Methylomic profiling and replication implicates deregulation of PCSK9 in alcohol use disorder.

ABSTRACT: Alcohol use disorder (AUD) is a common and chronic disorder with substantial effects on personal and public health. The underlying pathophysiology is poorly understood but strong evidence suggests significant roles of both genetic and epigenetic components. Given that alcohol affects many organ systems, we performed a cross-tissue and cross-phenotypic analysis of genome-wide methylomic variation in AUD using samples from 3 discovery, 4 replication, and 2 translational cohorts. We identified a differentially methylated region in the promoter of the proprotein convertase subtilisin/kexin 9 (PCSK9) gene that was associated with disease phenotypes. Biological validation showed that PCSK9 promoter methylation is conserved across tissues and positively correlated with expression. Replication in

SUBMITTER: Lohoff FW 

PROVIDER: S-EPMC5832488 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature