Mendelian Randomization Analyses Suggest Childhood Body Size Indirectly Influences End Points From Across the Cardiovascular Disease Spectrum Through Adult Body Size

Grace M Power*, Jessica Tyrrell, Timothy Frayling, George Davey Smith, Tom G Richardson

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Background: Obesity is associated with long-term health consequences including cardiovascular disease (CVD). Separating the independent effects of childhood and adulthood obesity on CVD risk is challenging as children with obesity typically remain overweight throughout the lifecourse.

Methods and Results: This study used two-sample univariable and multivariable mendelian randomisation (MR) to estimate the effect of childhood body size both independently and after accounting for adult body size on 12 endpoints across the CVD disease spectrum. Univariable analyses identified strong evidence of a total effect between genetically predicted childhood body size and increased risk of atherosclerosis, atrial fibrillation, coronary artery disease, heart failure, hypertension, myocardial infarction, peripheral artery disease and varicose veins. However, evidence of a direct effect was weak after accounting for adult body size using multivariable MR, suggesting that childhood body size indirectly increases risk of these eight disease outcomes via the pathway involving adult body size.

Conclusions: These findings suggest that the effect of genetically predicted childhood body size on the CVD outcomes analysed in this study are a result of larger body size persisting into adulthood. Further research is necessary to ascertain the critical timepoints where the detrimental impact of obesity initiated in early life begins to become immutable.
Original languageEnglish
JournalJournal of the American Heart Association
Volume10
Issue number17
DOIs
Publication statusPublished - 7 Sep 2021

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