Gene-based association analysis of depression risk among European ancestry Parkinson's disease patients.
Hanwen Wang, Kimberly Paul, Cynthia Kusters et al.
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In 30 seconds
This gene-based association analysis and meta-analysis examined common and low-frequency genetic variants related to depression among European-ancestry patients with Parkinson’s disease (PD) in three population-based studies. KRTCAP2 was significantly associated with self-reported depression diagnosis after false discovery rate correction; greater genetic burden in this gene was associated with 20% increased odds of depression (OR = 1.20, 95% CI: 1.04-1.38). A depression polygenic risk score was also associated with depression diagnosis, whereas a PD polygenic risk score was not. The findings suggest both shared and PD-related genetic contributions.
Key findings
- KRTCAP2 genetic burden was associated with 20% increased odds of depression (OR = 1.20, 95% CI: 1.04-1.38).
- A depression polygenic risk score was associated with depression diagnosis in PD (OR = 1.26, 95% CI: 1.13-1.40); a PD polygenic risk score was not.
- SPPL3 and ERBB4 were associated with depression diagnosis history, while FNIP2 was associated with current depressive symptoms.
Why it matters
Depression is a disabling non-motor feature of PD, and these results suggest its genetic liability may partly overlap with depression risk in the general population while also involving PD-related genes. Identifying such associations can inform understanding of depression’s biological heterogeneity in PD, although the findings do not establish mechanisms or indicate that genetic testing can guide care.
What to keep in mind
The analysis was restricted to European-ancestry patients, and the reported associations do not establish causal effects.