Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians

Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

Joeri Meijsen, Kejia Hu, Morten D. Krebs, Georgios Athanasiadis, Sarah Washbrook, Richard Zetterberg, Raquel Nogueira Avelar e Silva, John R. Shorter, Jesper R. Gådin, Jacob Bergstedt, David M. Howard, Weimin Ye, Yi Lu, Unnur A. Valdimarsdóttir, Andrés Ingason, Dorte Helenius, Oleguer Plana-Ripoll, John J. McGrath, Nadia Micali, Ole A. Andreassen, Thomas M. Werge, Fang Fang, Alfonso Buil