A functional genomics pipeline identifies pleiotropy and cross-tissue effects within obesity-associated GWAS loci.

ABSTRACT: Genome-wide association studies (GWAS) have identified many disease-associated variants, yet mechanisms underlying these associations remain unclear. To understand obesity-associated variants, we generate gene regulatory annotations in adipocytes and hypothalamic neurons across cellular differentiation stages. We then test variants in 97 obesity-associated loci using a massively parallel reporter assay and identify putatively causal variants that display cell type specific or cross-tissue enhancer-modulating properties. Integrating these variants with gene regulatory information suggests genes that underlie obesity GWAS associations. We also investigate a complex genomic interval on 16p11.2 where two independent loci exhibit megabase-range, cross-locus chromatin interactions. We demonstrat

SUBMITTER: Joslin AC 

PROVIDER: S-EPMC8421397 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature