For a single GSV, however, the association with obesity was strongly replicated. A deletion of 220 kb on chromosome 16p11.2 (at 28.73–28.95 Mb) affecting several genes including SH2B1, was identified in 6 obese individuals compared to none in normal weight subjects (P = 5.48×10−4). This deletion spans a locus implicated in obesity in SNP-association studies [14]. Of note, apart from rare instances of more extensive deletions spanning both regions [10], [21], which complicated the previous analysis of this region (see Text S1), this 220 kb region is completely separate from the 593 kb locus (also on 16p11.2) whose association with obesity/underweight has been previously reported by us [12], [13]; they are 600 kb apart, there is no discernible linkage disequilibrium between SNPs within each region (Figure S1), and copy-number changes at the 593 kb locus have no consistent effect on expression of genes at the 220 kb locus [13]. Thus, each locus is independently associated with obesity.
