Leveraging cross-species transcription factor binding site patterns: from diabetes risk loci to disease mechanisms.

ABSTRACT: Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation with a complexity assessment of co-occurring transcription factor binding sites (TFBS) can identify cis-regulatory variants and elucidate their mechanistic role in disease. Analysis of established type 2 diabetes risk loci revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1 homeobox factor as a repressor of PPARG2 expression in adipose cells and demonstrate its adverse

SUBMITTER: Claussnitzer M 

PROVIDER: S-EPMC7116609 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature