Advanced

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

Randall, Joshua C.; Winkler, Thomas W.; Kutalik, Zoltan; Berndt, Sonja I.; Jackson, Anne U.; Monda, Keri L.; Kilpelaeinen, Tuomas O.; Esko, Tonu; Maegi, Reedik and Li, Shengxu, et al. (2013) In PLoS Genetics 9(6).
Abstract
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<5x10(-8)), but not in men. Sex-differences were... (More)
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<5x10(-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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Genetics
volume
9
issue
6
publisher
Public Library of Science
external identifiers
  • wos:000321222600005
  • scopus:84879677633
ISSN
1553-7404
DOI
10.1371/journal.pgen.1003500
language
English
LU publication?
yes
id
6051a175-1e32-46ca-8400-25ae637bc3ab (old id 4112594)
date added to LUP
2013-11-07 14:22:44
date last changed
2019-02-20 01:59:02
@article{6051a175-1e32-46ca-8400-25ae637bc3ab,
  abstract     = {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&lt;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&lt;5x10(-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.},
  articleno    = {e1003500},
  author       = {Randall, Joshua C. and Winkler, Thomas W. and Kutalik, Zoltan and Berndt, Sonja I. and Jackson, Anne U. and Monda, Keri L. and Kilpelaeinen, Tuomas O. and Esko, Tonu and Maegi, Reedik and Li, Shengxu and Workalemahu, Tsegaselassie and Feitosa, Mary F. and Croteau-Chonka, Damien C. and Day, Felix R. and Fall, Tove and Ferreira, Teresa and Gustafsson, Stefan and Locke, Adam E. and Mathieson, Iain and Scherag, Andre and Vedantam, Sailaja and Wood, Andrew R. and Liang, Liming and Steinthorsdottir, Valgerdur and Thorleifsson, Gudmar and Dermitzakis, Emmanouil T. and Dimas, Antigone S. and Karpe, Fredrik and Min, Josine L. and Nicholson, George and Clegg, Deborah J. and Person, Thomas and Krohn, Jon P. and Bauer, Sabrina and Buechler, Christa and Eisinger, Kristina and Bonnefond, Amelie and Froguel, Philippe and Hottenga, Jouke-Jan and Prokopenko, Inga and Waite, Lindsay L. and Harris, Tamara B. and Smith, Albert Vernon and Shuldiner, Alan R. and McArdle, Wendy L. and Caulfield, Mark J. and Munroe, Patricia B. and Gronberg, Henrik and Chen, Yii-Der Ida and Li, Guo and Beckmann, Jacques S. and Johnson, Toby and Thorsteinsdottir, Unnur and Teder-Laving, Maris and Khaw, Kay-Tee and Wareham, Nicholas J. and Zhao, Jing Hua and Amin, Najaf and Oostra, Ben A. and Kraja, Aldi T. and Province, Michael A. and Cupples, L. Adrienne and Heard-Costa, Nancy L. and Kaprio, Jaakko and Ripatti, Samuli and Surakka, Ida and Collins, Francis S. and Saramies, Jouko and Tuomilehto, Jaakko and Jula, Antti and Salomaa, Veikko and Erdmann, Jeanette and Hengstenberg, Christian and Loley, Christina and Schunkert, Heribert and Lamina, Claudia and Wichmann, H. Erich and Albrecht, Eva and Gieger, Christian and Hicks, Andrew A. and Johansson, Asa and Pramstaller, Peter P. and Kathiresan, Sekar and Speliotes, Elizabeth K. and Penninx, Brenda and Hartikainen, Anna-Liisa and Jarvelin, Marjo-Riitta and Gyllensten, Ulf and Boomsma, Dorret I. and Campbell, Harry and Wilson, James F. and Chanock, Stephen J. and Farrall, Martin and Goel, Anuj and Medina-Gomez, Carolina and Rivadeneira, Fernando and Estrada, Karol and Uitterlinden, Andre G. and Hofman, Albert and Zillikens, M. Carola and den Heijer, Martin and Kiemeney, Lambertus A. and Maschio, Andrea and Hall, Per and Tyrer, Jonathan and Teumer, Alexander and Voelzke, Henry and Kovacs, Peter and Toenjes, Anke and Mangino, Massimo and Spector, Tim