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

Joeri Meijsen*, Kejia Hu, Morten D. Krebs, Georgios Athanasiadis, Sarah Washbrook, Richard Zetterberg, Raquel Nogueira Avelar e Silva, John 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. AndreassenThomas M. Werge, Fang Fang, Alfonso Buil*

*Corresponding author

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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.

TidsskriftNature Communications
Udgave nummer1
StatusUdgivet - dec. 2024

Bibliografisk note

Funding Information:
This research was supported by: the European Union\u2019s Horizon 2020 Research and Innovation Programme: the \u201Cpredicting comorbid cardiovascular disease in individuals with mental disorder by decoding disease mechanisms\u201D project (CoMorMent, grant number 847776, to J.M., J.B., A.B., U.V., D.M., Y.L., T.W., O.A., and F.F.); the Danish National Research Foundation (grant number DNRF148); the US National Institutes of Health study on extreme MDD (R01 MH123724, to J.M., J.R.S., Y.L., and A.B.); the European Research Council (grant agreement ID 101042183, to Y.L.),.the Sir Henry Wellcome Postdoctoral Fellowship (Reference 213674/Z/18/Z, to D.H.); the Research Council of Norway (RCN grants 324499, 324252, 223273, to O.A.); the Stiftelsen Kristian Gerhard Jebsen (grants SKGJ-MED-008 and SKGJ-MED-021, to O.A).; the Laureate Grant Award from the Novo Nordisk Foundation (Grant No: NNF22OC0071010, to N.M.); European Research Council Consolidator grant (StressGene, Grant nr. 726413 to U.V.), and Icelandic Research fund (to U.V.). The iPSYCH Initiative is funded by the Lundbeck Foundation (Grant Nos. R268-2016-3925, R102-A9118, and R155-2014-1724), the Mental Health Services Capital Region of Denmark, University of Copenhagen, Aarhus University, and the University Hospital in Aarhus. Genotyping of iPSYCH samples was supported by grants from the Lundbeck Foundation, the Stanley Foundation, the Simons Foundation (Grant No. SFARI 311789), and the National Institutes of Mental Health (Grant No. 5U01MH094432-02). The iPSYCH Initiative uses the Danish National Biobank resource that is supported by the Novo Nordisk Foundation.

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