As for quantitative traits, we illustrated the effectiveness of CAUSALdb fine-mapping results by taking body mass index (BMI) as example. In the 31 collected GWASs of BMI for EUR population, genetic locus 16q12.2 was found containing potential causal variants in most studies (29, 93.5%). The credible set variants of these studies at this locus all lie in the first intron of FTO gene. Notably two potential causal variants in perfect LD, rs1558902 and rs1421085, were found in credible sets of 18 and 14 BMI studies, respectively, which are far more than only six studies involving the third one rs9937053, indicating the significance of functional follow-up to dissect their biological mechanism. The variant rs1421085 has been proven to repress mitochondrial thermogenesis in adipocyte precursor cells by disrupting a conserved motif for the ARID5B repressor and affecting IRX3 and IRX5 enhancer activity (53). Taken together, CAUSALdb offers a comprehensive knowledgebase to fine-map potential causal variants that confer susceptibility to complex traits/diseases.
