FinnGen

High-dimensional Mendelian randomization screen of 231 dietary traits and 731 immune phenotypes for insomnia, with cross-release follow-up in FinnGen R12/R13 and population-based validation in NHANES and CHARLS. Prioritized omelette-related intake (protective, OR 0.77) and mixed-fruit (risk, OR 1.29) dietary signals, plus CD33- and HLA-DR-related immune traits. CRP associated with sleep problems in both NHANES and CHARLS. Exploratory cross-design analysis — does not establish causal mechanism.

High-dimensional Mendelian randomization (MR) screens can prioritize candidate dietary and immune pathways for insomnia, but their interpretation is constrained by multiple testing, cross-dataset instability, and limited correspondence between genetic constructs and measured population variables. We conducted an exploratory cross-design analysis that combined MR screening of 231 dietary traits and 731 immune phenotypes, targeted cross-release genetic follow-up in FinnGen R12 and R13, and population-based analyses in NHANES and CHARLS. The targeted R13 follow-up prioritised an omelette-related dietary signal (OR 0.773, 95% CI 0.651-0.917), a mixed-fruit signal (OR 1.285, 95% CI 1.102-1.498), and CD33- and HLA-DR-related immune-cell traits. In NHANES, mapped omelet/scrambled-egg intake was associated with lower odds of sleep problems (OR 0.746, FDR=0.033) and doctor-reported sleep disorder (OR 0.313, FDR=0.008). Higher CRP was associated with sleep problems in NHANES (OR 1.192, FDR=0.001) and restless sleep in CHARLS (OR 1.097, FDR<0.001).