Genomewide association study of cocaine dependence and related traits: FAM53B identified as a risk gene

Abstract

We report a GWAS for cocaine dependence (CD) in three sets of African- and European-American subjects (AAs and EAs, respectively), to identify pathways, genes, and alleles important in CD risk.

The discovery GWAS dataset (n=5,697 subjects) was genotyped using the Illumina OmniQuad microarray (890,000 analyzed SNPs). Additional genotypes were imputed based on the 1000 Genomes reference panel. Top-ranked findings were evaluated by incorporating information from publicly available GWAS data from 4,063 subjects. Then, the most significant GWAS SNPs were genotyped in 2,549 independent subjects.

We observed one genomewide-significant (GWS) result: rs7086629 at the FAM53B (“family with sequence similarity 53, member B”) locus. This was supported in both AAs and EAs; p-value (meta-analysis of all samples) =4.28×10 ⁻⁸. The gene maps to the same chromosomal region as the maximum peak we observed in a previous linkage study. NCOR2 (nuclear receptor corepressor 1) SNP rs150954431 was associated with p=1.19×10 ⁻⁹ in the EA discovery sample. SNP rs2456778, which maps to CDK1 (“cyclin-dependent kinase 1”), was associated with cocaine-induced paranoia in AAs in the discovery sample only (p=4.68×10 ⁻⁸).

This is the first study to identify risk variants for CD using GWAS. Our results implicate novel risk loci and provide insights into potential therapeutic and prevention strategies.