Genetic Association Studies of Alcohol Dependence

Objectives: Alcohol dependence (AD) commonly co-occurs with bipolar disorder (BP) and schizophrenia (SZ). Together these heritable (and cross-heritable disorders) account for significant morbidity and mortality. The genetic comorbidity between AD, BP, and SZ was investigated to find genetic factors affecting risk for developing AD. / Methods: Subjects were from the UCL AD (n=586), BP, and SZ samples and supernormal controls (SNC; up to 603 subjects). The BP and SCZ subjects were further categorized as having comorbid AD (BPALC n=143; SZALC n=77) or without AD comorbidity (BPnonALC n=367; SZnonALC n=384). The following single gene association study or Genome-Wide Association Studies (GWAS) of the above phenotypes were performed: i) Seven SNPs previously associated with AD in the GABRA2 gene were genotyped in the AD cases and SNCs. ii) GWAS of BPALC vs SNC; and BPALC vs BPnonALC. iii) GWAS of SZALC vs SNC; and SZALC vs SZnonALC. iv) Meta-analysis of BPALC and SZALC GWAS data. Single marker tests, and gene-based permutation tests on all SNPs within a 50kb region flanking each gene, were performed. Genes previously implicated with AD and related phenotypes were tested for association in the datasets. Pathways analysis were performed on all genes uncorrected p