Characterizing the Shared Genetic Underpinnings of Schizophrenia and Cardiovascular Disease Risk Factors

作者：Linn Rødevand, Zillur Rahman, Guy Hindley, Olav B. Smeland, Oleksandr Frei, Tahir Filiz Tekin, Gleda Kutrolli, Shahram Bahrami, Eva Hoseth, Alexey Shadrin, Aihua Lin, Srdjan Djurovic, Anders M. Dale, Nils Eiel Steen, Ole A. Andreassen · 发表于：American Journal of Psychiatry · 年份：2023 · DOI：10.1176/appi.ajp.20220660 · 被引用次数：69 · 研究领域：Genetic Associations and Epidemiology、Schizophrenia research and treatment、Tryptophan and brain disorders

OBJECTIVE: Schizophrenia is associated with increased risk of cardiovascular disease (CVD), although there is variation in risk among individuals. There are indications of shared genetic etiology between schizophrenia and CVD, but the nature of the overlap remains unclear. The aim of this study was to fill this gap in knowledge. METHODS: Overlapping genetic architectures between schizophrenia and CVD risk factors were assessed by analyzing recent genome-wide association study (GWAS) results. The bivariate causal mixture model (MiXeR) was applied to estimate the number of shared variants and the conjunctional false discovery rate (conjFDR) approach was used to pinpoint specific shared loci. RESULTS: Extensive genetic overlap was found between schizophrenia and CVD risk factors, particularly smoking initiation (N=8.6K variants) and body mass index (BMI) (N=8.1K variants). Several specific shared loci were detected between schizophrenia and BMI (N=304), waist-to-hip ratio (N=193), smoking initiation (N=293), systolic (N=294) and diastolic (N=259) blood pressure, type 2 diabetes (N=147), lipids (N=471), and coronary artery disease (N=35). The schizophrenia risk loci shared with smoking initiation had mainly concordant effect directions, and the risk loci shared with BMI had mainly opposite effect directions. The overlapping loci with lipids, blood pressure, waist-to-hip ratio, type 2 diabetes, and coronary artery disease had mixed effect directions. Functional analyses implicated...