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

TitleGenome-wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos.
Publication TypePublication
Year2017
AuthorsDunn EC, Sofer T, Gallo LC, Gogarten SM, Kerr KF, Chen C-Y, 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
JournalAm J Med Genet B Neuropsychiatr Genet
Volume174
Issue2
Pagination132-143
Date Published2017 03
ISSN1552-485X
KeywordsAdult, Aged, Anxiety, Anxiety Disorders, ethnic groups, Female, Genetic Predisposition to Disease, genome-wide association study, Genotype, Hispanic Americans, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide
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 (h ) 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 ) 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 ). 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.

DOI10.1002/ajmg.b.32448
Alternate JournalAm J Med Genet B Neuropsychiatr Genet
PubMed ID27159506
PubMed Central IDPMC5501086
Grant ListN01HC95169 / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
K01 MH102403 / MH / NIMH NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
U01 MH087981 / MH / NIMH NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
K24 MH094614 / MH / NIMH NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
L40 MH098379 / MH / NIMH NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
MS#: 
0351
Manuscript Lead/Corresponding Author Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
ECI: 
Yes
Manuscript Status: 
Published