rs9217

This association study screened 93 SNPs in 19 cholinergic genes (CHAT, CHRM1-5, CHRNA1-7, CHRNA9-10, CHRNB1-4) in two bipolar disorder (BD) pedigree series: NIMH Genetics Initiative (474 samples, 152 families) and Clinical Neurogenetics (83 samples, 22 families). Sib-TDT analysis showed nominally significant association for four SNPs (CHRNA2 rs7017417 P=0.024, CHRNA5 rs514743 P=0.031, CHRNB1 rs2302762 P=0.049, CHRNB4 rs1948 P=0.031), but none reached gene-wide significance after multiple testing correction. The authors conclude that these 19 cholinergic genes are unlikely to play a major role in BD predisposition in these pedigrees.

This gene-based association study examined 2,037 subjects from 602 nuclear families of African-American and European-American origin to determine if variants in the CHRNB1 (nicotinic acetylcholine receptor β1 subunit) and CHRM1 (M1 muscarinic acetylcholine receptor) genes are associated with nicotine dependence. CHRNB1 showed significant association with nicotine dependence measures, particularly haplotype A-T-A (formed by rs2302765, rs2302762, and rs9217) in African-Americans (P = 0.006-0.009 for multiple measures) and haplotype A-T-A (rs2302765, rs2302763, rs9217) in European-Americans (P = 0.005-0.016). CHRM1 haplotype C-C-A-T-G-G showed protective associations in African-Americans (P = 0.008-0.013).