期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
卷 144B, 期 6, 页码 715-723出版社
WILEY-LISS
DOI: 10.1002/ajmg.b.30417
关键词
single nucleotide polymorphism; linkage disequilibrium; haplotype; bipolar disorder; cholinergic
资金
- NIMH NIH HHS [R01 MH061613, MH065560-02, MH61613-05A1, R01 MH065560-05, U01 MH046282-04, R01 MH065560, R01 MH061613-08] Funding Source: Medline
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. (c) 2007 Wiley-Liss, Inc.
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