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In the present study, we aimed to test the associations between rare variants at<jats:italic>CHRN<\/jats:italic>genes and nicotine dependence (ND), and alcohol dependence (AD). A total of 26,498 subjects with nine different neuropsychiatric disorders in 15 independent cohorts, which were genotyped on Illumina, Affymetrix, or PERLEGEN microarray platforms, were analyzed. Associations between rare variants (minor allele frequency (MAF) &lt;0.05) at<jats:italic>CHRN<\/jats:italic>genes and nicotine dependence, and alcohol dependence were tested. The mRNA expression of all<jats:italic>Chrn<\/jats:italic>genes in whole mouse brain and 10 specific brain areas was investigated. All<jats:italic>CHRN<\/jats:italic>genes except the muscle\u2010type<jats:italic>CHRNB<\/jats:italic>1, including eight genomic regions containing 11 neuronal<jats:italic>CHRN<\/jats:italic>genes and three genomic regions containing four muscle\u2010type<jats:italic>CHRN<\/jats:italic>genes, were significantly associated with ND, and\/or AD. All of these genes were expressed in the mouse brain. We conclude that<jats:italic>CHRNs<\/jats:italic>are associated with ND (mainly) and AD, supporting the hypothesis that the full catalog of ND\/AD risk genes may contain most neuronal nAChRs\u2010encoding genes. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32476","type":"journal-article","created":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T13:14:35Z","timestamp":1471007675000},"page":"1057-1071","source":"Crossref","is-referenced-by-count":18,"title":["Associations of rare nicotinic cholinergic receptor gene variants to nicotine and alcohol dependence"],"prefix":"10.1002","volume":"171","author":[{"given":"Lingjun","family":"Zuo","sequence":"first","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Tan","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Research Center Beijing 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