In contrast, the signal on chromosome 1q41 (near LYPLAL1) showed relatively modest associations with overall obesity (stage 2, women only, P = 1.9×10−4 for BMI) and WC (P = 0.01). Crucially, the strength of the association with WHR was substantially greater after adjustment for BMI (stage 2, women only, P = 4.3×10−6). In the limited subset of women (N = 7,228) for whom direct measures of hip circumference (HC) could be retrieved, and in whom there was a proportionate signal for WHR (P = 5.2×10−4), we found no association with HC (P = 0.7) and a directionally consistent trend of association to WC (P = 0.06). Whilst these data would suggest that the LYPLAL1 signal does indeed have a specific effect on fat distribution, our own DXA data on regional fat distribution are non-contributory (N = 5,455) (Table S7), and large-scale clinical imaging studies will be required to explore this further. The obvious candidate within this locus (although it lies ∼259 kb downstream of the most strongly-associated variant) is LYPLAL1. This gene encodes a lysophospholipase-like 1 protein thought to act as a triglyceride lipase and reported to be up-regulated in subcutaneous adipose tissue of obese subjects [25].
