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Predicting psychiatric and cardiometabolic outcomes using psychiatric polygenic scores: evidence from three northern European countries

Predicting psychiatric and cardiometabolic outcomes with psychiatric polygenic scores: evidence from three northern european countries

Susceptibility to major depressive disorder emerges as the principal source of shared common-variant genetic susceptibility between mental disorders and cardiometabolic diseases.

The study aimed to examine whether the shared genetic susceptibility underlying the co-occurrence of mental disorders and cardiometabolic diseases (CMDs) is disorder-specific or reflects cross-disorder pleiotropy, and to investigate the contributions of lifestyle and socioeconomic factors. Among 355,717 participants from the Swedish Twin Registry, the Norwegian MoBa cohort, and the Estonian Biobank, the researchers examined associations between polygenic scores (PGSs) for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), anxiety disorders, post-traumatic stress disorder (PTSD), bipolar disorder, and schizophrenia and clinical diagnoses of these disorders and ten clinically diagnosed cardiometabolic diseases; ICD-10 diagnoses were harmonized across national health registries, and models were mutually adjusted for all six PGSs, as well as body mass index, smoking, and education. All psychiatric PGSs were associated with their corresponding clinical diagnoses, with the strongest independent associations observed for schizophrenia and bipolar disorder PGSs. Genetic susceptibility to ADHD, MDD, anxiety disorders, and PTSD was associated with a higher risk of cardiometabolic disease, whereas susceptibility to schizophrenia was associated with a lower risk. The MDD PGS showed the most consistent associations with cardiometabolic diseases, which persisted after adjustment for cross-disorder pleiotropy, lifestyle, and education; associations involving the ADHD, anxiety disorder, and PTSD PGSs were substantially attenuated after adjustment for the MDD PGS. The authors conclude that common-variant genetic risk is unlikely to explain the co-occurrence of schizophrenia and cardiometabolic diseases.

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