Open Access

Genetic predisposition to smoking in relation to 14 cardiovascular diseases

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Date: 16 April 2020
Journal: European Heart Journal , Volume 41 , Issue 35 , Pages 3304 - 3310
Topic: ARRHYTHMIAS AND DEVICE THERAPY, CORONARY ARTERY DISEASE, ACUTE CORONARY SYNDROMES, ACUTE CARDIAC CARE, Acute Coronary Syndromes, DISEASES OF THE AORTA, PERIPHERAL VASCULAR DISEASE, STROKE, Arrhythmias, General, Diseases of the Aorta, Peripheral Vascular and Cerebrovascular Disease, Stroke, HEART FAILURE, Chronic Heart Failure, PREVENTIVE CARDIOLOGY, Risk Factors and Prevention, VALVULAR, MYOCARDIAL, PERICARDIAL, PULMONARY, CONGENITAL HEART DISEASE, Pericardial Disease, Pulmonary Circulation, Pulmonary Embolism, Right Heart Failure, BASIC SCIENCE
Authors: S. Larsson , A. Mason , M. Bäck , D. Klarin , S. Damrauer , . , K. Michaëlsson , S. Burgess

ESC Journals

AbstractAims

The aim of this study was to use Mendelian randomization (MR) to determine the causality of the association between smoking and 14 different cardiovascular diseases (CVDs).

Methods and results

Our primary genetic instrument comprised 361 single-nucleotide polymorphisms (SNPs) associated with smoking initiation (ever smoked regularly) at genome-wide significance. Data on the associations between the SNPs and 14 CVDs were obtained from the UK Biobank study (N = 367 643 individuals), CARDIoGRAMplusC4D consortium (N = 184 305 individuals), Atrial Fibrillation Consortium (2017 dataset; N = 154 432 individuals), and Million Veteran Program (MVP; N = 190 266 individuals). The main analyses were conducted using the random-effects inverse-variance weighted method and complemented with multivariable MR analyses and the weighted median and MR-Egger approaches. Genetic predisposition to smoking initiation was most strongly and consistently associated with higher odds of coronary artery disease, heart failure, abdominal aortic aneurysm, ischaemic stroke, transient ischaemic attack, peripheral arterial disease, and arterial hypertension. Genetic predisposition to smoking initiation was additionally associated with higher odds of deep vein thrombosis and pulmonary embolism in the UK Biobank but not with venous thromboembolism in the MVP. There was limited evidence of causal associations of smoking initiation with atrial fibrillation, aortic valve stenosis, thoracic aortic aneurysm, and intracerebral and subarachnoid haemorrhage.

Conclusion

This MR study supports a causal association between smoking and a broad range of CVDs, in particular, coronary artery disease, heart failure, abdominal aortic aneurysm, ischaemic stroke, transient ischaemic attack, peripheral arterial disease, and arterial hypertension.

About the contributors

Susanna C Larsson

Role: Author

Amy M Mason

Role: Author

Magnus Bäck

Role: Author