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Meta-Analysis
. 2017 Mar;174(2):120-131.
doi: 10.1002/ajmg.b.32520.

Genetic risk variants for social anxiety

Murray B Stein  1   2   3 , Chia-Yen Chen  4   5 , Sonia Jain  2 , Kevin P Jensen  6   7 , Feng He  2 , Steven G Heeringa  8 , Ronald C Kessler  9 , Adam Maihofer  1 , Matthew K Nock  10 , Stephan Ripke  5 , Xiaoying Sun  2 , Michael L Thomas  1 , Robert J Ursano  11 , Jordan W Smoller  4   5 , Joel Gelernter  6   11   12   13 ; Army STARRS Collaborators
Affiliations
Meta-Analysis

Genetic risk variants for social anxiety

Murray B Stein et al. Am J Med Genet B Neuropsychiatr Genet. 2017 Mar.

Erratum in

  • Genetic risk variants for social anxiety.
    Stein MB, Chen CY, Jain S, Jensen KP, He F, Heeringa SG, Kessler RC, Maihofer A, Nock MK, Ripke S, Sun X, Thomas ML, Ursano RJ, Smoller JW, Gelernter J; Army STARRS Collaborators. Stein MB, et al. Am J Med Genet B Neuropsychiatr Genet. 2017 Jun;174(4):470-482. doi: 10.1002/ajmg.b.32541. Epub 2017 Apr 27. Am J Med Genet B Neuropsychiatr Genet. 2017. PMID: 28512750 No abstract available.

Corrected and republished in

  • Genetic risk variants for social anxiety.
    Stein MB, Chen CY, Jain S, Jensen KP, He F, Heeringa SG, Kessler RC, Maihofer A, Nock MK, Ripke S, Sun X, Thomas ML, Ursano RJ, Smoller JW, Gelernter J; Army STARRS Collaborators. Stein MB, et al. Am J Med Genet B Neuropsychiatr Genet. 2017 Jun;174(4):470-482. doi: 10.1002/ajmg.b.32541. Epub 2017 Apr 27. Am J Med Genet B Neuropsychiatr Genet. 2017. PMID: 28512750 No abstract available.

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 × 10-4 in 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.

Keywords: anxiety; extraversion; neuroticism; social anxiety; social phobia.

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Conflict of interest statement

Conflict of Interest Disclosure: Dr. Stein has in the last 3 years been a consultant for Healthcare Management Technologies, and Actelion, Dart Neuroscience, Janssen, Oxeia Biopharmaceuticals, Pfizer, Resilience Therapeutics, and Tonix Pharmaceuticals. Dr. Kessler has in the last 3 years been a consultant for Hoffman-La Roche, Inc., Johnson & Johnson Wellness and Prevention, and Sanofi-Aventis Groupe. Dr. Kessler has served on advisory boards for Mensante Corporation, Plus One Health Management, Lake Nona Institute, and U.S. Preventive Medicine. Dr. Kessler owns 25% share in DataStat, Inc. Dr. Smoller is an unpaid member of the Scientific Advisory Board of PsyBrain, Inc. The remaining authors report no disclosures.

Figures

Figure 1
Figure 1. Distribution of social anxiety factor scores in the combined NSS1 and PPDS samples with a normal distribution overlay
Figure 2
Figure 2. Manhattan plots of NSS1, NSS2, and PPDS meta-analysis in (a) African American and (b) European American samples
(a). African American samples, identifying genome-wide significant association for social anxiety with rs78924501 on Chr 1 (λGC = 1.013) (b). European American samples, identifying a genome-wide significant association for social anxiety with rs708012 on Chr 6 (λGC = 1.020)
Figure 3
Figure 3. Regional plots of (a, top panel) rs78924501 on Chr 1 in African American subjects and (b, bottom panel) rs708012 on Chr 6 in European American subjects
Figure 4
Figure 4. Regional plot of rs56081032 (within the Williams Syndrome region) in European Americans
See this image and copyright information in PMC

References

    1. Arbelle S, Benjamin J, Golin M, Kremer I, Belmaker RH, Ebstein RP. Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism. Am J Psychiatry. 2003;160(4):671–676. - PubMed
    1. Barak B, Feng G. Neurobiology of social behavior abnormalities in autism and Williams syndrome. Nat Neurosci. 2016;19(6):647–655. - PMC - PubMed
    1. Bienvenu OJ, Hettema JM, Neale MC, Prescott CA, Kendler KS. Low extraversion and high neuroticism as indices of genetic and environmental risk for social phobia, agoraphobia, and animal phobia. Am J Psychiatry. 2007;164(11):1714–1721. - PubMed
    1. Bienvenu OJ, Samuels JF, Costa PT, Reti IM, Eaton WW, Nestadt G. Anxiety and depressive disorders and the five-factor model of personality: a higher- and lower-order personality trait investigation in a community sample. Depress Anxiety. 2004;20(2):92–97. - PubMed
    1. Bulik-Sullivan B, Finucane HK, Anttila V, Gusev A, Day FR, Loh PR, Duncan L, Perry JR, Patterson N, Robinson EB, Daly MJ, Price AL, Neale BM ReproGen C, Psychiatric Genomics C, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control C. An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015;47(11):1236–1241. - PMC - PubMed

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