Genome-wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos

Erin C. Dunn, Tamar Sofer, Linda C. Gallo, Stephanie M. Gogarten, Kathleen F. Kerr, Chia Yen Chen, Murray B. Stein, Robert J. Ursano, Xiuqing Guo, Yucheng Jia, Qibin Qi, Jerome I. Rotter, Maria Argos, Jianwen Cai, Frank J. Penedo, Krista Perreira, Sylvia Wassertheil-Smoller, Jordan W. Smoller

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 (h2 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.

Fingerprint

Genome-Wide Association Study
Anxiety Disorders
Hispanic Americans
Anxiety
Health
Single Nucleotide Polymorphism
Genome
Women's Health
Diagnostic and Statistical Manual of Mental Disorders
Psychiatry
Meta-Analysis
Atherosclerosis

Keywords

  • Anxiety
  • Genetic association study
  • Hispanics/Latinos

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Genome-wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos. / Dunn, Erin C.; Sofer, Tamar; Gallo, Linda C.; Gogarten, Stephanie M.; Kerr, Kathleen F.; Chen, Chia Yen; Stein, Murray B.; Ursano, Robert J.; Guo, Xiuqing; Jia, Yucheng; Qi, Qibin; Rotter, Jerome I.; Argos, Maria; Cai, Jianwen; Penedo, Frank J.; Perreira, Krista; Wassertheil-Smoller, Sylvia; Smoller, Jordan W.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 2016.

Research output: Contribution to journalArticle

Dunn, EC, Sofer, T, Gallo, LC, Gogarten, SM, Kerr, KF, Chen, CY, Stein, MB, Ursano, RJ, Guo, X, Jia, Y, Qi, Q, Rotter, JI, Argos, M, Cai, J, Penedo, FJ, Perreira, K, Wassertheil-Smoller, S & Smoller, JW 2016, 'Genome-wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. https://doi.org/10.1002/ajmg.b.32448
Dunn, Erin C. ; Sofer, Tamar ; Gallo, Linda C. ; Gogarten, Stephanie M. ; Kerr, Kathleen F. ; Chen, Chia Yen ; Stein, Murray B. ; Ursano, Robert J. ; Guo, Xiuqing ; Jia, Yucheng ; Qi, Qibin ; Rotter, Jerome I. ; Argos, Maria ; Cai, Jianwen ; Penedo, Frank J. ; Perreira, Krista ; Wassertheil-Smoller, Sylvia ; Smoller, Jordan W. / Genome-wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2016.
@article{78e1f9ff2e6042ecb20b8a9cfc1a4b7f,
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 (h2 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.",
keywords = "Anxiety, Genetic association study, Hispanics/Latinos",
author = "Dunn, {Erin C.} and Tamar Sofer and Gallo, {Linda C.} and Gogarten, {Stephanie M.} and Kerr, {Kathleen F.} and Chen, {Chia Yen} and Stein, {Murray B.} and Ursano, {Robert J.} and Xiuqing Guo and Yucheng Jia and Qibin Qi and Rotter, {Jerome I.} and Maria Argos and Jianwen Cai and Penedo, {Frank J.} and Krista Perreira and Sylvia Wassertheil-Smoller and Smoller, {Jordan W.}",
year = "2016",
doi = "10.1002/ajmg.b.32448",
language = "English (US)",
journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Genome-wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos

AU - Dunn, Erin C.

AU - Sofer, Tamar

AU - Gallo, Linda C.

AU - Gogarten, Stephanie M.

AU - Kerr, Kathleen F.

AU - Chen, Chia Yen

AU - Stein, Murray B.

AU - Ursano, Robert J.

AU - Guo, Xiuqing

AU - Jia, Yucheng

AU - Qi, Qibin

AU - Rotter, Jerome I.

AU - Argos, Maria

AU - Cai, Jianwen

AU - Penedo, Frank J.

AU - Perreira, Krista

AU - Wassertheil-Smoller, Sylvia

AU - Smoller, Jordan W.

PY - 2016

Y1 - 2016

N2 - 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 (h2 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.

AB - 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 (h2 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.

KW - Anxiety

KW - Genetic association study

KW - Hispanics/Latinos

UR - http://www.scopus.com/inward/record.url?scp=84966460058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84966460058&partnerID=8YFLogxK

U2 - 10.1002/ajmg.b.32448

DO - 10.1002/ajmg.b.32448

M3 - Article

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

SN - 1552-4841

ER -