rs1672717

This association study examined 3,564 subjects from the SAGE dataset (2,428 European-American, 1,136 African-American) to determine associations between 88 variants in HTR3A, HTR3B, and SLC6A4 genes and alcohol, cocaine, and nicotine dependence. Individual SNP analysis found rs2066713 in SLC6A4 significantly associated with FTND in African-Americans (beta = -1.39, P = 1.6E-04). Haplotype analysis identified major haplotypes in HTR3B and HTR3A significantly associated with alcohol dependence and FTND. GMDR interaction analysis revealed significant SNP-by-SNP interactions within these three genes affecting multiple addictive phenotypes.

This case-control association study examined 22 SNPs in HTR3A, HTR3B, and SLC6A4 genes in relation to alcohol dependence in 500 cases and 280 controls of European descent. Low-frequency variants rs33940208 (HTR3A) and rs2276305 (HTR3B) showed protective effects (OR=0.212, P=0.004 and OR=0.261, P=0.016 respectively). Gene-by-gene interaction analyses revealed significant interactive effects among SLC6A4, HTR3A, and HTR3B variants on alcohol dependence risk (OR=2.71-3.095, P<0.001-2×10⁻⁴). Findings were replicated in 6,699 samples from the OZ-ALC-GWAS study.