Genome-wide polygenic risk score for major osteoporotic fractures in postmenopausal women using associated single nucleotide polymorphisms.

ABSTRACT:

Background

Osteoporosis is highly polygenic and heritable, with heritability ranging from 50 to 80%; most inherited susceptibility is associated with the cumulative effect of many common genetic variants. However, existing genetic risk scores (GRS) only provide a few percent predictive power for osteoporotic fracture.

Methods

We derived and validated a novel genome-wide polygenic score (GPS) comprised of 103,155 common genetic variants to quantify this susceptibility and tested this GPS prediction ability in an independent dataset (n = 15,776).

Results

Among postmenopausal women, we found a fivefold gradient in the risk of major osteoporotic fracture (MOF) (p < 0.001) and a 15.25-fold increased risk of severe osteoporosis (p < 0.001) across the GPS deciles. Compared w

SUBMITTER: Wu Q 

PROVIDER: S-EPMC9933300 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature