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We integrated SNP\u2010based, gene\u2010based, and protein\u2013protein interaction network analyses to identify shared risk genes or gene subnetworks for AD+ND in African Americans (AAs, <jats:italic>N<\/jats:italic>\u2009=\u20092,094) and European Americans (EAs, <jats:italic>N<\/jats:italic>\u2009=\u20091,207). The DSM\u2010IV criterion counts for AD and ND were modeled as two dependent variables in a multivariate linear mixed model, and analyzed separately for the two populations. The most significant SNP was rs6579845 in EAs (<jats:italic>p<\/jats:italic>\u2009&lt;\u20091.29\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>) in <jats:italic>GM2A<\/jats:italic>, which encodes GM2 ganglioside activator, and is a cis\u2010expression quantitative locus that affects <jats:italic>GM2A<\/jats:italic> expression in blood and brain tissues. However, this SNP was not replicated in our another small sample (<jats:italic>N<\/jats:italic>\u2009=\u2009678). We identified a subnetwork of 24 genes that contributed to the AD+ND criterion counts. In the gene\u2010set analysis for the subnetwork in an independent sample, the Study of Addiction: Genetics and Environment project (predominately EAs), these 24 genes as a set differed in AD+ND versus control subjects in EAs (<jats:italic>p<\/jats:italic>\u2009=\u2009.041). Functional enrichment analysis for this subnetwork revealed that the gene enrichment involved primarily nerve growth factor pathways, and cocaine and amphetamine addiction. In conclusion, we identified a genome\u2010wide significant variant at <jats:italic>GM2A<\/jats:italic> and a gene subnetwork underlying the genetic trait of shared AD+ND. These results increase our understanding of the shared (pleiotropic) genetic risk that underlies AD+ND.<\/jats:p>","DOI":"10.1002\/ajmg.b.32692","type":"journal-article","created":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T07:10:19Z","timestamp":1543475419000},"page":"3-11","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["GWAS and network analysis of co\u2010occurring nicotine and alcohol dependence identifies significantly associated alleles and network"],"prefix":"10.1002","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8341-2286","authenticated-orcid":false,"given":"Bo","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut"},{"name":"Department of Psychiatry Affiliated Hospital of Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-6946","authenticated-orcid":false,"given":"Bao\u2010Zhu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut"},{"name":"VA CT Healthcare Center  West Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7694-6391","authenticated-orcid":false,"given":"Hang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut"},{"name":"VA CT Healthcare Center  West Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-0450","authenticated-orcid":false,"given":"Henry","family":"Kranzler","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Center for Studies of Addiction, University of Pennsylvania and VISN 4 MIRECC, Crescenz VAMC  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4067-1859","authenticated-orcid":false,"given":"Joel","family":"Gelernter","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut"},{"name":"VA CT Healthcare Center  West Haven Connecticut"},{"name":"Department of Genetics Yale University School of Medicine  New Haven Connecticut"},{"name":"Department of Neuroscience Yale University School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,28]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association","year":"1994"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12569"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1198"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911109107"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl441"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2007.11.023"},{"key":"e_1_2_7_8_1","first-page":"115","article-title":"Lysosomal abnormalities in the pyramidal cells of the rat medial prefrontal cortex after chronic alcohol consumption and withdrawal","volume":"20","author":"Cadete\u2010Leite A.","year":"1988","journal-title":"Journal of Submicroscopic Cytology and Pathology"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10524"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09534"},{"key":"e_1_2_7_11_1","first-page":"214","article-title":"The collaborative study on the genetics of alcoholism: An update","volume":"26","author":"Edenberg H. 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