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Kalman, Janos L.; Papiol, Sergi; Grigoroiu-Serbanescu, Maria; Adorjan, Kristina; Anderson-Schmidt, Heike; Brosch, Katharina; Budde, Monika; Comes, Ashley L.; Gade, Katrin; Forstner, Andreas; Grotegerd, Dominik; Hahn, Tim; Heilbronner, Maria; Heilbronner, Urs; Heilmann-Heimbach, Stefanie; Kloehn-Saghatolislam, Farah; Kohshour, Mojtaba Oraki; Meinert, Susanne; Meller, Tina; Mullins, Niamh; Nenadic, Igor; Noethen, Markus M.; Pfarr, Julia-Katharina; Reich-Erkelenz, Daniela; Rietschel, Marcella; Ringwald, Kai G.; Schaupp, Sabrina; Schulte, Eva C.; Senner, Fanny; Stein, Frederike; Streit, Fabian; Vogl, Thomas; Falkai, Peter; Dannlowski, Udo; Kircher, Tilo; Schulze, Thomas G. and Andlauer, Till F. M. (2021): Genetic risk for psychiatric illness is associated with the number of hospitalizations of bipolar disorder patients. In: Journal of Affective Disorders, Vol. 296: pp. 532-540

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Objectives: Bipolar disorder (BD) has a highly heterogeneous clinical course that is characterized by relapses and increased health care utilization in a significant fraction of patients. A thorough understanding of factors influencing illness course is essential for predicting disorder severity and developing targeted therapies. Methods: We performed polygenic score analyses in four cohorts (N = 954) to test whether the genetic risk for BD, schizophrenia, or major depression is associated with a severe course of BD. We analyzed BD patients with a minimum illness duration of five years. The severity of the disease course was assessed by using the number of hospitalizations in a mental health facility and a composite measure of longitudinal illness severity (OPCRIT item 90). Results: Our analyses showed that higher polygenic scores for BD (beta = 0.11, SE = 0.03, p = 1.17 x 10(-3)) and schizophrenia (beta = 0.09, SE = 0.03, p = 4.24 x 10(-3)), but not for major depression, were associated with more hospitalizations. None of the investigated polygenic scores was associated with the composite measure of longitudinal illness severity (OPCRIT item 90). Limitations: We could not account for non-genetic influences on disease course. Our clinical sample contained more severe cases. Conclusions: This study demonstrates that the genetic risk burden for psychiatric illness is associated with increased health care utilization, a proxy for disease severity, in BD patients. The findings are in line with previous observations made for patients diagnosed with schizophrenia or major depression. Therefore, in the future psychiatric disorder polygenic scores might become helpful for stratifying patients with high risk of a chronic manifestation and predicting disease course.

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