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

Abstract 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 g...

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Vydané v:Schizophrenia bulletin Ročník 48; číslo 2; s. 463 - 473
Hlavní autori: Veeneman, Rada R, Vermeulen, Jentien M, Abdellaoui, Abdel, Sanderson, Eleanor, Wootton, Robyn E, Tadros, Rafik, Bezzina, Connie R, Denys, Damiaan, Munafò, Marcus R, Verweij, Karin J H, Treur, Jorien L
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: US Oxford University Press 01.03.2022
Predmet:
Blood pressure
Cardiovascular disease
Cardiovascular Diseases - complications
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - psychology
Correlation of Data
Genetic Testing - methods
Genetic Testing - statistics & numerical data
Heart failure
Heart rate
Humans
Mendelian Randomization Analysis - methods
Mendelian Randomization Analysis - statistics & numerical data
Regular
Schizophrenia
Schizophrenia - diagnosis
Schizophrenia - epidemiology
Schizophrenia - physiopathology
coronary artery disease
QT interval
heart rate variability
early repolarization
dilated cardiomyopathy
causality
ISSN:0586-7614, 1745-1701, 1745-1701
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Shrnutí:Abstract 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.
Bibliografia:ObjectType-Article-1
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ISSN:0586-7614
1745-1701
1745-1701
DOI:10.1093/schbul/sbab132