Biological Sciences Division
Published June 6, 2013 | Version v1
Journal article Open

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

Creators

  • 1. University of Oxford
  • 2. University of Regensburg
  • 3. University of Lausanne
  • 4. National Cancer Institute
  • 5. University of Michigan
  • 6. University of North Carolina at Chapel Hill
  • 7. Addenbrooke's Hospital
  • 8. University of Tartu
  • 9. Harvard University
  • 10. Washington University in St. Louis
  • 11. Karolinska Institutet
  • 12. University of Chicago

Description

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10−8), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

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Additional details

Identifiers

DOI
10.1371/journal.pgen.1003500
Other
oai:uchicago.tind.io:9551

Funding

Aarne Koskelon Säätiö
Research Council of Finland
40758
Research Council of Finland
41071
Research Council of Finland
77299
Research Council of Finland
102318
Research Council of Finland
104781
Research Council of Finland
110413
Research Council of Finland
117787
Research Council of Finland
117844
Research Council of Finland
118065
Research Council of Finland
118590
Research Council of Finland
120315
Research Council of Finland
120386
Research Council of Finland
121584
Research Council of Finland
123885
Research Council of Finland
124243
Research Council of Finland
124282
Research Council of Finland
125876
Research Council of Finland
126925
Research Council of Finland
129269
Research Council of Finland
129293
Research Council of Finland
129322
Research Council of Finland
129378
Research Council of Finland
129494
Research Council of Finland
129680
Research Council of Finland
139635
Research Council of Finland
211497
Research Council of Finland
213506
Research Council of Finland
250207
Research Council of Finland
1114194
ALF, Swedish government
research grant
Agency for Science, Technology and Research
Althingi
American Heart Association
0730094N
Australian Research Council
DP0770096
Australian Research Council
DP1093900
Biocentrum Helsinki
Boston Medical Center
Boston University
British Diabetes Association
British Heart Foundation
PG/02/128
British Heart Foundation
PG/07/133/24260
British Heart Foundation
RG2008/08
British Heart Foundation
RG2008/014
Cancer Research UK
C490/A8339
Cancer Research UK
C490/A10124
Central Norway Regional Health Authority
University Hospital of Lausanne
Chief Scientist Office
City of Kuopio
Deutsche Forschungsgemeinschaft
German Center for Diabetes Research
Diabetes UK
Donald W. Reynolds Foundation
Technische Universität Dresden
Funding Grant
Hersenstichting
Dutch Diabetes Research Foundation
Nierstichting
E033
Netherlands Heart Institute
Amsterdam Public Health
Emil Aaltosen Säätiö
Erasmus MC
Erasmus University Rotterdam
Estonian Government
SF0180142s08
Estonian Biocentre Centre of Excellence in Genomics
European Commission
FP5-QLG2-CT-2002-00896
European Commission
FP5-QLG2-CT-2002-01254
European Commission
FP5-QLRT-2001-01254
European Commission
FP6-LSHM-CT-2004-005272
European Commission
FP6-LSHM-CT-2004-503485
European Commission
FP6-LSHG-CT-2004-518153
European Commission
FP6-LSHG-CT-2006-018947
European Commission
FP6-LSHM-CT-2006-037593
European Commission
FP6-LSHM-CT-2006-037697
European Commission
FP6-LSHM-CT-2007-037273
European Commission
FP7-HEALTH-201413
European Commission
FP7-HEALTH-201536
European Commission
FP7-HEALTH-201550
European Commission
FP7-HEALTH-201668
European Commission
FP7-HEALTH-201865
European Commission
FP7-HEALTH-230374
European Commission
FP7-HEALTH-245536
European Commission
FP7-HEALTH-261433
Directorate of Health
2004310
Unknown funder
Marie Curie Intra-European Fellowship
European Union
EURO-BLCS, Framework 5 award
European Union
European Regional Development Fund
European Science Foundation
Federal State of Mecklenburg-West Pomerania
Finnish Cultural Foundation
Diabetes Tutkimussaatio
Finnish Foundation for Cardiovascular Research
Tekes
40058/07
Tekes
70103/06
Finnish Heart Association
Finnish Medical Society Duodecim
Ministry of Education and Culture
627:2004–2011
Ministry of Social Affairs and Health
5254
Finnish Institute for Health and Welfare
Finnish Slot Machine Association
Folkhälsanin Tutkimussäätiö
Fondation Leducq
Finnish Institute for Health and Welfare
Foundation for the National Institutes of Health
Genetic Association Information Network
Deutsches Diabetes-Zentrum e.V.
Bundesministerium für Forschung, Technologie und Raumfahrt
