Ingelsson E Ingelsson Erik E
Psaty BM Psaty Bruce M BM
Beckmann JS Beckmann Jacques S JS
Waeber G Waeber Gerard G
Vollenweider P Vollenweider Peter P
Hayward C Hayward Caroline C
Wright AF Wright Alan F AF
Rudan I Rudan Igor I
Groop LC Groop Leif C LC
Metspalu A Metspalu Andres A
Khaw KT Khaw Kay Tee KT
van Duijn CM van Duijn Cornelia M CM
Borecki IB Borecki Ingrid B IB
Province MA Province Michael A MA
Wareham NJ Wareham Nicholas J NJ
Tardif JC Tardif Jean-Claude JC
Huikuri HV Huikuri Heikki V HV
Cupples LA Cupples L Adrienne LA
Atwood LD Atwood Larry D LD
Fox CS Fox Caroline S CS
Boehnke M Boehnke Michael M
Collins FS Collins Francis S FS
Mohlke KL Mohlke Karen L KL
Erdmann J Erdmann Jeanette J
Schunkert H Schunkert Heribert H
Hengstenberg C Hengstenberg Christian C
Stark K Stark Klaus K
Lorentzon M Lorentzon Mattias M
Ohlsson C Ohlsson Claes C
Cusi D Cusi Daniele D
Staessen JA Staessen Jan A JA
Van der Klauw MM Van der Klauw Melanie M MM
Pramstaller PP Pramstaller Peter P PP
Kathiresan S Kathiresan Sekar S
Jolley JD Jolley Jennifer D JD
Ripatti S Ripatti Samuli S
Jarvelin MR Jarvelin Marjo-Riitta MR
de Geus EJ de Geus Eco J C EJ
Boomsma DI Boomsma Dorret I DI
Penninx B Penninx Brenda B
Wilson JF Wilson James F JF
Campbell H Campbell Harry H
Chanock SJ Chanock Stephen J SJ
van der Harst P van der Harst Pim P
Hamsten A Hamsten Anders A
Watkins H Watkins Hugh H
Hofman A Hofman Albert A
Witteman JC Witteman Jacqueline C JC
Zillikens MC Zillikens M Carola MC
Uitterlinden AG Uitterlinden André G AG
Rivadeneira F Rivadeneira Fernando F
Zillikens MC Zillikens M Carola MC
Kiemeney LA Kiemeney Lambertus A LA
Vermeulen SH Vermeulen Sita H SH
Abecasis GR Abecasis Goncalo R GR
Schlessinger D Schlessinger David D
Schipf S Schipf Sabine S
Stumvoll M Stumvoll Michael M
Tönjes A Tönjes Anke A
Spector TD Spector Tim D TD
North KE North Kari E KE
Lettre G Lettre Guillaume G
McCarthy MI McCarthy Mark I MI
Berndt SI Berndt Sonja I SI
Heath AC Heath Andrew C AC
Madden PA Madden Pamela A F PA
Nyholt DR Nyholt Dale R DR
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
McKnight B McKnight Barbara B
Strachan DP Strachan David P DP
Hill WG Hill William G WG
Snieder H Snieder Harold H
Ridker PM Ridker Paul M PM
Thorsteinsdottir U Thorsteinsdottir Unnur U
Stefansson K Stefansson Kari K
Frayling TM Frayling Timothy M TM
Hirschhorn JN Hirschhorn Joel N JN
Goddard ME Goddard Michael E ME
Visscher PM Visscher Peter M PM
INVESTIGATORS
JOURNAL
VOLUME: 490
ISSUE: 7419
TITLE: Nature
ISOABBREVIATION: Nature
YEAR: 2012
MONTH: Oct
DAY: 11
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-4687
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nature
COUNTRY: England
ISSNLINKING: 0028-0836
NLMUNIQUEID: 0410462
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Clin Genet. 1983 Jul;24(1):1-14 6684513
Cites Genetics. 2004 Dec;168(4):2089-97 15611178
Cites Philos Trans R Soc Lond B Biol Sci. 2005 Jul 29;360(1459):1513-27 16108138
Cites Science. 2007 May 11;316(5826):889-94 17434869
Cites Bioinformatics. 2007 May 15;23(10):1294-6 17384015
Cites Nat Genet. 2007 Jun;39(6):724-6 17496892
Cites Nat Genet. 2007 Jul;39(7):906-13 17572673
Cites Nature. 2007 Oct 18;449(7164):851-61 17943122
Cites Diabetes. 2008 Jan;57(1):95-101 17942823
Cites PLoS Genet. 2008 Apr;4(4):e1000049 18404214
Cites PLoS Genet. 2007 Jul;3(7):e115 17658951
Cites Arch Intern Med. 2008 Sep 8;168(16):1791-7 18779467
Cites Genet Res (Camb). 2008 Oct;90(5):385-95 19061529
Cites Poult Sci. 2009 Jun;88(6):1156-61 19439624
Cites Am J Clin Nutr. 2009 Oct;90(4):1096-103 19710197
Cites PLoS Genet. 2010 Jun;6(6):e1000981 20585554
Cites Behav Genet. 2010 Sep;40(5):728-33 20428936
Cites Bioinformatics. 2010 Sep 1;26(17):2190-1 20616382
Cites Bioinformatics. 2010 Sep 15;26(18):2336-7 20634204
Cites Nature. 2010 Oct 14;467(7317):832-8 20881960
Cites Nat Genet. 2010 Nov;42(11):937-48 20935630
Cites BMC Genet. 2010;11:92 20942902
Cites Genet Epidemiol. 2010 Dec;34(8):816-34 21058334
Cites PLoS One. 2010;5(11):e14040 21124985
Cites Genet Res (Camb). 2010 Dec;92(5-6):381-95 21429270
Cites Genetics. 2011 Jun;188(2):435-47 21467569
Cites PLoS Genet. 2011 Sep;7(9):e1002295 21980300
