期刊
HUMAN HEREDITY
卷 57, 期 2, 页码 59-68出版社
KARGER
DOI: 10.1159/000077543
关键词
acetylcholine; linkage; nicotinic receptor; linkage; genetics; permutation testing; candidate genes
资金
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH059624, R01MH041874, R37MH043518, U01MH046318, U01MH046289, R01MH044292, U01MH046276, R01MH043518, R25MH060485] Funding Source: NIH RePORTER
- NIMH NIH HHS [U01 MH 46289, U01 MH 46276, R01 MH 41874-01, R25 MH 60485, R01 MH 44292, R01 MH 59624, R01 MH 60485, 5U01 MH 46318, R01 MH43518, 1R37 MH 43518] Funding Source: Medline
Smoking is a common correlate of schizophrenia, which leads to medical morbidity. Although twin and adoption studies have consistently implicated genes in the etiology of both smoking and schizophrenia, finding genes has been difficult. Several authors have suggested that clinical or neurobiological features associated with schizophrenia, such as smoking, might improve the ability to detect schizophrenia susceptibility genes by identifying genes related to the etiology of that feature. The objective of this study is to assess evidence for linkage of sixteen nicotinic acetylcholine receptor genes and smoking in schizophrenia families, using data from the NIMH Genetics Initiative for schizophrenia. Sixteen nicotinic acetylcholine receptor genes were selected prior to analysis. We used a multipoint sibling pair linkage analysis program, SIBPAL2, with a smoking trait in schizophrenia families. The significance of the group of candidate genes, in addition to each individual candidate gene, was assessed using permutation testing, which adjusted for multiple comparisons. The group of genes showed significant linkage to the smoking trait after adjusting for multiple comparisons through permutation testing (p = 0.039). In addition, two of the individual candidate genes were significant (CHRNA2, p = 0.044) and (CHRNB2, p = 0.015) and two genes were marginally significant (CHRNA7, p = 0.095; CHRNA1, p = 0.076). The significance of the complex hypothesis, involving sixteen genes, implicates the nicotinic system in smoking for schizophrenic families. Individual gene analysis suggests that CHRNA2 and CHRNB2 may play a particular role in this involvement. Such findings help prioritize genes for future case control studies. In addition, we provide a novel permutation method that is useful in future analyses involving a single hypothesis, with multiple candidate genes. Copyright (C) 2004 S. Karger AG, Basel.
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