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

ABSTRACT: Although genome-wide association studies (GWAS) have identified several variants linked to depression, few GWAS of non-European populations have been performed. We conducted a genome-wide analysis of depression in a large, population-based sample of Hispanics/Latinos. Data came from 12,310 adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Past-week depressive symptoms were assessed using the 10-item Center for Epidemiological Studies of Depression Scale. Three phenotypes were examined: a total depression score, a total score modified to account for psychiatric medication use, and a score excluding anti-depressant medication users. We estimated heritability due to common variants (h2SNP), and performed a GWAS of the three phenotypes. Replication was attempted in three independent Hispanic/Latino cohorts. We also performed sex-stratified analyses, analyzed a binary trait indicating probable depression, and conducted three trans-ethnic analyses. The three phenotypes exhibited significant heritability (h2SNP?=?6.3-6.9%; p?=?.002) in the total sample. No SNPs were genome-wide significant in analyses of the three phenotypes or the binary indicator of probable depression. In sex-stratified analyses, seven genome-wide significant SNPs (one in females; six in males) were identified, though none were supported through replication. Four out of 24 loci identified in prior GWAS were nominally associated in HCHS/SOL. There was no evidence of overlap in genetic risk factors across ancestry groups, though this may have been due to low power. We conducted the largest GWAS of depression-related phenotypes in Hispanic/Latino adults. Results underscore the genetic complexity of depressive symptoms as a phenotype in this population and suggest the need for much larger samples.

SUBMITTER: Dunn EC

PROVIDER: S-EPMC6192675 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Dunn Erin C EC Sofer Tamar T Wang Min-Jung MJ Soare Thomas W TW Gallo Linda C LC Gogarten Stephanie M SM Kerr Kathleen F KF Chen Chia-Yen CY Stein Murray B MB Ursano Robert J RJ Guo Xiuqing X Jia Yucheng Y Yao Jie J Rotter Jerome I JI Argos Maria M Cai Jianwen J Perreira Krista K Wassertheil-Smoller Sylvia S Smoller Jordan W JW

Journal of psychiatric research 20171216

Although genome-wide association studies (GWAS) have identified several variants linked to depression, few GWAS of non-European populations have been performed. We conducted a genome-wide analysis of depression in a large, population-based sample of Hispanics/Latinos. Data came from 12,310 adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Past-week depressive symptoms were assessed using the 10-item Center for Epidemiological Studies of Depression Scale. Three phenotypes ...[more]

PMID: 29505938

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Project description:Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from genome-wide association studies (GWASs) has highlighted several potential novel loci. Here, the authors report the first GWAS of CP among a large community-based sample of Hispanics/Latinos. The authors interrogated a quantitative trait of CP (mean interproximal clinical attachment level determined by full-mouth periodontal examinations) among 10,935 adult participants (mean age: 45 y, range: 18 to 76 y) from the Hispanic Community Health Study / Study of Latinos. Genotyping was done with a custom Illumina Omni2.5M array, and imputation to approximately 20 million single-nucleotide polymorphisms was based on the 1000 Genomes Project phase 1 reference panel. Analyses were based on linear mixed models adjusting for sex, age, study design features, ancestry, and kinship and employed a conventional P < 5 × 10-8 statistical significance threshold. The authors identified a genome-wide significant association signal in the 1q42.2 locus ( TSNAX-DISC1 noncoding RNA, lead single-nucleotide polymorphism: rs149133391, minor allele [C] frequency = 0.01, P = 7.9 × 10-9) and 4 more loci with suggestive evidence of association ( P < 5 × 10-6): 1q22 (rs13373934), 5p15.33 (rs186066047), 6p22.3 (rs10456847), and 11p15.1 (rs75715012). We tested these loci for replication in independent samples of European-American ( n = 4,402) and African-American ( n = 908) participants of the Atherosclerosis Risk in Communities study. There was no replication among the European Americans; however, the TSNAX-DISC1 locus replicated in the African-American sample (rs149133391, minor allele frequency = 0.02, P = 9.1 × 10-3), while the 1q22 locus was directionally concordant and nominally significant (rs13373934, P = 4.0 × 10-2). This discovery GWAS of interproximal clinical attachment level-a measure of lifetime periodontal tissue destruction-was conducted in a large, community-based sample of Hispanic/Latinos. It identified a genome-wide significant locus that was independently replicated in an African-American population. Identifying this genetic marker offers direction for interrogation in subsequent genomic and experimental studies of CP.

Project description:BackgroundThe Environmental Affordances Model (EAM) proposes that the effects of chronic stress on depression are moderated by unhealthy behaviors and race/ethnicity. The unique social structures and contexts of Hispanics/Latinos in the U.S. may influence such relationships. This study evaluated whether unhealthy behaviors weakened the relationship between allostatic load, a measure of chronic stress, and future elevated depressive symptoms among Hispanic Community Health Study/Study of Latinos participants.MethodsLongitudinal data (2008-2011 and 2014-2017) from 11,623 participants were analyzed. The exposure was allostatic load, an index of twelve established biomarkers categorized using clinically relevant cut points, at Visit 1. Elevated depressive symptoms were operationalized as a score of ≥10 (out of 30) on the CES-D 10 at Visit 2. An index of unhealthy behaviors, with one point each for cigarette smoking, excessive/binge drinking, sedentary behavior, and poor diet quality at Visit 1, was examined as an effect modifier. Multivariable logistic regression, in the overall sample and among Mexicans specifically and adjusted for demographic characteristics and elevated depressive symptoms at Visit 1, was used to model allostatic load, unhealthy behavior index (range: 0-4), and their interaction in relation to elevated depressive symptoms at Visit 2.ResultsOverall, greater allostatic load was associated with higher odds of elevated depressive symptoms after at least 6 years (aOR = 1.06, 95% CI = 1.01, 1.10). Overall, individuals with greater allostatic load and an unhealthy behavior index = 1, compared to those with an unhealthy behavior index = 0, had lower odds of elevated depressive symptoms at follow-up (aβ = -0.065, 95% CI = -0.12, -0.007).ConclusionsThe relationship between chronic stress and depression was partially moderated among Hispanics/Latinos who engaged in unhealthy behavior, which may have reduced their risk of elevated depressive symptoms given more chronic stress.

Dataset Information

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

Publications

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

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