{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T11:27:25Z","timestamp":1768822045707,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AA021449"],"award-info":[{"award-number":["R01AA021449"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21DA045189"],"award-info":[{"award-number":["R21DA045189"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21DA044749"],"award-info":[{"award-number":["R21DA044749"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DA023248"],"award-info":[{"award-number":["R01DA023248"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AA023237"],"award-info":[{"award-number":["R21AA023237"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AA020319"],"award-info":[{"award-number":["R21AA020319"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AA021380"],"award-info":[{"award-number":["R21AA021380"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The gray matter volume (GMV) of the putamen has been reported to be regulated by kinectin 1 gene (<jats:italic>KTN1<\/jats:italic>). As a hub of the dopaminergic circuit, the putamen is widely implicated in the etiological processes of substance use disorders (SUD). Here, we aimed to identify robust and reliable associations between <jats:italic>KTN1<\/jats:italic> SNPs and SUD across multiple samples. We examined the associations between SUD and <jats:italic>KTN1<\/jats:italic> SNPs in four independent population\u2010based or family\u2010based samples (<jats:italic>n<\/jats:italic> = 10,209). The potential regulatory effects of the risk alleles on the putamen GMVs, the effects of alcohol, nicotine, marijuana and cocaine on <jats:italic>KTN1<\/jats:italic> mRNA expression, and the relationship between <jats:italic>KTN1<\/jats:italic> mRNA expression and SUD were explored. We found that a total of 23 SNPs were associated with SUD across at least two independent samples (1.4 \u00d7 10<jats:sup>\u22124<\/jats:sup> \u2264 <jats:italic>p<\/jats:italic> \u2264 0.049), including one SNP (rs12895072) across three samples (8.8 \u00d7 10<jats:sup>\u22123<\/jats:sup> \u2264 p \u2264 0.049). Four other SNPs were significantly or suggestively associated with SUD only in European\u2010Australians (4.8 \u00d7 10<jats:sup>\u22124<\/jats:sup> \u2264 <jats:italic>p<\/jats:italic> \u2264 0.058). All of the SUD\u2010risk alleles of these 27 SNPs increased (\u03b2 &gt; 0) the putamen GMVs and represented major alleles (<jats:italic>f<\/jats:italic> &gt; 0.5) in Europeans. Twenty\u2010two SNPs were potentially biologically functional. Alcohol, nicotine and cocaine significantly affected the <jats:italic>KTN1<\/jats:italic> mRNA expression, and the <jats:italic>KTN1<\/jats:italic> mRNA was differentially expressed between nicotine or cocaine dependent and control subjects. We concluded that there was a replicable and robust relationship among the <jats:italic>KTN1<\/jats:italic> variants, <jats:italic>KTN1<\/jats:italic> mRNA expression, putamen GMVs, molecular effects of substances, and SUD, suggesting that some risk <jats:italic>KTN1<\/jats:italic> alleles might increase kinectin 1 expression in the putamen, altering putamen structures and functions, and leading to SUD.<\/jats:p>","DOI":"10.1111\/adb.12888","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T04:56:06Z","timestamp":1583124966000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Significant, replicable, and functional associations between <i>KTN1<\/i> variants and alcohol and drug codependence"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-042X","authenticated-orcid":false,"given":"Xingguang","family":"Luo","sequence":"first","affiliation":[{"name":"Biological Psychiatry Research Center Beijing Huilongguan Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Shanghai Mental Health Center  Shanghai China"},{"name":"Department of Psychiatry Yale University School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingqun","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, College of Integrated Traditional Chinese and Western Medicine Fujian University of Traditional Chinese Medicine  Fuzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunlong","family":"Tan","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Research Center Beijing Huilongguan Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Research Center Beijing Huilongguan Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kebing","family":"Yang","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Research Center Beijing Huilongguan Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Xie","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Research Center Beijing Huilongguan Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Shi","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Research Center Beijing Huilongguan Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Tianjin Mental Health Center  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianying","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Zhuhai Municipal Maternal and Children's Health Hospital  Zhuhai Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingjun","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiang\u2010Shan R.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven CT USA"},{"name":"Department of Neuroscience Yale University School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.61.11.1107"},{"key":"e_1_2_7_3_1","unstructured":"Substance Abuse and Mental Health Services Administration (SAMHSA).Results from the 2013 National survey on drug use and health: summary of national findings. NSDUH Series H\u201048 HHS Publication No.(SMA) 14\u20134863. Rockville MD.2014."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl460"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10519-012-9529-y"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-200205000-00014"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-0812-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.140"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.108.053801"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(90)90042-P"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.10251"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.17040415"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.3.486"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214463"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2013.09.004"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3801"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30195"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14101"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2017.02.009"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15705-x"},{"key":"e_1_2_7_22_1","article-title":"Genetic architecture of subcortical brain structures in over 40,000 individuals worldwide","author":"Satizabal CL","year":"2017","journal-title":"bioRxiv"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3043"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3955"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2011.00540.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163668"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.36"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000008195"},{"issue":"1","key":"e_1_2_7_29_1","article-title":"Putamen gray matter volumes in neuropsychiatric and neurodegenerative disorders","volume":"3","author":"Luo X","year":"2019","journal-title":"World J Psychiatry Ment Health Res"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1086\/504113"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180356"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.15288\/jsa.1994.55.149"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.145"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2005.04.005"},{"key":"e_1_2_7_35_1","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"American Psychiatric Association","year":"1994"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000529"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.229"},{"key":"e_1_2_7_38_1","doi-asserted-by":"crossref","unstructured":"XuZ TaylorJA.SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies.Nucleic acids research.2009;37(Web Server issue):W600\u2013605.","DOI":"10.1093\/nar\/gkp290"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq330"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163812"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8794-6-26"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-606"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-5-r48"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30512"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.70"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-10-1299"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.01.003"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(96)12752-X"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2013.00152"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.58"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fadb.12888","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.12888","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/adb.12888","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.12888","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T14:12:48Z","timestamp":1693663968000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.12888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1111\/adb.12888"],"URL":"https:\/\/doi.org\/10.1111\/adb.12888","archive":["Portico"],"relation":{},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3]]},"assertion":[{"value":"2019-11-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12888"}}