01KU0908A
Bundesministerium für Forschung, Technologie und Raumfahrt
01AK803A-H
Bundesministerium für Forschung, Technologie und Raumfahrt
01IG07015G
Bundesministerium für Forschung, Technologie und Raumfahrt
01GS0823
Bundesministerium für Forschung, Technologie und Raumfahrt
01GS0834
Bundesministerium für Forschung, Technologie und Raumfahrt
01ZZ0103
Bundesministerium für Forschung, Technologie und Raumfahrt
01ZZ0403
Bundesministerium für Forschung, Technologie und Raumfahrt
01ZZ9603
Bundesministerium für Forschung, Technologie und Raumfahrt
03ZIK012
Bundesministerium für Forschung, Technologie und Raumfahrt
01ER1206
Helmholtz Zentrum München
GlaxoSmithKline (United States)
Göteborg Medical Society
Unknown funder
The Great Wine Estates of the Margaret River region of Western Australia
Greek General Secretary of Research and Technology
Healthway, Western Australia
Heinz Nixdorf Foundation
Helmholtz Zentrum München
Helsinki University Central Hospital
Hjartavernd
Hospital district of Pirkanmaa, South Ostrobothnia, and Central Finland
International Stichting Alzheimer Onderzoek
Italian Ministry of Health
John D. and Catherine T. MacArthur Foundation
Juho Vainio Foundation
Juvenile Diabetes Research Foundation International
Karolinska Institutet
Stockholm County Council
560183
Stockholm County Council
562183
Knut and Alice Wallenberg Foundation
Lundberg Foundation
March of Dimes
6-FY-09-507
Medical Research Foundation of Umeå University
Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano
Ministry of Science, Education and Sports of the Republic of Croatia
108-1080315-0302
Montreal Heart Institute Foundation
The Municipal Health Care Center and Hospital in Jakobstad
Municipality of Nijmegen
Municipality of Rotterdam
Närpes Health Care Foundation
National Alliance for Research on Schizophrenia and Depression
National Health and Medical Research Council of Australia
241944
National Health and Medical Research Council of Australia
389875
National Health and Medical Research Council of Australia
389891
National Health and Medical Research Council of Australia
389892
National Health and Medical Research Council of Australia
389938
National Health and Medical Research Council of Australia
442915
National Health and Medical Research Council of Australia
442981
National Health and Medical Research Council of Australia
496739
National Health and Medical Research Council of Australia
496688
National Health and Medical Research Council of Australia
552485
National Health and Medical Research Council of Australia
613672
National Health and Medical Research Council of Australia
613601
National Health and Medical Research Council of Australia
1011506
Netherlands Brain Foundation
Netherlands Centre for Medical Systems Biology
Netherlands Ministry of Health, Welfare and Sport
Netherlands Organization for Scientific Research
014-93-015
Netherlands Organization for Scientific Research
050-060-810
Netherlands Organization for Scientific Research
40-0056-98-9032
Netherlands Organization for Scientific Research
175-010-2005-011
Netherlands Organization for Scientific Research
175-010-2007-006
Netherlands Organization for Scientific Research
184-021-007
Netherlands Organization for Scientific Research
311-60-008
Netherlands Organization for Scientific Research
400-05-717
Netherlands Organization for Scientific Research
480-04-004
Netherlands Organization for Scientific Research
480-05-003
Netherlands Organization for Scientific Research
904-61-090
Netherlands Organization for Scientific Research
904-61-193
Netherlands Organization for Scientific Research
911-03-012
Netherlands Organization for Scientific Research
916-761-70
Netherlands Organization for Scientific Research
985-10-002
Netherlands Organization for Scientific Research
SPI 56-464-14192
Neuroscience Campus Amsterdam
NHS
Support for Science Funding Programme
Nord-Trøndelag County Council
Nordic Center of Cardiovascular Research
Nordic Centre of Excellence in Disease Genetics, Nordic Centre of Excellence in Systems Biology
070014
Northern Netherlands Collaboration of Provinces
Norwegian Institute of Public Health
Norwegian Research Council
185764
Norwegian University of Science and Technology
Novo Nordisk Foundation
Ollqvist Foundation
Orion-Farmos Research Foundation
Paavo Nurmi Foundation
Päivikki and Sakari Sohlberg Foundation
Paul Michael Donovan Charitable Foundation
Perklén Foundation
Petrus and Augusta Hedlunds Foundation
Province of Groningen
Radboud University Nijmegen Medical Centre
