No evidence for association between 19 cholinergic genes and bipolar disorder

Abstract

Cholinergic dysfunction has been proposed for the pathogenesis of bipolar disorder (BD), and we have therefore performed a systematic association study of cholinergic system genes in BD (including schizoaffective disorder bipolar type). We genotyped 93 single nucleotide polymorphisms (SNPs) in 19 genes (CHAT, CHRM1‐5, CHRNA1‐7, CHRNA9, CHRNA10, and CHRNB1‐4) in two series of samples: the National Institute of Mental Health (NIMH) Genetics Initiative pedigrees with 474 samples from 152 families, and the Clinical Neurogenetics (CNG) pedigrees with 83 samples from 22 multiplex families. Sib‐transmission/disequilibrium test (sib_TDT) analysis showed nominally significant transmission bias for four SNPs (CHRNA2: rs7017417, P = 0.024; CHRNA5: rs514743, P = 0.031; CHRNB1: rs2302762, P = 0.049; CHRNB4: rs1948, P = 0.031). Haploview analyses showed nominally significant transmission bias of several haplotypes in CHRNA2, CHRNA7, CHRNB1, and CHRNB4, respectively. However, none of these associations reached gene‐wide significance after correction by permutation. Alcohol dependence (including alcohol abuse) was not a significant covariate in the present genetic association analysis. Thus, it is unlikely that these 19 cholinergic genes play a major role in the pre‐disposition to BD in these pedigrees.