BIONIC MDD 2025

MDD 2025 (click to download the file). Huider et al. 2025, Genetics of Major Depressive Disorder in a Homogeneous Population with Uniform Phenotyping, submitted.

In this genome-wide association mega-analysis of 16 Dutch studies united in the BIObanks Netherlands Internet Collaboration (BIONIC) we found one novel genetic association with lifetime major depressive disorder (MDD), rs3818852 linked to the PALMD gene on chromosome 1. This signal was separate from the global MDD signal and might be unique to this population. In follow-up analyses we identified putative MDD predictors and outcomes in immune-, cardiometabolic, work-environment and lifestyle-related traits. We found that the global MDD polygenic score (PGS) significantly explained 4% of variance in BIONIC MDD, and BIONIC MDD PGS explained 0.29% of variance in broadly defined MDD in UKBiobank, with a higher value for strictly defined MDD (0.39%). We found that twins from concordantly affected twin pairs had higher MDD PGS than discordant twins, and discordant twins had higher MDD PGS than concordantly unaffected twins. Finally, we found limited evidence for bias due to assortative mating in PGS prediction.