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A genome-wide association study for stimulant dependence was performed in a discovery cohort of African- (AA) and European-ancestry (EA) subjects ascertained for genetic studies of alcohol, opioid, and cocaine use disorders. The sample comprised individuals with DSM-IV stimulant dependence (393 EA cases, 5288 EA controls; 155 AA cases, 5603 AA controls). An independent cohort from the family-based Collaborative Study on the Genetics of Alcoholism (532 EA cases, 7635 EA controls; 53 AA cases, AA 3352 controls) was used for replication. One variant in <jats:italic>SLC25A16<\/jats:italic> (rs2394476, <jats:italic>p<\/jats:italic>\u2009=\u20093.42\u2009\u00d7\u200910<jats:sup>\u221210<\/jats:sup>, odds ratio [OR]\u2009=\u20093.70) was GWS in AAs. Four other loci showed suggestive evidence, including <jats:italic>KCNA4<\/jats:italic> in AAs (rs11500237, <jats:italic>p<\/jats:italic>\u2009=\u20092.99\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>, OR\u2009=\u20092.31) which encodes one of the potassium voltage-gated channel protein that has been linked to several other substance use disorders, and <jats:italic>CPVL<\/jats:italic> in the combined population groups (rs1176440, <jats:italic>p<\/jats:italic>\u2009=\u20093.05\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>, OR\u2009=\u20091.35), whose expression was previously shown to be upregulated in the prefrontal cortex from users of cocaine, cannabis, and phencyclidine. Analysis of the top GWAS signals revealed a significant enrichment with nicotinic acetylcholine receptor genes (adjusted <jats:italic>p<\/jats:italic>\u2009=\u20090.04) and significant pleiotropy between stimulant dependence and alcohol dependence in EAs (<jats:italic>p<\/jats:italic><jats:sub><jats:italic>adj<\/jats:italic><\/jats:sub>\u2009=\u20093.6\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>), an anxiety disorder in EAs (<jats:italic>p<\/jats:italic><jats:sub><jats:italic>adj<\/jats:italic><\/jats:sub>\u2009=\u20092.1\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>), and ADHD in both AAs (<jats:italic>p<\/jats:italic><jats:sub><jats:italic>adj<\/jats:italic><\/jats:sub>\u2009=\u20093.0\u2009\u00d7\u200910<jats:sup>\u221233<\/jats:sup>) and EAs (<jats:italic>p<\/jats:italic><jats:sub><jats:italic>adj<\/jats:italic><\/jats:sub>\u2009=\u20096.7\u2009\u00d7\u200910<jats:sup>\u221235<\/jats:sup>). Our results implicate novel genes and pathways as having roles in the etiology of stimulant dependence.<\/jats:p>","DOI":"10.1038\/s41398-021-01440-5","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T09:03:03Z","timestamp":1625475783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genome-wide association study of stimulant dependence"],"prefix":"10.1038","volume":"11","author":[{"given":"Jiayi","family":"Cox","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Sherva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Wetherill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5549-2212","authenticated-orcid":false,"given":"Tatiana","family":"Foroud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0344-9690","authenticated-orcid":false,"given":"Howard J.","family":"Edenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-0450","authenticated-orcid":false,"given":"Henry R.","family":"Kranzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4067-1859","authenticated-orcid":false,"given":"Joel","family":"Gelernter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5533-4225","authenticated-orcid":false,"given":"Lindsay A.","family":"Farrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"1440_CR1","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1007\/7854_2011_187","volume":"12","author":"AB Hart","year":"2012","unstructured":"Hart, A. 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