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However, systematic convergence and comparison evidence of genome\u2010wide findings is lacking for substance use. Here, we combined all the genome\u2010wide findings from both substance use behavior and disorder (SUBD) and identified common and distinguishing genetic factors for different SUBDs.<\/jats:p><\/jats:sec>Methods<\/jats:title>Systemic literature search for genome\u2010wide association (GWAS) and RNA\u2010seq studies of alcohol\/nicotine\/drug use behavior (partially meets or not reported diagnostic criteria) and alcohol use behavior and disorder (AUBD), nicotine use behavior and disorder (NUBD) and drug use behavior and disorder (DUBD) was performed using PubMed and the GWAS catalog. Drug use was focused upon cannabis, opioid, cocaine and methamphetamine use. GWAS studies required case\u2013control or case\/cohort samples. RNA\u2010seq studies were based on brain tissues. The genes which contained significant single nucleotide polymorphism (P<\/jats:italic>\u2009\u2264\u20091\u2009\u00d7\u200910\u22126<\/jats:sup>) in GWAS and reported as significant in RNA\u2010seq studies were extracted. Pathway enrichment was performed by using Metascape. Gene interaction networks were identified by using the Protein Interaction Network Analysis database.<\/jats:p><\/jats:sec>Results<\/jats:title>Total SUBD\u2010related 2910 genes were extracted from 75 GWAS studies (2\u2009773\u2009889 participants) and 17 RNA\u2010seq studies. By overlapping the genes and pathways of AUBD, NUBD and DUBD, four shared genes (CACNB2<\/jats:italic>, GRIN2B<\/jats:italic>, PLXDC2<\/jats:italic> and PKNOX2<\/jats:italic>), four shared pathways [two Gene Ontology (GO) terms of \u2018modulation of chemical synaptic transmission\u2019, \u2018regulation of trans\u2010synaptic signaling\u2019, two Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of \u2018dopaminergic synapse\u2019, \u2018cocaine addiction\u2019] were identified (significantly higher than random, P<\/jats:italic>\u00a0<\u20091\u00a0\u00d7\u00a010\u22125<\/jats:sup>). The top shared KEGG pathways (Benjamini\u2013Hochberg\u2010corrected P<\/jats:italic>\u2010value\u2009<\u00a00.05) in the pairwise comparison of AUBD versus DUBD, NUBD versus DUBD, AUBD versus NUBD were \u2018Epstein\u2013Barr virus infection\u2019, \u2018protein processing in endoplasmic reticulum\u2019 and \u2018neuroactive ligand\u2010receptor interaction\u2019, respectively. We also identified substance\u2010specific genetic factors: i.e. ADH1B<\/jats:italic> and ALDH2<\/jats:italic> were unique for AUBD, while CHRNA3<\/jats:italic> and CHRNA4<\/jats:italic> were unique for NUBD.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>This systematic review identifies the shared and unique genes and pathways for alcohol, nicotine and drug use behaviors and disorders at the genome\u2010wide level and highlights critical biological processes for the common and distinguishing vulnerability of substance use behaviors and disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/add.15908","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T07:53:28Z","timestamp":1651478008000},"page":"2515-2529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Common and distinguishing genetic factors for substance use behavior and disorder: an integrated analysis of genomic and transcriptomic studies from both human and animal studies"],"prefix":"10.1111","volume":"117","author":[{"given":"Xiang\u2010Wen","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences Peking University Health Science Center Beijing China"},{"name":"National Institute on Drug Dependence Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences Peking University Health Science Center Beijing China"},{"name":"National Institute on Drug Dependence Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Na","family":"Muhai","sequence":"additional","affiliation":[{"name":"Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang\u2010Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences Peking University Health Science Center Beijing China"},{"name":"National Institute on Drug Dependence Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences Peking University Health Science Center Beijing China"},{"name":"National Institute on Drug Dependence Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"National Institute on Drug Dependence Peking University Beijing China"},{"name":"Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Hua","family":"Chang","sequence":"additional","affiliation":[{"name":"Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6567-8160","authenticated-orcid":false,"given":"Jie","family":"Shi","sequence":"additional","affiliation":[{"name":"National Institute on Drug Dependence Peking University Beijing China"},{"name":"Beijing Key Laboratory of Drug Dependence Research Peking University Beijing 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