Recent epidemiological studies suggest that polygenic risk for depression is associated with elevated white blood cell count, indicating shared genetic mechanisms between depression as a psychiatric disorder and the pro-inflammatory states often observed in clinical depression. However, the effects of aging on depressive symptoms and inflammation are not often fully appreciated in these studies, despite known variation across the human lifespan. To investigate the interaction of polygenic risk for depression and age on white blood cell count, we calculated depression polygenic risk scores (PRS) in 324,098 individuals from the UK Biobank (UKB) and 22,758 individuals from the Canadian Longitudinal Study on Aging (CLSA). Linear regression models of white blood cell count were fit to each sample, including interaction effects between age and the depression PRS. Significant age by PRS interaction effects were found in both samples (UKB interaction term: t=-2.9, p=3.7x10-3; CLSA interaction term: t=-2.6, p=9.0x10-3). While the previously reported main positive association between PRS and increasing white blood cell count was observed, we show in this study that the strength of the association diminishes with increasing age. Considering this potential age-dependency, these findings should encourage efforts to uncover genome-wide markers of late-life depression, which are needed to fully understand these age-related interaction effects.

The authors have declared no competing interest.

ET is supported by an Ontario Graduate Scholarship. DF is supported by the Krembil Foundation, the Koerner Family Foundation New Scientist Award, the Canadian Institutes of Health Research (CIHR), and the CAMH Discovery Fund. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

UK Biobank. Available at: https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access Canadian Longitudinal Study on Aging. Available at: https://www.clsa-elcv.ca/access

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