No evidence for association between 19 cholinergic genes and bipolar disorder.
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.
Shi
Jiajun
J
Department of Psychiatry, The University of Chicago, Chicago, Illinois 60637, USA.
Hattori
Eiji
E
Zou
Hongwei
H
Badner
Judith A
JA
Christian
Susan L
SL
Gershon
Elliot S
ES
Liu
Chunyu
C
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D002795:Choline O-Acetyltransferase / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011950:Receptors, Cholinergic / Q000235:genetics*
D011950:Receptors, Cholinergic; D002795:Choline O-Acetyltransferase