title: Genetic risk variants for social anxiety.
abstract: Social anxiety is a neurobehavioral trait characterized by fear and reticence in social situations. Twin studies have shown that social anxiety has a heritable basis, shared with neuroticism and extraversion, but genetic studies have yet to demonstrate robust risk variants. We conducted genomewide association analysis (GWAS) of subjects within the Army Study To Assess Risk and Resilience in Servicemembers (Army STARRS) to (i) determine SNP-based heritability of social anxiety; (ii) discern genetic risk loci for social anxiety; and (iii) determine shared genetic risk with neuroticism and extraversion. GWAS were conducted within ancestral groups (EUR, AFR, LAT) using linear regression models for each of the three component studies in Army STARRS, and then meta-analyzed across studies. SNP-based heritability for social anxiety was significant (h2g= 0.12, P = 2.17 × 10-4in EUR). One meta-analytically genomewide significant locus was seen in each of EUR (rs708012, Chr 6: BP 36965970, P = 1.55 × 10-8; beta = 0.073) and AFR (rs78924501, Chr 1: BP 88406905, P = 3.58 × 10-8; beta = 0.265) samples. Social anxiety in Army STARRS was significantly genetically correlated (negatively) with extraversion (rg= -0.52, se = 0.22, P = 0.02) but not with neuroticism (rg= 0.05, se = 0.22, P = 0.81) or with an anxiety disorder factor score (rg= 0.02, se = 0.32, P = 0.94) from external GWAS meta-analyses. This first GWAS of social anxiety confirms a genetic basis for social anxiety, shared with extraversion but possibly less so with neuroticism. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, California.|Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.|VA San Diego Healthcare System, San Diego, California.
authors.forename: Murray B
authors.initials: MB
authors.lastname: Stein
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Jensen
authors.affiliation: Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Heeringa
authors.affiliation: Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Kessler
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, California.
authors.forename: Adam
authors.initials: A
authors.lastname: Maihofer
authors.affiliation: Department of Psychology, Harvard University, Cambridge, Massachusetts.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Nock
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ripke
authors.affiliation: Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, California.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Thomas
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ursano
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut.|Uniformed Services University of the Health Sciences, Bethesda, Maryland.|Department of Genetics, Yale University, New Haven, Connecticut.|Department of Neurobiology, Yale University, New Haven, Connecticut.
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000328:Adult; D001007:Anxiety / Q000235:genetics* / Q000523:psychology; D001008:Anxiety Disorders / Q000235:genetics; D005120:Extraversion, Psychological; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008889:Military Personnel / Q000523:psychology; D000075384:Neuroticism; D010551:Personality / Q000235:genetics; D010641:Phenotype; D000072861:Phobia, Social / Q000235:genetics* / Q000523:psychology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
keywords: anxiety; extraversion; neuroticism; social anxiety; social phobia