TY - JOUR
T1 - Genetic risk variants for social anxiety
AU - On behalf of the Army STARRS Collaborators
AU - Stein, Murray B.
AU - Chen, Chia Yen
AU - Jain, Sonia
AU - Jensen, Kevin P.
AU - He, Feng
AU - Heeringa, Steven G.
AU - Kessler, Ronald C.
AU - Maihofer, Adam X.
AU - Nock, Matthew K.
AU - Ripke, Stephan
AU - Sun, Xiayong
AU - Thomas, Michael L.
AU - Ursano, Robert J.
AU - Smoller, Jordan W.
AU - Gelernter, Joel
AU - Colpe, Lisa J.
AU - Cersovsky, Col Steven
AU - Aliaga, Pablo A.
AU - Benedek, Col David M.
AU - Benevides, K. Nikki
AU - Borja, Susan
AU - Bromet, Evelyn J.
AU - Brown, Gregory G.
AU - Buckley, Christina
AU - Campbell-Sills, Laura
AU - Cai, Tianxi
AU - Dempsey, Catherine L.
AU - Denenberg, Julie O.
AU - Fullerton, Carol S.
AU - Gebler, Nancy
AU - Gifford, Robert K.
AU - Gilman, Stephen E.
AU - Holloway, Marjan G.
AU - Hurwitz, Paul E.
AU - Kao, Tzu Cheg
AU - Koenen, Karestan C.
AU - Lewandowski-Romps, Lisa
AU - Mash, Holly Herberman
AU - McCarroll, James E.
AU - Mitchell, Colter
AU - Naifeh, James A.
AU - Ng, Tsz Hin Hinz
AU - Raman, Rema
AU - Ramsawh, Holly J.
AU - Rosellini, Anthony Joseph
AU - Sampson, Nancy A.
AU - Lcdrpatcho, Santiago
AU - Scanlon, Michaelle
AU - Street, Amy
AU - Vegella, Patti L.
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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 (h 2 g = 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 (r g = −0.52, se = 0.22, P = 0.02) but not with neuroticism (r g = 0.05, se = 0.22, P = 0.81) or with an anxiety disorder factor score (r g = 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.
AB - 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 (h 2 g = 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 (r g = −0.52, se = 0.22, P = 0.02) but not with neuroticism (r g = 0.05, se = 0.22, P = 0.81) or with an anxiety disorder factor score (r g = 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.
KW - anxiety
KW - extraversion
KW - neuroticism
KW - social anxiety
KW - social phobia
UR - http://www.scopus.com/inward/record.url?scp=85013827336&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.32520
DO - 10.1002/ajmg.b.32520
M3 - Article
C2 - 28224735
AN - SCOPUS:85013827336
SN - 1552-4841
VL - 174
SP - 120
EP - 131
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 2
ER -