Complex regulatory interactions at <i>GDF5</i> shape joint morphology and osteoarthritis disease risk.

ABSTRACT: Our ability to pinpoint causal variants using GWAS is dependent on understanding the dynamic epigenomic and epistatic context of each associated locus. Being the best studied skeletal locus, GDF5 associates with many diseases and has a complex cis-regulatory architecture. We interrogate GDF5 regulatory interactions and model disease variants in vitro and in vivo. For all regulatory regions we see that local epigenetic activation/repression impacts patterns of joint-specific expression and disease risk. By modeling the most cited risk variant in mice we found that it had no impact on expression, joint morphology, or disease. Yet, we identified significant epistatic expression interactions between this risk variant and others lying within regulatory regions subjec

SUBMITTER: Coveney CR 

PROVIDER: S-EPMC11565913 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature