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 false(hSNP2false), 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 ( hSNP2=6.3−6.9normal%; 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.

Delayed Sleep Time in African Americans and Depression in a Community-Based Population

“…This approach to sensitivity analysis was selected based on a prior approach to evaluate depression in the Hispanic Community Health Study/Study of Latinos. 30 In addition to weekday bedtime, we also evaluated differences in weekend bedtime as well as used a weighted average of weekday and weekend bedtime:…”

The Role of Gut Mucins in the Etiology of Depression

“…In a 2020 study examining genetic mutations in treatment-refractory depression, pathway analysis revealed significant enrichment in the O-linked glycosylation pathway of mucins (McClain et al, 2020). Additionally, mucin 13 has been specifically implicated in a genome-wide association study of depressive symptoms in a Hispanic community (Ware et al, 2015;Dunn et al, 2018). Taken together, this suggests that stress induced mucus changes may be responsible for microbiota dysbiosis.…”

“…Increased oxidative stress and inflammation, also associated with chronic stress, have been shown to change microvilli structures, further suggesting that stress could tune the microbiome composition (Vanitallie, 2002). Strikingly, two genome-wide association studies have implicated mucins in depression (Dunn et al, 2018;McClain et al, 2020). In a 2020 study examining genetic mutations in treatment-refractory depression, pathway analysis revealed significant enrichment in the O-linked glycosylation pathway of mucins (McClain et al, 2020).…”

The genetic basis of major depression

“…Follow-up studies estimated the genetic correlation between East Asian and European MDD cohorts at 0.33–0.41, while the average genetic correlations between European cohorts was 0.76 (Bigdeli et al, 2017; Wray et al, 2018), and identified trans-ancestral risk variants (Li et al, 2018). In a study of Hispanic/Latino individuals, two out of 22 European depression GWAS loci were replicated (Dunn et al, 2018). The MVP study identified no genome-wide significant loci in over 20 000 African-ancestry patients with major depression (Table 3), and only one of 206 analysed European risk SNPs formally replicated in the African sample (Levey et al, 2020).…”