MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk.

ABSTRACT: A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset of the Nord-Trøndelag Health Study, followed by imputation in the remaining sample (N = 19,705), and identified ten known BMD loci. However, one previously unreported variant, LoF mutation in MEPE, p.(Lys70IlefsTer26, minor allele frequency [MAF] = 0.8%), was associated with decreased ultradistal forearm BMD (P-value = 2.1 × 10^-18), and increased osteoporosis (P-value = 4.2 × 10^-5) and fracture risk (P-value = 1.6 × 10^-5). The MEPE LoF association with BMD and fractu

SUBMITTER: Surakka I 

PROVIDER: S-EPMC7585430 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature