Polygenic risk score
Major Depressive Disorder (MDD)
ICD-11 6A70 · Mood disorders
The Major Depressive Disorder (MDD) polygenic risk score summarizes cumulative common-variant loading across hundreds of loci identified in the largest GWAS of depression. Depression has a massive GWAS cohort but modest predictive accuracy — life events and social context carry more predictive weight than any PRS.
Depression is the most heritable common psychiatric condition by absolute affected population, yet the polygenic risk score explains only ~2–4% of variance in liability — a high score does not mean you will become depressed.
At a glance
Depression is the most heritable common psychiatric condition in absolute patient numbers and one of the largest GWAS sample sizes in any human trait. Your score reflects cumulative common-variant loading across hundreds of loci.
Major Depressive Disorder is a common, recurrent mood disorder. Twin heritability is estimated around 35-40% — lower than ADHD or schizophrenia but on a much larger affected population. The latest PGC MDD GWAS pools across hundreds of thousands of cases and identifies hundreds of genome-wide significant loci, distributed across the genome with very small individual effects.
What the GWAS actually found
The Wray et al. 2018 PGC meta-analysis (Nature Genetics) combined 135,458 MDD cases and 344,901 controls and identified 44 genome-wide significant loci. The per-variant effects are tiny; the signal is distributed across the genome consistent with a highly polygenic architecture.
Twin-study heritability for MDD sits at roughly 35–40% — lower than ADHD or schizophrenia, but on a much larger affected population. Subsequent meta-analyses including UK Biobank participants have pushed loci counts substantially higher, though the PRS variance explained in independent samples remains modest.
How to read your percentile
Below 25th
Lower common-variant liability than most of the reference cohort. Depression remains possible — most risk is captured by life context, not genetics.
25th–75th
Typical range — near the population average. Your PRS is not clinically informative at this percentile.
Above 75th
Elevated common-variant liability. Consider the score one small factor among many; modifiable factors (sleep, exercise, social connection) have larger effect sizes in interventional trials.
What this does not tell you
A depression PRS cannot diagnose MDD, predict whether you will experience a depressive episode, or identify which treatment will work for you. Depression is strongly shaped by modifiable factors — sleep, social connection, physical activity, trauma exposure — that a PRS cannot see.
The score is specific to the diagnostic construct used in the PGC meta-analysis (broadly defined MDD with varying inclusion criteria across cohorts). It does not distinguish melancholic from atypical, unipolar from bipolar-spectrum, or reactive from endogenous phenotypes. Cross-ancestry accuracy is reduced outside European populations.
Related traits
Major Depressive Disorder (MDD) shares common-variant architecture with several other psychiatric conditions. Genetic correlations (rg) reflect how often the same variants move risk for both traits in the same direction.
Frequently asked questions
Can this score predict whether I will get depressed?
No. A depression PRS is a probabilistic population-level signal. It cannot predict whether or when you will experience a depressive episode. Environmental and social factors — which a PRS cannot measure — are the dominant drivers of whether genetic liability translates into clinical depression.
Why is the MDD PRS accuracy lower than schizophrenia's?
Depression has a much larger and more heterogeneous cohort, with diagnostic definitions that vary across studies. Schizophrenia GWAS have tighter case definitions and higher per-SNP effect sizes. The MDD PRS explains roughly 2–4% of variance in liability versus ~9% for schizophrenia.
Should I change my treatment based on this score?
No. This report is a research and educational tool, not a clinical one. Treatment decisions should be made with a qualified clinician based on your symptoms, history, and response to prior interventions — not on a PRS.
Does the score distinguish subtypes of depression?
No. The PGC GWAS used a broadly defined MDD construct. The resulting PRS does not differentiate melancholic, atypical, seasonal, or treatment-resistant subtypes. Genetic architecture of MDD subtypes is an active area of research.
Sources
- Wray et al. 2018, Nature Genetics 50:668–681. doi.org/10.1038/s41588-018-0090-3
- PGC Major Depressive Disorder Working Group. pgc.unc.edu/for-researchers/working-groups/major-depressive-disorder-workgroup/
- Purves et al. 2020 — Anxiety and MDD genetic overlap. doi.org/10.1038/s41380-019-0559-1
Want your own polygenic risk score?
Upload your AncestryDNA or 23andMe raw data to get the ADHD and Anxiety preview free, or unlock all 13 traits for $29 (launch pricing).
Upload your file