Royal Swedish Academy of Science
Sardstedt AG & Co.
Siemens Healthcare
Signe and Ane Gyllenberg Foundation
Sigrid Juselius Foundation
Social Insurance Institution of Finland
4/26/2010
South Tyrolean Sparkasse Foundation
Susan G. Komen Breast Cancer Foundation
Swedish Cancer Society, Swedish Cultural Foundation in Finland
Swedish Diabetes Association
Swedish Foundation for Strategic Research
Swedish Heart-Lung Foundation
Swedish Research Council
0593
Swedish Research Council
8691
Swedish Research Council
2006-3832
Swedish Research Council
K2007-66X-20270-01-3
Swedish Research Council
K2010-54X-09894-19-3
Swiss National Science Foundation
310000-112552
Swiss National Science Foundation
33CSCO-122661
Tampere Tuberculosis Foundation
Torsten and Ragnar Söderberg Foundation
UK Economic and Social Research Council
UK Medical Research Council
Centre for Obesity and Related Metabolic Disease, Centre of Epidemiology for Child Health, PrevMetSyn/SALVE, MRC-GSK pilot programme
UK Medical Research Council
Centre for Obesity and Related Metabolic Disease, Centre of Epidemiology for Child Health, PrevMetSyn/SALVE, MRC-GSK pilot programme
UK Medical Research Council
Centre for Obesity and Related Metabolic Disease, Centre of Epidemiology for Child Health, PrevMetSyn/SALVE, MRC-GSK pilot programme
UK Medical Research Council
Centre for Obesity and Related Metabolic Disease, Centre of Epidemiology for Child Health, PrevMetSyn/SALVE, MRC-GSK pilot programme
UK Medical Research Council
Centre for Obesity and Related Metabolic Disease, Centre of Epidemiology for Child Health, PrevMetSyn/SALVE, MRC-GSK pilot programme
UK Medical Research Council
Centre for Obesity and Related Metabolic Disease, Centre of Epidemiology for Child Health, PrevMetSyn/SALVE, MRC-GSK pilot programme
UK National Institute for Health Research
RP-PG-0310-1002
University Hospital Essen
University Hospital Kuopio
University Hospital Oulu
University Hospital Tampere
University Hospital Turku
University of Groningen
University of Lausanne
University of Leipzig
University of Tromsø
University Medical Center Groningen
University of Tartu
US Department of Agriculture
National Research Initiative Competitive Grant
US National Cancer Institute
US National Heart, Lung, and Blood Institute
268200625226C
US National Heart, Lung, and Blood Institute
268201100005C
US National Heart, Lung, and Blood Institute
268201100006C
US National Heart, Lung, and Blood Institute
268201100007C
US National Heart, Lung, and Blood Institute
268201100008C
US National Heart, Lung, and Blood Institute
268201100009C
US National Heart, Lung, and Blood Institute
268201100010C
US National Heart, Lung, and Blood Institute
268201100011C
US National Heart, Lung, and Blood Institute
268201100012C
US National Heart, Lung, and Blood Institute
5R01HL087679-02
US National Heart, Lung, and Blood Institute
1RL1MH083268-01
US National Human Genome Research Institute
US National Institute of Allergy and Infectious Diseases
5R01MH63706:02
US National Institute of Allergy and Infectious Diseases
R01AA007535
US National Institute of Allergy and Infectious Diseases
R01AA014041
US National Institute of Allergy and Infectious Diseases
R01AA013320
US National Institute of Allergy and Infectious Diseases
R01AA013321
US National Institute of Allergy and Infectious Diseases
R01AA013326
US National Institute of Allergy and Infectious Diseases
R01AG004563
Eunice Kennedy Shriver National Institute of Child Health and Human Development
K23DK080145
Eunice Kennedy Shriver National Institute of Child Health and Human Development
P01CA87969
National Institute of Diabetes and Digestive and Kidney Diseases
P30DK063491
National Institute of Diabetes and Digestive and Kidney Diseases
P30DK072488
National Institutes of Health
M01RR16500
National Institutes of Health
N01AG12100
National Institutes of Health
N01AG12109
National Institutes of Health
N01HC25195
National Institutes of Health
N01HC35129
National Institutes of Health
N01HC85079
National Institutes of Health
N01HC85080
National Institutes of Health
N01HC85081
National Institutes of Health
N01HC85082
National Institutes of Health
N01HC85083
National Institutes of Health
N01HC85084
National Institutes of Health
N01HC85085
National Institutes of Health
N01HC85086
National Institutes of Health
N01HC85239
National Institutes of Health
N01HG65403
National Institutes of Health
N02HL64278
Swedish Research Council
K2010-52X-20229-05-3

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Medicine