Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height.

ABSTRACT: The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P <  6×10-10 after conditioning on previously reported variants, with effect sizes ranging from -7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based

SUBMITTER: Hawkes G 

PROVIDER: S-EPMC11450065 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature