Another advantage of a single large cohort, such as GERA, is the ability to directly assess additional local SNPs by conditional analysis. The absence of individual-level data requires LD assumptions from other studies. Nevertheless, we only found two additional variants in GERA that were ultimately not explained by nearby previously-described SNPs, and an additional four when combining GERA and UKB. We further note these additional conditional hits were located at a substantial distance from the locus sentinel SNP, likely indicating an independent gene and/or mechanism involved. The lack of identification of additional SNPs close to sentinel SNPs is quite distinct from what is observed for serum lipids, for example38, and suggests that lower frequency variants with larger effects within the same loci identified here are uncommon. A similar conclusion was recently obtained in a sequencing study of type 2 diabetes39.
