Very low-depth sequencing in a founder population identifies a cardioprotective APOC3 signal missed by genome-wide imputation.

ABSTRACT: Cohort-wide very low-depth whole-genome sequencing (WGS) can comprehensively capture low-frequency sequence variation for the cost of a dense genome-wide genotyping array. Here, we analyse 1x sequence data across the APOC3 gene in a founder population from the island of Crete in Greece (n = 1239) and find significant evidence for association with blood triglyceride levels with the previously reported R19X cardioprotective null mutation (β = -1.09,σ = 0.163, P = 8.2 × 10^-11) and a second loss of function mutation, rs138326449 (β = -1.17,σ = 0.188, P = 1.14 × 10^-9). The signal cannot be recapitulated by imputing genome-wide genotype data on a large reference panel of 5122 individuals including 249 with 4x WGS data from the same population. Gene-level meta-analysis with

SUBMITTER: Gilly A 

PROVIDER: S-EPMC5081052 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature