TY - JOUR
T1 - Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
AU - MAGIC
AU - Heid, Iris M.
AU - Jackson, Anne U.
AU - Randall, Joshua C.
AU - Winkler, Thomas W.
AU - Qi, Lu
AU - Steinthorsdottir, Valgerdur
AU - Thorleifsson, Gudmar
AU - Zillikens, M. Carola
AU - Speliotes, Elizabeth K.
AU - Maegi, Reedik
AU - Workalemahu, Tsegaselassie
AU - White, Charles C.
AU - Bouatia-Naji, Nabila
AU - Harris, Tamara B.
AU - Berndt, Sonja I.
AU - Ingelsson, Erik
AU - Willer, Cristen J.
AU - Weedon, Michael N.
AU - Luan, Jianan
AU - Vedantam, Sailaja
AU - Esko, Tonu
AU - Kilpelaeinen, Tuomas O.
AU - Kutalik, Zoltan
AU - Li, Shengxu
AU - Monda, Keri L.
AU - Dixon, Anna L.
AU - Holmes, Christopher C.
AU - Kaplan, Lee M.
AU - Liang, Liming
AU - Min, Josine L.
AU - Moffatt, Miriam F.
AU - Molony, Cliona
AU - Nicholson, George
AU - Schadt, Eric E.
AU - Zondervan, Krina T.
AU - Feitosa, Mary F.
AU - Ferreira, Teresa
AU - Allen, Hana Lango
AU - Weyant, Robert J.
AU - Wheeler, Eleanor
AU - Wood, Andrew R.
AU - Estrada, Karol
AU - Goddard, Michael E.
AU - Lettre, Guillaume
AU - Visscher, Peter M.
AU - Campbell, Harry
AU - Wild, Sarah H.
AU - Zgaga, Lina
AU - Rudan, Igor
AU - Wilson, James F.
PY - 2010/11
Y1 - 2010/11
N2 - Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
AB - Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
UR - http://www.scopus.com/inward/record.url?scp=78049349396&partnerID=8YFLogxK
U2 - 10.1038/ng.685
DO - 10.1038/ng.685
M3 - Article
C2 - 20935629
SN - 1061-4036
VL - 42
SP - 949-U160
JO - Nature Genetics
JF - Nature Genetics
IS - 11
ER -