TY - JOUR
T1 - Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits
AU - Randall, Joshua C
AU - Winkler, Thomas W
AU - Kutalik, Zoltán
AU - Berndt, Sonja I
AU - Jackson, Anne U
AU - Monda, Keri L
AU - Kilpeläinen, Tuomas O
AU - Esko, Tõnu
AU - Mägi, Reedik
AU - Li, Shengxu
AU - Workalemahu, Tsegaselassie
AU - Feitosa, Mary F
AU - Croteau-Chonka, Damien C
AU - Day, Felix R
AU - Fall, Tove
AU - Ferreira, Teresa
AU - Gustafsson, Stefan
AU - Locke, Adam E
AU - Mathieson, Iain
AU - Scherag, Andre
AU - Vedantam, Sailaja
AU - Wood, Andrew R
AU - Liang, Liming
AU - Steinthorsdottir, Valgerdur
AU - Thorleifsson, Gudmar
AU - Dermitzakis, Emmanouil T
AU - Dimas, Antigone S
AU - Karpe, Fredrik
AU - Min, Josine L
AU - Nicholson, George
AU - Clegg, Deborah J
AU - Person, Thomas
AU - Krohn, Jon P
AU - Bauer, Sabrina
AU - Buechler, Christa
AU - Eisinger, Kristina
AU - Bonnefond, Amélie
AU - Froguel, Philippe
AU - Hottenga, Jouke-Jan
AU - Prokopenko, Inga
AU - Waite, Lindsay L
AU - Harris, Tamara B
AU - Smith, Albert Vernon
AU - Shuldiner, Alan R
AU - McArdle, Wendy L
AU - Caulfield, Mark J
AU - Munroe, Patricia B
AU - Grönberg, Henrik
AU - van der Harst, Pim
AU - Basart, Hanneke
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - Anthropometry/methods
KW - Body Height/genetics
KW - Body Mass Index
KW - Body Weight/genetics
KW - Body Weights and Measures
KW - Female
KW - Genetic Loci
KW - Genome, Human
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Sex Characteristics
KW - Waist Circumference/genetics
KW - Waist-Hip Ratio
U2 - 10.1371/journal.pgen.1003500
DO - 10.1371/journal.pgen.1003500
M3 - Article
C2 - 23754948
SN - 1553-7390
VL - 9
SP - e1003500
JO - PLoS Genetics
JF - PLoS Genetics
IS - 6
ER -