No evidence for association between 19 cholinergic genes and bipolar disorder

Am J Med Genet B Neuropsychiatr Genet. 2007 Sep 5;144B(6):715-23. doi: 10.1002/ajmg.b.30417.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Bipolar Disorder / genetics*
  • Choline O-Acetyltransferase / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Pedigree
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Receptors, Cholinergic / genetics*

Substances

  • Receptors, Cholinergic
  • Choline O-Acetyltransferase