@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 = "Hispanics/Latinos, anxiety, genetic association study",
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.}",
note = "Funding Information: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01- HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079, UL1-TR-000040, and DK063491. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The Army Study of Risk and Resilience in Servicemembers (Army STARRS) was sponsored by the Department of the Army and funded under cooperative agreement number U01MH087981 with the U.S. Department of Health and Human Services, National Institutes of Health, and National Institute of Mental Health (NIH/NIMH). The contents are solely the responsibility of the authors and do not necessarily represent the views of the Department of Health and Human Services, the National Institutes of Health, the Veterans Administration, Department of the Army, or the Department of Defense. The current study is supported the National Institute of Mental Health of the National Institutes of Health under Award Number K01MH102403 (Dunn) and K24MH094614 (Smoller), by a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Dunn), and a Tepper Family MGH Research Scholar Award (Smoller). The authors thank Sandy Li and Jenna Kiely for their assistance in conducting the literature search for this paper. The authors also thank the staff and participants of HCHS/SOL for their important contributions. A complete list of staff and investigators has been provided by Lavange et al. [] and is also available on the study website http://www.cscc.unc.edu/hchs/. Publisher Copyright: {\textcopyright} 2016 Wiley Periodicals, Inc.",
year = "2017",
month = mar,
day = "1",
doi = "10.1002/ajmg.b.32448",
language = "English (US)",
volume = "174",
pages = "132--143",
journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",
number = "2",
}
