title: Genome-wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos.
abstract: Although generalized anxiety disorder (GAD) is heritable and aggregates in families, no genomic loci associated with GAD have been reported. We aimed to discover potential loci by conducting a genome-wide analysis of GAD symptoms in a large, population-based sample of Hispanic/Latino adults. Data came from 12,282 participants (aged 18-74) 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-V; and (ii) a total trait anxiety score based on summing responses to all ten items. We first calculated the heritability due to common variants (h2SNP) and then conducted a genome-wide association study (GWAS) of GAD symptoms. Replication was attempted in three independent Hispanic cohorts (Multi-Ethnic Study of Atherosclerosis, Women's Health Initiative, Army STARRS). The GAD symptoms score showed evidence of modest heritability (7.2%; P = 0.03), while the total trait anxiety score did not (4.97%; P = 0.20). One genotyped SNP (rs78602344) intronic to thrombospondin 2 (THBS2) was nominally associated (P = 5.28 × 10-8) in the primary analysis adjusting for psychiatric medication use and significantly associated with the GAD symptoms score in the analysis excluding medication users (P = 4.18 × 10-8). However, meta-analysis of the replication samples did not support this association. Although we identified a genome-wide 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. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.|Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Dunn
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Tamar
authors.initials: T
authors.lastname: Sofer
authors.affiliation: Department of Psychology, San Diego State University, La Jolla, California.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Gallo
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Gogarten
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.|Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts.|Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, California.
authors.forename: Murray B
authors.initials: MB
authors.lastname: Stein
authors.affiliation: Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ursano
authors.affiliation: Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.|Department of Medicine, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: School of Public Health, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Maria
authors.initials: M
authors.lastname: Argos
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Medical Social Sciences, Northwestern University, Chicago, Illinois.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Penedo
authors.affiliation: College and Arts and Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Krista
authors.initials: K
authors.lastname: Perreira
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wassertheil-Smoller
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.|Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
mesh_terms: D000328:Adult; D000368:Aged; D001007:Anxiety / Q000235:genetics* / Q000523:psychology; D001008:Anxiety Disorders / Q000235:genetics* / Q000523:psychology; D005006:Ethnicity / Q000235:genetics / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
keywords: Hispanics/Latinos; anxiety; genetic association study