Depression

Major depression is highly polygenic, meaning very many variants each contribute a little. This score takes 17 of the strongest of them, which makes it a rough and narrow summary of a genetic tendency that circumstances act on.

What this depression score reads

This is PGS004591, a 17-variant score used by Li and colleagues in a 2023 BMC Medicine study of how long-term air pollution exposure and genetic susceptibility combine in major depressive disorder. The variants come from a GWAS of 326,113 European-ancestry participants.

Seventeen variants is a narrow slice of this trait. Genome-wide studies of depression have identified more than a hundred loci, each contributing very little, which is characteristic of a condition where genetic effects are numerous, tiny and heavily entangled with circumstance.

How well it predicts depression

In 340,408 UK Biobank participants, of whom 14,172 developed major depressive disorder, the hazard ratio was 1.10 per interquartile increase in the score, adjusted for age, sex, education, employment, income and deprivation.

A hazard ratio of 1.10 across the middle half of the distribution is a weak signal, detectable only because the cohort is enormous. It says almost nothing about an individual.

What the study behind the score was actually about

The paper used this score to study interaction rather than prediction. People in the top third of genetic risk with high fine particulate air pollution exposure had a hazard ratio of 1.34 compared with people in the bottom third with low exposure, and the authors concluded that lifestyle and environment modify how genetic susceptibility plays out.

That is the useful framing for any depression polygenic score: it is a small background tendency that circumstances act on, not a property that determines outcomes.

What this score does not capture

Nearly everything that actually predicts depression sits outside a DNA file: bereavement and loss, trauma, chronic illness and pain, isolation, financial strain, sleep disruption, alcohol and other substances, thyroid disease, and the postnatal period.

Depression is also diagnosed clinically, through how a person is feeling and functioning, not by any biological test. A percentile here is not a screening tool and should not be used as one.

If this is a live question for you

Nothing in a polygenic score changes what helps. If you are struggling with low mood, loss of interest, hopelessness or thoughts of self-harm, that is worth raising with a doctor or a mental health service now, whatever your genotype says. Effective treatments exist and none of them depend on these 17 variants.

How much of this score your file covers

All 17 variants in the published score are present in a standard consumer DNA file, so this reconstructs the published score in full.

Common questions

Does a high depression polygenic score mean I will become depressed? No. The measured effect was a hazard ratio of 1.10 per interquartile increase in a cohort of 340,000 people, which is a group-level signal that carries essentially no predictive value for an individual. Circumstances, health and support matter far more.

Can this score tell me which antidepressant would work? No. That question belongs to pharmacogenomics, where this site reads specific drug-metabolism genes, and even there the evidence guides dosing and tolerance rather than which medication will help. This score has nothing to say about treatment.

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