Given the clear gender dimorphism of central obesity, and evidence that some genetic effects on fat distribution may be gender-specific [7], we reanalysed the stage 1 GWAS data, looking for effects restricted to males or females only. These analyses revealed a further locus of interest. SNPs, including rs2605100, within a gene desert on chromosome 1q41 (138 kb from ZC3H11B and 259 kb from LYPLAL1, encoding lysophospholipase-like protein 1) had shown modest evidence for association with WHR in our primary (both genders included) analysis (P = 3.6×10−6) (Table S2). However, in gender-specific analyses, this association was clearly restricted to females (P = 1.3×10−8; males: P = 0.50). When stage 1 and stage 2 data were combined, the female-only signal remained highly-significant (P = 2.6×10−8) (Table 1) with evidence of effect-size heterogeneity between genders (P = 1.1×10−3). As the CHARGE GWAS analyses were restricted to WC, we were unable to follow-up the LYPLAL1 signal in these data.
