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Genome‐wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos
Author(s) -
Dunn Erin C.,
Sofer Tamar,
Gallo Linda C.,
Gogarten Stephanie M.,
Kerr Kathleen F.,
Chen ChiaYen,
Stein Murray B.,
Ursano Robert J.,
Guo Xiuqing,
Jia Yucheng,
Qi Qibin,
Rotter Jerome I.,
Argos Maria,
Cai Jianwen,
Penedo Frank J.,
Perreira Krista,
WassertheilSmoller Sylvia,
Smoller Jordan W.
Publication year - 2017
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32448
Subject(s) - genome wide association study , heritability , generalized anxiety disorder , anxiety , genetic association , medicine , psychiatry , clinical psychology , psychology , genetics , single nucleotide polymorphism , biology , genotype , gene
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 (h 2 SNP ) 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.