Genome-wide meta-analysis identifies a novel susceptibility signal at CACNA2D3 for nicotine dependence.

ABSTRACT: Nicotine dependence (ND) has a reported heritability of 40-70%. Low-coverage whole-genome sequencing was conducted in 1,889 samples from the UCSF Family study. Linear mixed models were used to conduct genome-wide association (GWA) tests of ND in this and five cohorts obtained from the database of Genotypes and Phenotypes. Fixed-effect meta-analysis was carried out separately for European (n?=?14,713) and African (n?=?3,369) participants, and then in a combined analysis of both ancestral groups. The meta-analysis of African participants identified a significant and novel susceptibility signal (rs56247223; p?=?4.11?×?10-8 ). Data from the Genotype-Tissue Expression (GTEx) study suggested the protective allele is associated with reduced mRNA expression of CACNA2D3 in three human brain tissues (p?

SUBMITTER: Yin X 

PROVIDER: S-EPMC5656555 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature