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

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

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Vydáno v:Journal of the American Heart Association Ročník 10; číslo 17; s. e021503
Hlavní autoři: Power, Grace M., Tyrrell, Jessica, Frayling, Timothy M., Davey Smith, George, Richardson, Tom G.
Médium: Journal Article
Jazyk:angličtina
Vydáno: England John Wiley and Sons Inc 07.09.2021
Wiley
Témata:
Adult
Body Size
cardiovascular disease
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - genetics
Child
genetic epidemiology
Humans
lifecourse
Mendelian randomization
Mendelian Randomization Analysis
obesity
Obesity - epidemiology
Obesity - genetics
Original Research
Risk Factors
cardiovascular disease
lifecourse
Mendelian randomization
obesity
genetic epidemiology
ISSN:2047-9980, 2047-9980
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Shrnutí:Background Obesity is associated with long-term health consequences including cardiovascular disease. Separating the independent effects of childhood and adulthood obesity on cardiovascular disease risk is challenging as children with obesity typically remain overweight throughout the lifecourse. Methods and Results This study used 2-sample univariable and multivariable Mendelian randomization to estimate the effect of childhood body size both independently and after accounting for adult body size on 12 endpoints across the cardiovascular disease 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 Mendelian randomization, suggesting that childhood body size indirectly increases risk of these 8 disease outcomes via the pathway involving adult body size. Conclusions These findings suggest that the effect of genetically predicted childhood body size on the cardiovascular disease outcomes analyzed in this study are a result of larger body size persisting into adulthood. Further research is necessary to ascertain the critical timepoints where, if ever, the detrimental impact of obesity initiated in early life begins to become immutable.
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For Sources of Funding and Disclosures, see page 7.
Supplementary Material for this article is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.121.021503
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.121.021503