Objective:

To investigate the associations of polygenic risk scores (PRS) for C-reactive protein (CRP) and interleukin 6 (IL-6) with cardiometabolic outcomes in patients with schizophrenia spectrum disorders (SSDs).

Approach:

• Study Design: The study utilized data from 671 patients with SSDs from the longitudinal Dutch Genetic Risk and Outcome in Psychosis (GROUP) study.
• Polygenic Risk Score Construction: Seven PRSCRP and seven PRSIL-6 were constructed using clumping and threshold methods based on genome-wide association studies.
• Outcome Measurement: Eleven cardiometabolic outcomes were measured three years post-diagnosis, including BMI, waist circumference, lipid levels, blood pressures, glycaemic markers, and a metabolic composite score.
• Statistical Analysis: Linear regression models adjusted for age, sex, and population substructure were used to test associations, with multiple testing correction and bootstrapping for validation.

Key Findings:

• Higher standardized PRSCRP was significantly associated with increased BMI (βPt_0.5 = 0.64, 95%CI=0.21-1.02, Pbootstapping = 0.003) and waist circumference (βPt_0.5 = 2.25, 95%CI=1.00-3.53, Pbootstapping < 0.001), explaining up to 1.85% variance in BMI and 2.52% in waist circumference.
• Nominal associations were found between PRSCRP and triglycerides levels (βPt_0.2 = 0.13, 95%CI=0.01-0.26, Pbootstapping = 0.036) and metabolic composite score (βPt_0.2 = 0.14, 95%CI=0.04-0.24, Pbootstapping = 0.006), but did not remain significant after correction for multiple testing.
• Associations between PRSIL-6 and HbA1c level (βPt_5e06=-0.66, 95%CI=-1.26 to -0.05, Pbootstapping = 0.033) were also observed but did not survive multiple testing correction.

Interpretation:

Limitations:

• The study's findings may not be generalizable beyond the SSD population.
• Associations observed may be influenced by unmeasured confounding factors.

Conclusion: