Dataset Information

Age-specific effects of childhood body mass index on multiple sclerosis risk.

ABSTRACT:

Objective

Higher body mass index (BMI) during early life is thought to be a causal risk factor for multiple sclerosis (MS). We used longitudinal Mendelian randomisation (MR) to determine whether there is a critical window during which BMI influences MS risk.

Methods

Summary statistics for childhood BMI (n ~ 28,000 children) and for MS susceptibility were obtained from recent large genome-wide association studies (GWAS) (n = 14,802 MS, 26,703 controls). We generated exposure instruments for BMI during four non-overlapping age epochs (< 3 months, 3 months-1.5 years, 2-5 years, and 7-8 years) and performed MR using the inverse variance weighted method with standard sensitivity analyses. Multivariable MR was used to account for effects mediated via later-life BMI.

Results

For all age epochs other than birth, genetically determined higher BMI was associated with an increased liability to MS: Birth [Odds Ratio (OR) 0.81, 95% Confidence Interval (CI) 0.50-1.31, Number of Single-Nucleotide Polymorphisms (N_SNPs) = 7, p = 0.39], Infancy (OR 1.18, 95% CI 1.04-1.33, N_SNPs = 18, p = 0.01), Early childhood (OR 1.31, 95% CI 1.03-1.66, N_SNPs = 4, p = 0.03), Later childhood (OR 1.34, 95% CI 1.08-1.66, N_SNPs = 4, p = 0.01). Multivariable MR suggested that these effects may be mediated by effects on adult BMI.

Conclusion

We provide evidence using MR that genetically determined higher BMI during early life is associated with increased MS risk. This effect may be driven by shared genetic architecture with later-life BMI.

SUBMITTER: Hone L

PROVIDER: S-EPMC9363310 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Age-specific effects of childhood body mass index on multiple sclerosis risk.

Hone Luke L Jacobs Benjamin M BM Marshall Charles C Giovannoni Gavin G Noyce Alastair A Dobson Ruth R

Journal of neurology 20220509 9

<h4>Objective</h4>Higher body mass index (BMI) during early life is thought to be a causal risk factor for multiple sclerosis (MS). We used longitudinal Mendelian randomisation (MR) to determine whether there is a critical window during which BMI influences MS risk.<h4>Methods</h4>Summary statistics for childhood BMI (n ~ 28,000 children) and for MS susceptibility were obtained from recent large genome-wide association studies (GWAS) (n = 14,802 MS, 26,703 controls). We generated exposure instru ...[more]

PMID: 35532785

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Project description:BackgroundLittle is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15.Methods and findingsUsing data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N?=?4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL- and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15.ConclusionChanges in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight.

Dataset Information

Age-specific effects of childhood body mass index on multiple sclerosis risk.

Objective

Methods

Results

Conclusion

Publications

Age-specific effects of childhood body mass index on multiple sclerosis risk.

Similar Datasets

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