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We aimed to discover potential loci by conducting a genome\u2010wide analysis of GAD symptoms in a large, population\u2010based sample of Hispanic\/Latino adults. Data came from 12,282 participants (aged 18\u201374) in the Hispanic Community Health Study\/Study of Latinos. Using a shortened Spielberger Trait Anxiety measure, we analyzed the following: (i) a GAD symptoms score restricted to the three items tapping diagnostic features of GAD as defined by DSM\u2010V; and (ii) a total trait anxiety score based on summing responses to all ten items. We first calculated the heritability due to common variants (h<jats:sup>2<\/jats:sup><jats:sub>SNP<\/jats:sub>) and then conducted a genome\u2010wide association study (GWAS) of GAD symptoms. Replication was attempted in three independent Hispanic cohorts (Multi\u2010Ethnic Study of Atherosclerosis, Women's Health Initiative, Army STARRS). The GAD symptoms score showed evidence of modest heritability (7.2%; <jats:italic>P<\/jats:italic>\u2009=\u20090.03), while the total trait anxiety score did not (4.97%; <jats:italic>P<\/jats:italic>\u2009=\u20090.20). One genotyped SNP (rs78602344) intronic to thrombospondin 2 (<jats:italic>THBS2<\/jats:italic>) was nominally associated (<jats:italic>P<\/jats:italic>\u2009=\u20095.28\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>) in the primary analysis adjusting for psychiatric medication use and significantly associated with the GAD symptoms score in the analysis excluding medication users (<jats:italic>P<\/jats:italic>\u2009=\u20094.18\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). However, meta\u2010analysis of the replication samples did not support this association. Although we identified a genome\u2010wide significant locus in this sample, we were unable to replicate this finding. Evidence for heritability was also only detected for GAD symptoms, and not the trait anxiety measure, suggesting differential genetic influences within the domain of trait anxiety. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32448","type":"journal-article","created":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T17:24:19Z","timestamp":1462814659000},"page":"132-143","source":"Crossref","is-referenced-by-count":49,"title":["Genome\u2010wide association study of generalized anxiety symptoms in the Hispanic Community Health Study\/Study of Latinos"],"prefix":"10.1002","volume":"174","author":[{"given":"Erin C.","family":"Dunn","sequence":"first","affiliation":[{"name":"Psychiatric and Neurodevelopmental Genetics Unit Massachusetts General Hospital Boston Massachusetts"},{"name":"Department of Psychiatry Harvard Medical School Boston Massachusetts"},{"name":"Stanley Center for Psychiatric Research The Broad Institute of Harvard and MIT Cambridge 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Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuqing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Institute for Translational Genomics and Population Sciences Los Angeles Biomedical Research Institute Harbor\u2010UCLA Medical Center Torrance California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Institute for Translational Genomics and Population Sciences Los Angeles Biomedical Research Institute Harbor\u2010UCLA Medical Center Torrance California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qibin","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome 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