CNVR 1p31.1 (Table 2) 20 kb upstream of NEGR1 was the only CNV associated with BMI in a meta-analysis of 15 GWAS (8). Identification of the CNV was based on SNP tagging in a large meta-analysis of population-based samples of European origin. We were able to confirm this CNVR in both of our GWAS discovery samples (min. Pfamily-based = 0.0084; min. Pcc = 0.0068 for different CNV markers) while we observed stronger signals in the family-based GWAS sample (Fig. 4). Moreover, CNVR 1p31.1 is one of the two CNVRs (out of 20) that could be tagged by an SNP (rs2815752). The major allele T of rs2815752 is tagging the deletion allele of CNVR 1p31.1. Analysis of the CNVR-tagging SNP in the replication sample (365 independent obesity trios) again underlined the obesity association (OR = 1.277; 95% CI = 1.021–1.597; one-sided P-value = 0.0157; Table 3). In a joint analysis of the two family-based samples at rs2815752, we estimated an OR of 1.214 (95% CI = 1.046–1.408, one-sided P-value = 0.0052). Additional support for this CNVR was provided by the array-based replication analysis (see above).
