Genetic predisposition to smoking in relation to 14 cardiovascular diseases - PubMed (original) (raw)

Genetic predisposition to smoking in relation to 14 cardiovascular diseases

Susanna C Larsson et al. Eur Heart J. 2020.

Abstract

Aims: 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.

Keywords: Cardiovascular disease; Lifestyle; Mendelian randomization; Risk factors; Single-nucleotide polymorphisms; Smoking.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

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Figures

Figure 1

Figure 1

Summary of data sources and methods used in this study. AF, atrial fibrillation; AFGen, Atrial Fibrillation Consortium; CAD, coronary artery disease; CVD, cardiovascular disease; IVW, inverse-variance weighted; MR, Mendelian randomization; MVP, Million Veteran Program; SNP, single-nucleotide polymorphism; VTE, venous thromboembolism. aData extracted were beta coefficients with corresponding standard errors of the SNP–smoking and SNP–CVD associations.

Figure 2

Figure 2

Associations of genetic predisposition to smoking initiation with 14 cardiovascular diseases in UK Biobank. The odds ratios correspond to the increase of one standard deviation in prevalence of smoking initiation (ever smoked regularly). Estimates are from the multiplicative random-effects inverse variance-weighted method. CI, confidence interval; OR, odds ratio. The I 2 statistic quantifies the amount of heterogeneity among estimates based on individual SNPs. a Significant at the Bonferroni-corrected threshold of P <3.6 × 10−3.

Figure 3

Figure 3

Associations of genetically predicted lifetime smoking index with 14 cardiovascular diseases in UK Biobank. Odds ratios are expressed per one standard deviation increase of the lifetime smoking index. Estimates are from the multiplicative random-effects inverse variance-weighted method. CI, confidence interval; OR, odds ratio. The I 2 statistic quantifies the amount of heterogeneity among estimates based on individual SNPs individual SNPs. aSignificant at the Bonferroni-corrected threshold of P <3.6 × 10−3.

Take home figure

Take home figure

Observed associations of genetic predisposition to smoking initiation and lifetime smoking with cardiovascular diseases in UK Biobank. aNo robust association was observed between smoking and venous thromboembolism (pulmonary embolism and deep vein thrombosis combined) in the Million Veteran Program.

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