Depression (Self-Reported Symptoms)

This catalogue already has a page for Major Depressive Disorder, built from studies of people with a clinical diagnosis compared against controls. This page holds variants from a different kind of study — self-reported symptoms and broad, population-scale definitions of depression rather than a structured clinical diagnosis — and the difference is worth stating rather than glossing over.

Four studies, one growing self-report picture

The oldest source here, Okbay et al. 2016, ran genome-wide association analyses across three related but distinct measures in very large population samples: subjective well-being (298,420 participants), depressive symptoms (161,460 participants), and neuroticism (170,911 participants). The depressive-symptoms measure was a self-report symptom scale in general-population cohorts, not a clinical diagnosis, and the paper reports two genome-wide significant loci for it specifically. Five of this page's variants come from that study, including rs782212, near NEGR1 (P = 7.0 × 10⁻¹¹) — a gene better known elsewhere in this catalogue's territory as one of the most consistently replicated genes in body-mass-index and obesity genetics, its role in mood far less mechanistically worked out.

Turley et al. 2018 introduced a statistical method called MTAG (multi-trait analysis of GWAS) — the same technique behind the Howard et al. 2018 "broad depression" study above — and demonstrated it by jointly re-analysing the same three traits Okbay et al. 2016 studied separately: depressive symptoms, neuroticism, and subjective well-being. Against the single-trait totals of 32, 9, and 13 genome-wide-significant loci, the joint MTAG analysis raised those counts to 64, 37, and 49 respectively — roughly doubling what the depressive-symptoms analysis alone had found, and raising the variance explained by polygenic scores by about 25%. Eighteen of this page's variants come from this reanalysis.

Wray et al. 2018, from the Psychiatric Genomics Consortium, meta-analysed 135,458 cases and 344,901 controls and identified 44 independent, genome-wide-significant loci — eight of which are held on this page. Its case definition combines clinical, registry and self-report ascertainment across contributing cohorts rather than a single structured interview, part of why GWAS Catalog tags these variants under the same "Depression" trait as the self-report studies here rather than filing them exclusively under a clinical-diagnosis label.

Howard et al. 2018 studied 322,580 UK Biobank participants across three related depression phenotypes — broad depression, probable major depressive disorder, and ICD-coded major depressive disorder — and found 17 independent genome-wide-significant loci across the three combined, 14 of them novel. This page's 17 newest variants are GWAS Catalog's curated associations for the "broad depression" phenotype specifically: self-reported help-seeking for a mental health difficulty, not a diagnosis.

The largest source, Howard et al. 2019, meta-analysed 807,553 individuals (246,363 cases and 561,190 controls) across the three largest genome-wide association studies of depression available at the time, identifying 102 independent variants, 269 genes and 15 gene sets, with an enrichment signal in prefrontal brain regions. In an independent replication sample of 1,306,354 people, 87 of the 102 variants held up after correction for multiple testing. Thirty of this page's variants come from this meta-analysis.

Why this is a separate page

A self-reported symptom scale or a broad, population-scale definition of depression and a clinical case-control diagnosis are related but genuinely different constructs in psychiatric genetics — studies of the two do not always find the same loci, and treating them as interchangeable would overstate what any of them shows. Keeping this page separate from Major Depressive Disorder is the accurate description of what these four studies actually measured, not a duplication of the same finding under two names.