Exploring the Relationship Between Schizophrenia and Cardiovascular Disease: A Genetic Correlation and Multivariable Mendelian Randomization Study

被引:37
|
作者
Veeneman, Rada R. [1 ]
Vermeulen, Jentien M. [1 ]
Abdellaoui, Abdel [1 ]
Sanderson, Eleanor [2 ,3 ]
Wootton, Robyn E. [2 ,4 ]
Tadros, Rafik [5 ,6 ]
Bezzina, Connie R. [6 ]
Denys, Damiaan [1 ]
Munafo, Marcus R. [2 ,7 ]
Verweij, Karin J. H. [1 ]
Treur, Jorien L. [1 ]
机构
[1] Univ Amsterdam, Dept Psychiat, Amsterdam UMC, Amsterdam, Netherlands
[2] Univ Bristol, Integrat Epidemiol Unit, Bristol, Avon, England
[3] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England
[4] Lovisenberg Diaconal Hosp, Nic Waals Inst, Oslo, Norway
[5] Univ Montreal, Fac Med, Cardiovasc Genet Ctr, Montreal Heart Inst, Montreal, PQ, Canada
[6] Univ Amsterdam, Heart Ctr, Dept Expt Cardiol, Amsterdam UMC,Amsterdam Cardiovasc Sci, Amsterdam, Netherlands
[7] Univ Bristol, Sch Psychol Sci, Tobacco & Alcohol Res Grp, Bristol, Avon, England
关键词
coronary artery disease; heart rate variability; QT interval; early repolarization; dilated cardiomyopathy; causality; HEART-RATE-VARIABILITY; METABOLIC SYNDROME; BIPOLAR DISORDER; EARLY REPOLARIZATION; MENTAL-ILLNESS; ASSOCIATION; PREVALENCE; RISK; METAANALYSIS; SMOKING;
D O I
10.1093/schbul/sbab132
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to unravel the nature of this relationship. We obtained summary-data of genome-wide-association studies of schizophrenia (N = 130 644), heart failure (N = 977 323), coronary artery disease (N = 332 477), systolic and diastolic blood pressure (N = 757 601), heart rate variability (N = 46 952), QT interval (N = 103 331), early repolarization and dilated cardiomyopathy ECG patterns (N = 63 700). We computed genetic correlations and conducted bi-directional Mendelian randomization (MR) to assess causality. With multivariable MR, we investigated whether causal effects were mediated by smoking, body mass index, physical activity, lipid levels, or type 2 diabetes. Genetic correlations between schizophrenia and CVD were close to zero (-0.02-0.04). There was evidence that liability to schizophrenia causally increases heart failure risk. This effect remained consistent with multivariable MR. There was also evidence that liability to schizophrenia increases early repolarization pattern, largely mediated by BMI and lipids. Finally, there was evidence that liability to schizophrenia increases heart rate variability, a direction of effect contrasting clinical studies. There was weak evidence that higher systolic blood pressure increases schizophrenia risk. Our finding that liability to schizophrenia increases heart failure is consistent with the notion that schizophrenia involves a systemic dysregulation of the body with detrimental effects on the heart. To decrease cardiovascular mortality among individuals with schizophrenia, priority should lie with optimal treatment in early stages of psychosis.
引用
收藏
页码:463 / 473
页数:11
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