Background
Increased circulating pro-inflammatory markers have repeatedly been associated with major depressive disorder (MDD). However, it remains unclear whether inflammation represents a causal mechanism for MDD, or whether the association is influenced by confounding factors such as body mass index (BMI).

Methods
To better understand this complex relationship, we generated polygenic risk scores (PRS) for MDD and BMI in a population cohort and attempted to isolate the impact these potential risk factors have on adulthood inflammation. Peripheral blood samples were collected as part of the South East London Community Health study, where we generated individualized PRS for MDD and BMI and quantified inflammatory markers using multiplex ELISA-based technology. We performed linear regressions to investigate the effects of PRS for MDD and BMI on inflammatory marker levels.

Results
Out of 35 inflammatory markers, we found a nominal effect of PRS for MDD on interleukin-10. We also found a significant positive effect of BMI on nine inflammatory markers, of which the two most strongly affected markers, interleukin-6 (IL-6) and C-reactive protein (CRP), were also nominally predicted by BMI PRS.

Limitations
The study utilized a cross-sectional design with a moderately sized sample.

Conclusions
Our findings suggest there may not be a shared genetic mechanism contributing to MDD and higher inflammatory marker levels. However, there may be shared genetic etiology between BMI and adulthood levels of CRP and IL-6. Therefore, polygenic risk scores for BMI may represent a useful indicator for heightened levels of inflammation in adulthood.