Biological constraints on GWAS SNPs at suggestive significance thresholds reveal additional BMI loci.

ABSTRACT: To uncover novel significant association signals (p<5×10^-8), genome-wide association studies (GWAS) requires increasingly larger sample sizes to overcome statistical correction for multiple testing. As an alternative, we aimed to identify associations among suggestive signals (5 × 10^-8≤p<5×10^-4) in increasingly powered GWAS efforts using chromatin accessibility and direct contact with gene promoters as biological constraints. We conducted retrospective analyses of three GIANT BMI GWAS efforts using ATAC-seq and promoter-focused Capture C data from human adipocytes and embryonic stem cell (ESC)-derived hypothalamic-like neurons. This approach, with its extremely low false-positive rate, identified 15 loci at p<5×10^-5 in the 2010 GWAS, of which 13

SUBMITTER: Hammond RK 

PROVIDER: S-EPMC7815306 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature