{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:44:03Z","timestamp":1776919443383,"version":"3.51.2"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T00:00:00Z","timestamp":1549238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T00:00:00Z","timestamp":1549238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000027","name":"U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA010201"],"award-info":[{"award-number":["AA010201"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA025095"],"award-info":[{"award-number":["AA025095"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA030976"],"award-info":[{"award-number":["DA030976"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA030976"],"award-info":[{"award-number":["DA030976"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA030976"],"award-info":[{"award-number":["DA030976"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A limited number of genetic variants have been identified in traditional GWAS as risk or protective factors for alcohol use disorders (AUD) and related phenotypes. We herein report whole-genome association and rare-variant analyses on AUD traits in American Indians (AI) and European Americans (EA). We evaluated 742 AIs and 1711 EAs using low-coverage whole-genome sequencing. Phenotypes included: (1) a metric based on the occurrence of 36 alcohol-related life events that reflect AUD severity; (2) two alcohol-induced affective symptoms that accompany severe AUDs. We identified two new loci for alcohol-related life events with converging evidence from both cohorts: rare variants of K<jats:sub>2P<\/jats:sub>channel gene<jats:italic>KCNK2<\/jats:italic>, and rare missense and splice-site variants in pro-inflammatory mediator gene<jats:italic>PDE4C<\/jats:italic>. A<jats:italic>NAF1-FSTL5<\/jats:italic>intergenic variant and an<jats:italic>FSTL5<\/jats:italic>variant were respectively associated with alcohol-related life events in AI and EA.<jats:italic>PRKG2<\/jats:italic>of serine\/threonine protein kinase family, and rare variants in interleukin subunit gene<jats:italic>EBI3<\/jats:italic>(<jats:italic>IL-27B<\/jats:italic>) were uniquely associated with alcohol-induced affective symptoms in AI. LncRNA<jats:italic>LINC02347<\/jats:italic>on 12q24.32 was uniquely associated with alcohol-induced depression in EA. The top GWAS findings were primarily rare\/low-frequency variants in AI, and common variants in EA. Adrenal gland was the most enriched in tissue-specific gene expression analysis for alcohol-related life events, and nucleus accumbens was the most enriched for alcohol-induced affective states in AI. Prefrontal cortex was the most enriched in EA for both traits. These studies suggest that whole-genome sequencing can identify novel, especially uncommon, variants associated with severe AUD phenotypes although the findings may be population specific.<\/jats:p>","DOI":"10.1038\/s41398-019-0397-6","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T15:03:28Z","timestamp":1549292608000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Genetic loci for alcohol-related life events and substance-induced affective symptoms: indexing the \u201cdark side\u201d of addiction"],"prefix":"10.1038","volume":"9","author":[{"given":"Qian","family":"Peng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Bizon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian R.","family":"Gizer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirk C.","family":"Wilhelmsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy L.","family":"Ehlers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,2,4]]},"reference":[{"key":"397_CR1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1001\/jamapsychiatry.2015.0584","volume":"72","author":"BF Grant","year":"2015","unstructured":"Grant, B. F. et al. Epidemiology of DSM-5 alcohol use disorder: Results from the national epidemiologic survey on alcohol and related conditions III. JAMA Psychiatry 72, 757\u2013766 (2015).","journal-title":"JAMA Psychiatry"},{"key":"397_CR2","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/nrgastro.2013.86","volume":"10","author":"HJ Edenberg","year":"2013","unstructured":"Edenberg, H. J. & Foroud, T. Genetics and alcoholism. Nat. Rev. Gastroenterol. Hepatol. 10, 487\u2013494 (2013).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"397_CR3","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1111\/acer.12792","volume":"39","author":"AB Hart","year":"2015","unstructured":"Hart, A. B. & Kranzler, H. R. Alcohol dependence genetics: Lessons learned from genome-wide association studies (GWAS) and post-GWAS analyses. Alcohol.: Clin. Exp. Res. 39, 1312\u20131327 (2015).","journal-title":"Alcohol.: Clin. Exp. Res."},{"key":"397_CR4","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/mp.2013.145","volume":"19","author":"J Gelernter","year":"2014","unstructured":"Gelernter, J. et al. Genome-wide association study of alcohol dependence:significant findings in African- and European-Americans including novel risk loci. Mol. Psychiatry 19, 41\u201349 (2014).","journal-title":"Mol. Psychiatry"},{"key":"397_CR5","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1038\/mp.2017.101","volume":"22","author":"E Jorgenson","year":"2017","unstructured":"Jorgenson, E. et al. Genetic contributors to variation in alcohol consumption vary by race\/ethnicity in a large multi-ethnic genome-wide association study. Mol. Psychiatry 22, 1359 (2017).","journal-title":"Mol. Psychiatry"},{"key":"397_CR6","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1002\/ajmg.b.30346","volume":"141B","author":"C Johnson","year":"2006","unstructured":"Johnson, C. et al. Pooled association genome scanning for alcohol dependence using 104,268 SNPs: Validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism. Am. J. Med. Genet. Part B: Neuropsychiatr. Genet. 141B, 844\u2013853 (2006).","journal-title":"Am. J. Med. Genet. Part B: Neuropsychiatr. Genet."},{"key":"397_CR7","doi-asserted-by":"publisher","first-page":"7119","DOI":"10.1073\/pnas.1017288108","volume":"108","author":"G Schumann","year":"2011","unstructured":"Schumann, G. et al. Genome-wide association andgenetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proc. Natl Acad. Sci. 108, 7119\u20137124 (2011).","journal-title":"Proc. Natl Acad. Sci."},{"key":"397_CR8","doi-asserted-by":"publisher","first-page":"809","DOI":"10.3945\/ajcn.110.001776","volume":"93","author":"I Baik","year":"2011","unstructured":"Baik, I., Cho, N. H., Kim, S. H., Han, B. -G. & Shin, C. Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men. Am. J. Clin. Nutr. 93, 809\u2013816 (2011).","journal-title":"Am. J. Clin. Nutr."},{"key":"397_CR9","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1038\/mp.2012.143","volume":"18","author":"JC Wang","year":"2012","unstructured":"Wang, J. C. et al. A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. Mol. Psychiatry 18, 1218 (2012).","journal-title":"Mol. Psychiatry"},{"key":"397_CR10","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1001\/archgenpsychiatry.2009.83","volume":"66","author":"J Treutlein","year":"2009","unstructured":"Treutlein, J. et al. Genome-wide association study of alcohol dependence. Arch. Gen. Psychiatry 66, 773\u2013784 (2009).","journal-title":"Arch. Gen. Psychiatry"},{"key":"397_CR11","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1038\/mp.2017.153","volume":"22","author":"TK Clarke","year":"2017","unstructured":"Clarke, T. K. et al. Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112\u2009117). Mol. Psychiatry 22, 1376 (2017).","journal-title":"Mol. Psychiatry"},{"key":"397_CR12","doi-asserted-by":"publisher","first-page":"14372","DOI":"10.1073\/pnas.1611243113","volume":"113","author":"G Schumann","year":"2016","unstructured":"Schumann, G. et al. KLB is associated with alcohol drinking, and its gene product \u03b2-Klotho is necessary for FGF21 regulation of alcohol preference. Proc. Natl Acad. Sci. 113, 14372 (2016).","journal-title":"Proc. Natl Acad. Sci."},{"key":"397_CR13","doi-asserted-by":"crossref","unstructured":"Sanchez-Roige, S. et al. Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,958). bioRxiv 2018.","DOI":"10.1101\/275917"},{"key":"397_CR14","unstructured":"Compton, W. M., Thomas, Y. F., Stinson, F. S. & Grant, B. F. Prevalence, correlates, disability, and comorbidity of DSM-IV drug abuse and dependence in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch. Gen. Psychiatry"},{"key":"397_CR15","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1176\/appi.ajp.2012.12010113","volume":"170","author":"CL Ehlers","year":"2013","unstructured":"Ehlers, C. L. & Gizer, I. R. Evidence for a genetic component for substance dependence in Native Americans. Am. J. Psychiatry 170, 154\u2013164 (2013).","journal-title":"Am. J. Psychiatry"},{"key":"397_CR16","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1097\/01.ALC.0000141821.06062.20","volume":"28","author":"CL Ehlers","year":"2004","unstructured":"Ehlers, C. L., Spence, J. P., Wall, T. L., Gilder, D. A. & Carr, L. G. Association of ALDH1 promoter polymorphisms with alcohol-related phenotypes in southwest California Indians. Alcohol. Clin. Exp. Res. 28, 1481\u20131486 (2004).","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"397_CR17","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1002\/ajmg.b.32272","volume":"165","author":"Q Peng","year":"2014","unstructured":"Peng, Q. et al. Association and ancestry analysis of sequence variants in ADH and ALDH using alcohol-related phenotypes in a Native American community sample. Am. J. Med. Genet. Part B: Neuropsychiatr. Genet. 165, 673\u2013683 (2014).","journal-title":"Am. J. Med. Genet. Part B: Neuropsychiatr. Genet."},{"key":"397_CR18","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1111\/acer.13480","volume":"41","author":"Q Peng","year":"2017","unstructured":"Peng, Q., Gizer, I. R., Wilhelmsen, K. C. & Ehlers, C. L. Associations between genomic variants in alcohol dehydrogenase genes and alcohol symptomatology in American Indians and European Americans: Distinctions and convergence. Alcohol.: Clin. Exp. Res. 41, 1695\u20131704 (2017).","journal-title":"Alcohol.: Clin. Exp. Res."},{"key":"397_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15288\/QJSA.1946.7.1","volume":"7","author":"EM Jellinek","year":"1946","unstructured":"Jellinek, E. M. Phases in the drinking history of alcoholics. Q. J. Stud. Alcohol 7, 1\u201388 (1946). 0033-5649 (Print).","journal-title":"Q. J. Stud. Alcohol"},{"key":"397_CR20","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1176\/ajp.150.5.786","volume":"150","author":"MA Schuckit","year":"1993","unstructured":"Schuckit, M. A., Smith, T. L., Anthenelli, R. & Irwin, M. Clinical course of alcoholism in 636 male inpatients. Am. J. Psychiatry 150, 786\u2013792 (1993).","journal-title":"Am. J. Psychiatry"},{"key":"397_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/10550490252801594","volume":"11","author":"MA Schuckit","year":"2002","unstructured":"Schuckit, M. A. et al. Similarities in the clinical characteristics related to alcohol dependence in two populations. Am. J. Addict. 11, 1\u20139 (2002).","journal-title":"Am. J. Addict."},{"key":"397_CR22","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1111\/j.1521-0391.2009.00021.x","volume":"19","author":"CL Ehlers","year":"2010","unstructured":"Ehlers, C. L. et al. Age at regular drinking, clinical course, and heritability of alcohol dependence in the San Francisco Family Study: A gender analysis. Am. J. Addict. 19, 101\u2013110 (2010).","journal-title":"Am. J. Addict."},{"key":"397_CR23","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1111\/ajad.12290","volume":"24","author":"CL Ehlers","year":"2015","unstructured":"Ehlers, C. L., Stouffer, G. M., Corey, L. & Gilder, D. A. The clinical course of DSM-5 alcohol use disorders in young adult native and Mexican Americans. Am. J. Addict. 24, 713\u2013721 (2015).","journal-title":"Am. J. Addict."},{"key":"397_CR24","doi-asserted-by":"publisher","first-page":"218","DOI":"10.15288\/jsa.1995.56.218","volume":"56","author":"MA Schuckit","year":"1995","unstructured":"Schuckit, M. A., Anthenelli, R. M., Bucholz, K. K., Hesselbrock, V. M. & Tipp, J. The time course of development of alcohol-related problems in men and women. J. Stud. Alcohol. 56, 218\u2013225 (1995).","journal-title":"J. Stud. Alcohol."},{"key":"397_CR25","doi-asserted-by":"publisher","first-page":"158","DOI":"10.15288\/jsa.2001.62.158","volume":"62","author":"KL Venner","year":"2001","unstructured":"Venner, K. L. & Miller, W. R. Progression of alcohol problems in a Navajo sample. J. Stud. Alcohol. 62, 158\u2013165 (2001).","journal-title":"J. Stud. Alcohol."},{"key":"397_CR26","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1176\/appi.ajp.161.7.1204","volume":"161","author":"CL Ehlers","year":"2004","unstructured":"Ehlers, C. L., Wall, T. L., Betancourt, M. & Gilder, D. A. The clinical course of alcoholism in 243 Mission Indians. Am. J. Psychiatry 161, 1204\u20131210 (2004).","journal-title":"Am. J. Psychiatry"},{"key":"397_CR27","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1080\/10826080500391803","volume":"41","author":"BP Malcolm","year":"2006","unstructured":"Malcolm, B. P., Hesselbrock, M. N. & Segal, B. Multiple substance dependence and course of alcoholism among Alaska Native men and women. Subst. Use Misuse 41, 729\u2013741 (2006).","journal-title":"Subst. Use Misuse"},{"key":"397_CR28","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1080\/10550880802324754","volume":"27","author":"DM Scott","year":"2008","unstructured":"Scott, D. M. et al. Clinical course of alcohol dependence in African Americans. J. Addict. Dis. 27, 43\u201350 (2008).","journal-title":"J. Addict. Dis."},{"key":"397_CR29","doi-asserted-by":"publisher","first-page":"834","DOI":"10.15288\/jsad.2008.69.834","volume":"69","author":"LK Montane-Jaime","year":"2008","unstructured":"Montane-Jaime, L. K. et al. The clinical course of alcoholism in Trinidad and Tobago. J. Stud. Alcohol. Drugs 69, 834\u2013839 (2008).","journal-title":"J. Stud. Alcohol. Drugs"},{"key":"397_CR30","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1176\/ajp.154.7.948","volume":"154","author":"MA Schuckit","year":"1997","unstructured":"Schuckit, M. A. Comparison of induced and independent major depressive disorders in 2,945 alcoholics. Am. J. Psychiatry 154, 948\u2013957 (1997).","journal-title":"Am. J. Psychiatry"},{"key":"397_CR31","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/j.1360-0443.2006.01592.x","volume":"101","author":"MA Schuckit","year":"2006","unstructured":"Schuckit, M. A. Comorbidity between substance use disorders and psychiatric conditions. Addiction 101, 76\u201388 (2006).","journal-title":"Addiction"},{"key":"397_CR32","doi-asserted-by":"crossref","unstructured":"Ehlers, C. L., Gilder, D. A., Gizer I. R. & Wilhelmsen K. C. Indexing the \u2018dark side of addiction': substance-induced affective symptoms and alcohol use disorders. Addiction 114, 139\u2013149 (2019).","DOI":"10.1111\/add.14431"},{"key":"397_CR33","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1038\/nn1105-1442","volume":"8","author":"GF Koob","year":"2005","unstructured":"Koob, G. F. & Le Moal, M. Plasticity of reward neurocircuitry and the \u2018dark side' of drug addiction. Nat. Neurosci. 8, 1442 (2005).","journal-title":"Nat. Neurosci."},{"key":"397_CR34","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1097\/01.ALC.0000057122.36127.C2","volume":"27","author":"GF Koob","year":"2003","unstructured":"Koob, G. F. Alcoholism: Allostasis and beyond. Alcohol.: Clin. Exp. Res. 27, 232\u2013243 (2003).","journal-title":"Alcohol.: Clin. Exp. Res."},{"key":"397_CR35","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/S2215-0366(16)00104-8","volume":"3","author":"GF Koob","year":"2016","unstructured":"Koob, G. F. & Volkow, N. D. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry 3, 760\u2013773 (2016).","journal-title":"Lancet Psychiatry"},{"key":"397_CR36","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/nrg2554","volume":"10","author":"KA Frazer","year":"2009","unstructured":"Frazer, K. A., Murray, S. S., Schork, N. J. & Topol, E. J. Human genetic variation and its contribution to complex traits. Nat. Rev. Genet. 10, 241\u2013251 (2009).","journal-title":"Nat. Rev. Genet."},{"key":"397_CR37","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1038\/ng.3390","volume":"47","author":"J Yang","year":"2015","unstructured":"Yang, J. et al. Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index. Nat. Genet. 47, 1114 (2015).","journal-title":"Nat. Genet."},{"key":"397_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-85","volume":"15","author":"C Bizon","year":"2014","unstructured":"Bizon, C. et al. Variant calling in low-coverage whole genome sequencing of a Native American population sample. BMC Genom. 15, 85 (2014).","journal-title":"BMC Genom."},{"key":"397_CR39","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1097\/01.ALC.0000107200.88229.57","volume":"28","author":"KL Seaton","year":"2004","unstructured":"Seaton, K. L., Cornell, J. L., Wilhelmsen, K. C. & Vieten, C. Effective strategies for recruiting families ascertained through alcoholic probands. Alcohol. Clin. Exp. Res. 28, 78\u201384 (2004).","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"397_CR40","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1097\/01.ALC.0000142261.32980.64","volume":"28","author":"C Vieten","year":"2004","unstructured":"Vieten, C., Seaton, K. L., Feiler, H. S. & Wilhelmsen, K. C. The University of California, San Francisco Family Alcoholism Study. I. Design, methods, and demographics. Alcohol.: Clin. Exp. Res. 28, 1509\u20131516 (2004).","journal-title":"Alcohol.: Clin. Exp. Res."},{"key":"397_CR41","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.drugalcdep.2010.07.017","volume":"113","author":"IR Gizer","year":"2011","unstructured":"Gizer, I. R. et al. Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study. Drug Alcohol. Depend. 113, 125\u2013132 (2011).","journal-title":"Drug Alcohol. Depend."},{"key":"397_CR42","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1002\/ajmg.b.31218","volume":"156B","author":"CL Ehlers","year":"2011","unstructured":"Ehlers, C. L., Gizer, I. R., Gilder, D. A. & Wilhelmsen, K. C. Linkage analyses of stimulant dependence, craving, and heavy use in American Indians. Am. J. Med. Genet. Part B: Neuropsychiatr. Genet. 156B, 772\u2013780 (2011).","journal-title":"Am. J. Med. Genet. Part B: Neuropsychiatr. Genet."},{"key":"397_CR43","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/ng.548","volume":"42","author":"HM Kang","year":"2010","unstructured":"Kang, H. M. et al. Variance component model to account for sample structure in genome-wide association studies. Nat. Genet. 42, 348\u2013354 (2010).","journal-title":"Nat. Genet."},{"key":"397_CR44","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/ajhb.22521","volume":"26","author":"TM Norden-Krichmar","year":"2014","unstructured":"Norden-Krichmar, T. M. et al. Correlation analysis of genetic admixture and social identification with body mass index in a Native American community. Am. J. Hum. Biol. 26, 347\u2013360 (2014).","journal-title":"Am. J. Hum. Biol."},{"key":"397_CR45","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1086\/383251","volume":"74","author":"DR Nyholt","year":"2004","unstructured":"Nyholt, D. R. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am. J. Human. Genet. 74, 765\u2013769 (2004).","journal-title":"Am. J. Human. Genet."},{"key":"397_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/srep32894","volume":"6","author":"A Bakshi","year":"2016","unstructured":"Bakshi, A. et al. Fast set-based association analysis using summary data from GWAS identifies novel gene loci for human complex traits. Sci. Rep. 6, 32894 (2016).","journal-title":"Sci. Rep."},{"key":"397_CR47","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.ajhg.2008.06.024","volume":"83","author":"B Li","year":"2008","unstructured":"Li, B. & Leal, S. M. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am. J. Human. Genet. 83, 311\u2013321 (2008).","journal-title":"Am. J. Human. Genet."},{"key":"397_CR48","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/nn.3801","volume":"17","author":"A Ramasamy","year":"2014","unstructured":"Ramasamy, A. et al. Genetic variability in the regulation of gene expression in ten regions of the human brain. Nat. Neurosci. 17, 1418\u20131428 (2014).","journal-title":"Nat. Neurosci."},{"key":"397_CR49","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","volume":"7","author":"IA Adzhubei","year":"2010","unstructured":"Adzhubei, I. A. et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248\u2013249 (2010).","journal-title":"Nat. Methods"},{"key":"397_CR50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116815","volume":"10","author":"PH Pham","year":"2015","unstructured":"Pham, P. H., Shipman, W. J., Erikson, G. A., Schork, N. J. & Torkamani, A. Scripps genome ADVISER: Annotation and distributed variant interpretation SERver. PLoS ONE 10, e0116815 (2015).","journal-title":"PLoS ONE"},{"issue":"suppl 2","key":"397_CR51","doi-asserted-by":"publisher","first-page":"W214","DOI":"10.1093\/nar\/gkq537","volume":"38","author":"D Warde-Farley","year":"2010","unstructured":"Warde-Farley, D. et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucl. Acids Res. 38(suppl 2), W214\u2013W220 (2010).","journal-title":"Nucl. Acids Res."},{"key":"397_CR52","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"DW Huang","year":"2008","unstructured":"Huang, D. W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44 (2008).","journal-title":"Nat. Protoc."},{"key":"397_CR53","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nrn2117","volume":"8","author":"E Honore","year":"2007","unstructured":"Honore, E. The neuronal background K2P channels: focus on TREK1. Nat. Rev. Neurosci. 8, 251\u2013261 (2007).","journal-title":"Nat. Rev. Neurosci."},{"key":"397_CR54","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1038\/nn1749","volume":"9","author":"C Heurteaux","year":"2006","unstructured":"Heurteaux, C. et al. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nat. Neurosci. 9, 1134 (2006).","journal-title":"Nat. Neurosci."},{"key":"397_CR55","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1097\/FPC.0b013e32832cbe61","volume":"19","author":"YJ Liou","year":"2009","unstructured":"Liou, Y. J. et al. Support for the involvement of the KCNK2 gene in major depressive disorder and response to antidepressant treatment. Pharm. Genom. 19, 735\u2013741 (2009).","journal-title":"Pharm. Genom."},{"key":"397_CR56","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1111\/j.1601-183X.2012.00803.x","volume":"11","author":"SJ Kang","year":"2012","unstructured":"Kang, S. J. et al. Family-based genome-wide association study of frontal \u03b8 oscillations identifies potassium channel gene KCNJ6. Genes Brain. Behav. 11, 712\u2013719 (2012).","journal-title":"Genes Brain. Behav."},{"key":"397_CR57","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1210\/er.2013-1053","volume":"35","author":"MF Azevedo","year":"2014","unstructured":"Azevedo, M. F. et al. Clinical and molecular genetics of the phosphodiesterases (PDEs). Endocr. Rev. 35, 195\u2013233 (2014).","journal-title":"Endocr. Rev."},{"key":"397_CR58","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1111\/j.1530-0277.2012.01845.x","volume":"36","author":"RT Wen","year":"2012","unstructured":"Wen, R. -T. et al. The phosphodiesterase-4 (PDE4) inhibitor rolipram decreases ethanol seeking and consumption in alcohol-preferring fawn-hooded rats. Alcohol.: Clin. Exp. Res. 36, 2157\u20132167 (2012).","journal-title":"Alcohol.: Clin. Exp. Res."},{"key":"397_CR59","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.alcohol.2015.03.007","volume":"49","author":"ML Logrip","year":"2015","unstructured":"Logrip, M. L. Phosphodiesterase regulation of alcohol drinking in rodents. Alcohol (Fayettev., NY) 49, 795\u2013802 (2015).","journal-title":"Alcohol (Fayettev., NY)"},{"key":"397_CR60","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3389\/fnins.2014.00129","volume":"8","author":"YA Blednov","year":"2014","unstructured":"Blednov, Y. A., Benavidez, J. M., Black, M. & Harris, R. A. Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL\/6J mice. Front. Neurosci. 8, 129 (2014).","journal-title":"Front. Neurosci."},{"key":"397_CR61","doi-asserted-by":"crossref","unstructured":"Harris, R. A. & Blednov Y. A. Neuroimmune Genes and Alcohol Drinking Behavior. (eds Cui, C., Grandison, L. & Noronha, A.), Neural-Immune Interactions in Brain Function and Alcohol Related Disorders, 425\u2013440 (Springer US, Boston, MA) (2013).","DOI":"10.1007\/978-1-4614-4729-0_13"},{"key":"397_CR62","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.conb.2013.01.024","volume":"23","author":"J Mayfield","year":"2013","unstructured":"Mayfield, J., Ferguson, L. & Harris, R. A. Neuroimmune signaling: a key component of alcohol abuse. Curr. Opin. Neurobiol. 23, 513\u2013520 (2013).","journal-title":"Curr. Opin. Neurobiol."},{"issue":"D1","key":"397_CR63","doi-asserted-by":"publisher","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","volume":"44","author":"M Kanehisa","year":"2016","unstructured":"Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M. & Tanabe, M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44(D1), D457\u2013D462 (2016).","journal-title":"Nucleic Acids Res."},{"key":"397_CR64","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s10519-013-9606-x","volume":"43","author":"M McGue","year":"2013","unstructured":"McGue, M. et al. A genome-wide association study of behavioral disinhibition. Behav. Genet. 43, 363\u2013373 (2013).","journal-title":"Behav. Genet."},{"key":"397_CR65","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042646","volume":"7","author":"AB Hart","year":"2012","unstructured":"Hart, A. B. et al. Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13). PLoS. One. 7, e42646 (2012).","journal-title":"PLoS. One."},{"key":"397_CR66","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ajhg.2016.11.007","volume":"100","author":"AV Ahola-Olli","year":"2016","unstructured":"Ahola-Olli, A. V. et al. Genome-wide association study identifies 27 loci influencing concentrations of circulating cytokines and growth factors. Am. J. Human Genet. 100, 40\u201350 (2016).","journal-title":"Am. J. Human Genet."},{"key":"397_CR67","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1097\/FPC.0000000000000250","volume":"27","author":"Q Li","year":"2017","unstructured":"Li, Q. et al. Genome-wide association study of paliperidone efficacy. Pharm. Genom. 27, 7\u201318 (2017).","journal-title":"Pharm. Genom."},{"key":"397_CR68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006528","volume":"13","author":"M Graff","year":"2017","unstructured":"Graff, M. et al. Genome-wide physical activity interactions in adiposity\u2014A meta-analysis of 200,452 adults. PLoS Genet. 13, e1006528 (2017).","journal-title":"PLoS Genet."},{"key":"397_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14977","volume":"8","author":"AE Justice","year":"2017","unstructured":"Justice, A. E. et al. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat. Commun. 8, 14977 (2017).","journal-title":"Nat. Commun."},{"key":"397_CR70","doi-asserted-by":"crossref","unstructured":"Smit, D. J. A., et al. Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity. bioRxiv (2017.","DOI":"10.1101\/232330"},{"key":"397_CR71","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1080\/15476286.2016.1207036","volume":"13","author":"WL Ng","year":"2016","unstructured":"Ng, W. L. et al. Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4\/LPS pathway. RNA Biol. 13, 861\u2013871 (2016).","journal-title":"RNA Biol."