Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits
Journal article
Randall, J., Winkler, T.W., Kutalik, Z., Berndt, S.I., Jackson, Anne, Monda, K.L., Kilpelainen, Tuomas, Esko, Tonu, Magi, Reedik, Li, Shengxu, Workalemahu, T., Feitosa, Mary, Croteau-Chonka, D.C., Lorentzon, Karl Mattias, Day, Felix, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, A.E., ... al, et. (2013). Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits. PLoS Genetics. 9(6), pp. 1-19. https://doi.org/10.1371/journal.pgen.1003500
Authors | Randall, J., Winkler, T.W., Kutalik, Z., Berndt, S.I., Jackson, Anne, Monda, K.L., Kilpelainen, Tuomas, Esko, Tonu, Magi, Reedik, Li, Shengxu, Workalemahu, T., Feitosa, Mary, Croteau-Chonka, D.C., Lorentzon, Karl Mattias, Day, Felix, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, A.E., Mathieson, Iain, Scherag, Andre, Vedantam, S., Wood, Andrew, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T., Dimas, A.S., Karpe, F., Min, Josine, Nicholson, George, Clegg, Deborah J., Person, Thomas, Krohn, Jon, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina and al, et |
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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<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. |
Keywords | sex differences; genome-wide search; genetic effects; anthropometric traits |
Year | 01 Jan 2013 |
Journal | PLoS Genetics |
Journal citation | 9 (6), pp. 1-19 |
Publisher | Public Library of Science |
ISSN | 1553-7390 |
Digital Object Identifier (DOI) | https://doi.org/10.1371/journal.pgen.1003500 |
Web address (URL) | https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003500#abstract0 |
Open access | Published as ‘gold’ (paid) open access |
Research or scholarly | Research |
Page range | 1-19 |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 06 Jun 2013 |
Publication process dates | |
Accepted | 15 Mar 2013 |
Deposited | 13 Aug 2024 |
Additional information | Funding for this study was provided by multiple sources, see article for details. |
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. | |
Supplementary material (20 files) available at: | |
Place of publication | United States |
https://acuresearchbank.acu.edu.au/item/90833/sex-stratified-genome-wide-association-studies-including-270-000-individuals-show-sexual-dimorphism-in-genetic-loci-for-anthropometric-traits
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OA_Lorentzon_2013_Sex_stratified_genome_wide_association_studies.pdf | |
License: CC0 | |
File access level: Open |
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