Dataset Information

Genetically Determined Birthweight Associates With Atrial Fibrillation: A Mendelian Randomization Study.

ABSTRACT:

Background

Atrial fibrillation is a common cardiovascular disorder, characterized by irregular electrical activity in the upper chambers of the heart. Both chronic cardiometabolic risk factors and genetics have been shown to contribute to the development of atrial fibrillation. Birthweight has also been associated with risk of atrial fibrillation.

Methods

In the current study, we utilized a genetic approach to study the effect of birthweight on atrial fibrillation. We used 2-sample Mendelian randomization to consider the impact of birthweight on incident atrial fibrillation using summary data from the Early Growth Genetics Consortium GWAS of birthweight and a large biobank-based GWAS of atrial fibrillation.

Results

Using the framework of 2-sample Mendelian randomization, we found that a 1-SD genetic elevation of birthweight was associated with increased risk of atrial fibrillation (odds ratio, 1.27 [95% CI, 1.14-1.41]; P=1×10^-5) with sensitivity analyses demonstrating robustness of this result.

Conclusions

Our findings clarify the directionality of the relationship between birthweight and atrial fibrillation, supporting the growing body of evidence that intrauterine growth has a lifelong impact on cardiovascular health.

SUBMITTER: Kember RL

PROVIDER: S-EPMC7299774 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Genetically Determined Birthweight Associates With Atrial Fibrillation: A Mendelian Randomization Study.

Kember Rachel L RL Levin Michael G MG Cousminer Diana L DL Tsao Noah N Judy Renae R Schur Gayatri M GM Lubitz Steven A SA Ellinor Patrick T PT McCormack Shana E SE Grant Struan F A SFA Rader Daniel J DJ Voight Benjamin F BF Damrauer Scott M SM

Circulation. Genomic and precision medicine 20200427 3

<h4>Background</h4>Atrial fibrillation is a common cardiovascular disorder, characterized by irregular electrical activity in the upper chambers of the heart. Both chronic cardiometabolic risk factors and genetics have been shown to contribute to the development of atrial fibrillation. Birthweight has also been associated with risk of atrial fibrillation.<h4>Methods</h4>In the current study, we utilized a genetic approach to study the effect of birthweight on atrial fibrillation. We used 2-sampl ...[more]

PMID: 32340472

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Project description:BackgroundPrevious observational studies have documented an inverse association of birthweight with myocardial infarction (MI) but a positive association with atrial fibrillation (AF). However, the causality of these associations and the underlying mediating pathways remain unclear. We aimed to investigate the causal effects of birthweight, incorporating both fetal and maternal genetic effects, on MI and AF, and identify potential mediators in their respective pathways.MethodsWe performed Mendelian randomization (MR) analyses using genome-wide association study summary statistics for birthweight (N = 297,356 for own birthweight and 210,248 for offspring birthweight), MI (Ncase=61,000, Ncontrol=577,000), AF (Ncase=60,620, Ncontrol=970,216), and 52 candidate mediators (N = 13,848-1,295,946). Two-step MR was employed to identify and assess the mediation proportion of potential mediators in the associations of birthweight with MI and AF, respectively. As a complement, we replicated analyses for fetal-specific birthweight and maternal-specific birthweight.ResultsGenetically determined each 1-SD lower birthweight was associated with a 40% (95% CI: 1.22-1.60) higher risk of MI, whereas each 1-SD higher birthweight was causally associated with a 29% (95% CI: 1.16-1.44) higher risk of AF. Cardiometabolic factors, including lipids and lipoproteins, glucose and insulin, blood pressure, and fatty acids, each mediated 4.09-23.71% of the total effect of birthweight on MI, followed by body composition and strength traits (i.e., appendicular lean mass, height, and grip strength) and socioeconomic indicators (i.e., education and household income), with the mediation proportion for each factor ranging from 8.08 to 16.80%. By contrast, appendicular lean mass, height, waist circumference, childhood obesity, and body mass index each mediated 15.03-45.12% of the total effect of birthweight on AF. Both fetal-specific birthweight and maternal-specific birthweight were inversely associated with MI, while only fetal-specific birthweight was positively associated with AF. Psychological well-being and lifestyle factors conferred no mediating effect in either association.ConclusionsCardiometabolic factors mainly mediated the association between lower birthweight and MI, while body composition and strength traits mediated the association between higher birthweight and AF. These findings provide novel evidence for the distinct pathogenesis of MI and AF and advocate adopting a life-course approach to improving fetal development and subsequent causal mediators to mitigate the prevalence and burden of cardiovascular diseases.

Dataset Information

Genetically Determined Birthweight Associates With Atrial Fibrillation: A Mendelian Randomization Study.

Background

Methods

Results

Conclusions

Publications

Genetically Determined Birthweight Associates With Atrial Fibrillation: A Mendelian Randomization Study.

Similar Datasets

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