Cites PLoS Med. 2011 Nov;8(11):e1001116 22069379
Cites Nat Chem Biol. 2011 Dec;7(12):885-7 22002720
Cites Hum Mol Genet. 2012 Jan 15;21(2):371-83 21994764
Cites PLoS One. 2012;7(1):e28764 22235250
Cites Genomics. 2012 Mar;99(3):132-7 22234326
Cites Genet Res (Camb). 2011 Apr;93(2):125-38 21392419
Cites Biometrics. 1999 Dec;55(4):997-1004 11315092
GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
14136 Cancer Research UK United Kingdom
AA014041 NIAAA NIH HHS United States
AA07535 NIAAA NIH HHS United States
AA10248 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
CZB/4/710 Chief Scientist Office United Kingdom
DA12854 NIDA NIH HHS United States
F32 AR059469 NIAMS NIH HHS United States
F32 DK079466 NIDDK NIH HHS United States
G0601261 Medical Research Council United Kingdom
G1000143 Medical Research Council United Kingdom
GM057091 NIGMS NIH HHS United States
HHSN268201100005C NHLBI NIH HHS United States
HHSN268201100006C NHLBI NIH HHS United States
HHSN268201100007C NHLBI NIH HHS United States
HHSN268201100008C NHLBI NIH HHS United States
HHSN268201100009C NHLBI NIH HHS United States
HHSN268201100010C NHLBI NIH HHS United States
HHSN268201100011C NHLBI NIH HHS United States
HHSN268201100012C NHLBI NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
K23 DK080145 NIDDK NIH HHS United States
MC_PC_U127561128 Medical Research Council United Kingdom
MC_U106179471 Medical Research Council United Kingdom
MC_U127561128 Medical Research Council United Kingdom
N01 AG012100 NIA NIH HHS United States
N01 HC015103 NHLBI NIH HHS United States
N01 HC025195 NHLBI NIH HHS United States
N01 HC035129 NHLBI NIH HHS United States
N01 HC045133 NHLBI NIH HHS United States
N01 HC055222 NHLBI NIH HHS United States
N01 HC075150 NHLBI NIH HHS United States
N01 HC085079 NHLBI NIH HHS United States
N01 HG065403 NHGRI NIH HHS United States
N01HC85086 NHLBI NIH HHS United States
N02 HL64278 NHLBI NIH HHS United States
P30 DK063491 NIDDK NIH HHS United States
P30 DK072488 NIDDK NIH HHS United States
R01 AA007535 NIAAA NIH HHS United States
R01 AA013320 NIAAA NIH HHS United States
R01 AA013321 NIAAA NIH HHS United States
R01 AA013326 NIAAA NIH HHS United States
R01 AA014041 NIAAA NIH HHS United States
R01 AG015928 NIA NIH HHS United States
R01 AG020098 NIA NIH HHS United States
R01 AG023629 NIA NIH HHS United States
R01 AG027058 NIA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 DK062370 NIDDK NIH HHS United States
R01 DK072193 NIDDK NIH HHS United States
R01 DK073490 NIDDK NIH HHS United States
R01 DK075681 NIDDK NIH HHS United States
R01 DK075787 NIDDK NIH HHS United States
R01 HG002651 NHGRI NIH HHS United States
R01 HL043851 NHLBI NIH HHS United States
R01 HL059367 NHLBI NIH HHS United States
R01 HL075366 NHLBI NIH HHS United States
R01 HL080295 NHLBI NIH HHS United States
R01 HL086694 NHLBI NIH HHS United States
R01 HL087641 NHLBI NIH HHS United States
R01 HL087647 NHLBI NIH HHS United States
R01 HL087652 NHLBI NIH HHS United States
R01 HL087676 NHLBI NIH HHS United States
R01 HL087679 NHLBI NIH HHS United States
R01 HL105756 NHLBI NIH HHS United States
R01 LM010098 NLM NIH HHS United States
R01 MH063706 NIMH NIH HHS United States
RL1 MH083268 NIMH NIH HHS United States
U01 DK062418 NIDDK NIH HHS United States
U01 HG004402 NHGRI NIH HHS United States
U01 HL054527 NHLBI NIH HHS United States
U01 HL069757 NHLBI NIH HHS United States
U01 HL072515 NHLBI NIH HHS United States
U01 HL084729 NHLBI NIH HHS United States
U01 HL084756 NHLBI NIH HHS United States
U54 RR020278 NCRR NIH HHS United States
UL1 RR033176 NCRR NIH HHS United States
Z01 HG000024-14 Intramural NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Body Height genetics
Body Mass Index genetics
Co-Repressor Proteins genetics
Female genetics
Genetic Variation genetics
Genome-Wide Association Study genetics
Humans genetics
Male genetics
Nerve Tissue Proteins genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Proteins genetics
Repressor Proteins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Co-Repressor Proteins
0 FTO protein, human
0 Nerve Tissue Proteins
0 Proteins
0 RCOR1 protein, human
0 Repressor Proteins
OTHER ID's
OTHERID SOURCE
NIHMS433930 NLM
PMC3564953 NLM