D. and Hayward, Caroline and Rudan, Igor and Hall, Alistair S. and Samani, Nilesh J. and Attwood, Antony Paul and Sambrook, Jennifer G. and Hung, Joseph and Palmer, Lyle J. and Lokki, Marja-Liisa and Sinisalo, Juha and Boucher, Gabrielle and Huikuri, Heikki and Lorentzon, Mattias and Ohlsson, Claes and Eklund, Niina and Eriksson, Johan G. and Barlassina, Cristina and Rivolta, Carlo and Nolte, Ilja M. and Snieder, Harold and Van der Klauw, Melanie M. and Van Vliet-Ostaptchouk, Jana V. and Gejman, Pablo V. and Shi, Jianxin and Jacobs, Kevin B. and Wang, Zhaoming and Bakker, Stephan J. L. and Leach, Irene Mateo and Navis, Gerjan and van der Harst, Pim and Martin, Nicholas G. and Medland, Sarah E. and Montgomery, Grant W. and Yang, Jian and Chasman, Daniel I. and Ridker, Paul M. and Rose, Lynda M. and Lehtimaki, Terho and Raitakari, Olli and Absher, Devin and Iribarren, Carlos and Basart, Hanneke and Hovingh, Kees G. and Hyppoenen, Elina and Power, Chris and Anderson, Denise and Beilby, John P. and Hui, Jennie and Jolley, Jennifer and Sager, Hendrik and Bornstein, Stefan R. and Schwarz, Peter E. H. and Kristiansson, Kati and Perola, Markus and Lindstrom, Jaana and Swift, Amy J. and Uusitupa, Matti and Atalay, Mustafa and Lakka, Timo A. and Rauramaa, Rainer and Bolton, Jennifer L. and Fowkes, Gerry and Fraser, Ross M. and Price, Jackie F. and Fischer, Krista and KrjutAikov, Kaarel and Metspalu, Andres and Mihailov, Evelin and Langenberg, Claudia and Luan, Jian'an and Ong, Ken K. and Chines, Peter S. and Keinanen-Kiukaanniemi, Sirkka M. and Saaristo, Timo E. and Edkins, Sarah and Franks, Paul and Hallmans, Goran and Shungin, Dmitry and Morris, Andrew David and Palmer, Colin N. A. and Erbel, Raimund and Moebus, Susanne and Noethen, Markus M. and Pechlivanis, Sonali and Hveem, Kristian and Narisu, Narisu and Hamsten, Anders and Humphries, Steve E. and Strawbridge, Rona J. and Tremoli, Elena and Grallert, Harald and Thorand, Barbara and Illig, Thomas and Koenig, Wolfgang and Mueller-Nurasyid, Martina and Peters, Annette and Boehm, Bernhard O. and Kleber, Marcus E. and Maerz, Winfried and Winkelmann, Bernhard R. and Kuusisto, Johanna and Laakso, Markku and Arveiler, Dominique and Cesana, Giancarlo and Kuulasmaa, Kari and Virtamo, Jarmo and Yarnell, John W. G. and Kuh, Diana and Wong, Andrew and Lind, Lars and de Faire, Ulf and Gigante, Bruna and Magnusson, Patrik K. E. and Pedersen, Nancy L. and Dedoussis, George and Dimitriou, Maria and Kolovou, Genovefa and Kanoni, Stavroula and Stirrups, Kathleen and Bonnycastle, Lori L. and Njolstad, Inger and Wilsgaard, Tom and Ganna, Andrea and Rehnberg, Emil and Hingorani, Aroon and Kivimaki, Mika and Kumari, Meena and Assimes, Themistocles L. and Barroso, Ine S. and Boehnke, Michael and Borecki, Ingrid B. and Deloukas, Panos and Fox, Caroline S. and Frayling, Timothy and Groop, Leif and Haritunians, Talin and Hunter, David and Ingelsson, Erik and Kaplan, Robert and Mohlke, Karen L. and O'Connell, Jeffrey R. and Schlessinger, David and Strachan, David P. and Stefansson, Kari and van Duijn, Cornelia M. and Abecasis, Goncalo R. and McCarthy, Mark I. and Hirschhorn, Joel N. and Qi, Lu and Loos, Ruth J. F. and Lindgren, Cecilia M. and North, Kari E. and Heid, Iris M.},
  issn         = {1553-7404},
  language     = {eng},
  number       = {6},
  publisher    = {Public Library of Science},
  series       = {PLoS Genetics},
  title        = {Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits},
  url          = {http://dx.doi.org/10.1371/journal.pgen.1003500},
  volume       = {9},
  year         = {2013},
}