},{"key":"397_CR72","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1176\/appi.ajp.2012.12020237","volume":"170","author":"R Uher","year":"2013","unstructured":"Uher, R. et al. Common genetic variation and antidepressant efficacy in major depressive disorder: A meta-analysis of three genome-wide pharmacogenetic studies. Am. J. Psychiatry 170, 207\u2013217 (2013).","journal-title":"Am. J. Psychiatry"},{"key":"397_CR73","doi-asserted-by":"publisher","first-page":"6644","DOI":"10.1074\/jbc.M116.762021","volume":"292","author":"S Chehboun","year":"2017","unstructured":"Chehboun, S. et al. Epstein-Barr virus-induced gene 3 (EBI3) can mediate IL-6 trans-signaling. J. Biol. Chem. 292, 6644\u20136656 (2017).","journal-title":"J. Biol. Chem."},{"key":"397_CR74","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-4-r56","volume":"15","author":"MN Davies","year":"2014","unstructured":"Davies, M. N. et al. Hypermethylation in the ZBTB20 gene is associated with major depressive disorder. Genome Biol. 15, R56 (2014).","journal-title":"Genome Biol."},{"key":"397_CR75","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1755-8166-4-9","volume":"4","author":"J Al-Zahrani","year":"2011","unstructured":"Al-Zahrani, J. et al. Chromosome 12q24.31-q24.33 deletion causes multiple dysmorphic features and developmental delay: First mosaic patient and overview of the phenotype related to 12q24qter defects. Mol. Cytogenet. 4, 9 (2011).","journal-title":"Mol. Cytogenet."},{"key":"397_CR76","doi-asserted-by":"publisher","first-page":"10531","DOI":"10.1074\/jbc.M212083200","volume":"278","author":"K Oh-hashi","year":"2003","unstructured":"Oh-hashi, K., Naruse, Y., Amaya, F., Shimosato, G. & Tanaka, M. Cloning and characterization of a novel GRP78-binding protein in the rat brain. J. Biol. Chem. 278, 10531\u201310537 (2003).","journal-title":"J. Biol. Chem."},{"key":"397_CR77","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.85","volume":"2","author":"A Erhardt","year":"2012","unstructured":"Erhardt, A. et al. Replication and meta-analysis of TMEM132D gene variants in panic disorder. Transl. Psychiatry 2, e156 (2012).","journal-title":"Transl. Psychiatry"},{"key":"397_CR78","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/sj.mp.4002151","volume":"13","author":"P Sklar","year":"2008","unstructured":"Sklar, P. et al. Whole-genome association study of bipolar disorder. Mol. Psychiatry 13, 558 (2008).","journal-title":"Mol. Psychiatry"},{"key":"397_CR79","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/ng.3749","volume":"49","author":"JM Lane","year":"2016","unstructured":"Lane, J. M. et al. Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits. Nat. Genet. 49, 274 (2016).","journal-title":"Nat. Genet."},{"key":"397_CR80","doi-asserted-by":"publisher","first-page":"4510","DOI":"10.1210\/jc.2005-0035","volume":"90","author":"EO Bixler","year":"2005","unstructured":"Bixler, E. O. et al. Excessive daytime sleepiness in a general population sample: The role of sleep apnea, age, obesity, diabetes, and depression. J. Clin. Endocrinol. Metab. 90, 4510\u20134515 (2005).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"397_CR81","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nature09165","volume":"466","author":"AK Maunakea","year":"2010","unstructured":"Maunakea, A. K. et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 466, 253 (2010).","journal-title":"Nature"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-019-0397-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-019-0397-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-019-0397-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T14:43:16Z","timestamp":1720968196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-019-0397-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,4]]},"references-count":81,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["397"],"URL":"https:\/\/doi.org\/10.1038\/s41398-019-0397-6","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,4]]},"assertion":[{"value":"3 August 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"71"}}