What is the clinical evidence from this study?

Study design: Observational. Population: Stroke (n=446696). Intervention: Genetically predicted childhood obesity vs. Without childhood obesity. Primary outcome: Risk of stroke (OR 1.04, 95% CI 1.01-1.07, p=0.005).

November 17, 2021Frontiers in Genetics71 citationsOpen Access

Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis

XZXuelun ZouCentral South University SWSai WangHainan University LWLei‐Yun WangCentral South University

Key Result

Genetically predicted childhood obesity was associated with a higher risk of stroke (OR 1.04) and ischemic stroke (OR 1.05), but not intracerebral hemorrhage.

Study Design

Type

Observational (n=446,696)

Structured PICO

Does genetic predisposition to childhood obesity increase the risk of stroke and its subtypes in adults?

Population

13,848 European participants (childhood obesity GWAS) and 446,696 European adults (MEGASTROKE GWAS dataset)

Intervention

Genetic instruments for childhood obesity

Comparator

Absence of genetic instruments for childhood obesity

Outcome

Risk of stroke, intracerebral haemorrhage, ischaemic stroke (IS), and its subtypeshard clinical

Genetic predisposition to childhood obesity is causally associated with a higher risk of stroke, particularly ischaemic and large artery stroke, highlighting the importance of early obesity prevention.

Main Result

Effect estimate: OR 1.04 (95% CI 1.01-1.07)

p-value: p=0.005

Limitations

Only a small number of SNPs were selected as instrumental variables under the standard rules.
Participants were all of European ancestry, limiting generalizability to other ethnic groups.
Features of childhood obesity, such as height and abdominal circumference, were not acquired.
The sample size of GWAS studies in intracerebral hemorrhage is too small, limiting the power to detect causal relationships.

Abstract

Background: The causal relationship between childhood obesity and stroke remains unclear. Our objective was to elucidate the causal relationship between childhood obesity and the risk of stroke and its subtypes by performing Mendelian randomisation (MR) analyses. Methods: Genetic instruments for childhood obesity were obtained from a genome-wide association study (GWAS) of 13,848 European participants. Summary level data for stroke, intracerebral haemorrhage, ischaemic stroke (IS), and its subtypes were evaluated using the MEGASTROKE GWAS dataset, which included 446,696 European adults. Inverse-variance weighting, weighted-median analysis, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), and MR-Robust Adjusted Profile Score were applied in this MR analysis. The leave-one-out sensitivity test, MR-PRESSO Global test, and Cochran’s Q test were conducted to confirm the accuracy and robustness of our results. Results: Genetic evaluations revealed that childhood obesity was associated with a higher risk of stroke (OR = 1.04, 95%CI: 1.01–1.07, p = 0.005) and IS (OR = 1.05, 95%CI: 1.02–1.08, p = 0.003), but not with intracerebral haemorrhage (ICH, OR = 0.93, 95%CI: 0.80–1.09, p = 0.39). In the subtype analysis, childhood obesity was also associated with large artery stroke (LAS, OR = 1.12, 95%CI: 1.02–1.22, p = 0.016) but not with cardioembolic stroke (OR = 1.06, 95%CI: 0.96–1.18, p = 0.21) and small vessel stroke (OR = 1.06, 95%CI: 0.98–1.15, p = 0.17). These results were stable in the sensitivity analysis and remained significant after Bonferroni correction. Conclusion: Our study provides evidence that childhood obesity is associated with a higher risk of stroke, IS, and LAS. The prevention of stroke, especially IS and LAS, should be promoted in populations with childhood obesity.

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