Causality of Childhood and Adult Body Mass Index on Sick Sinus Syndrome: A Mendelian Randomization Study.

IF 1 Q3 MEDICINE, GENERAL & INTERNAL
Cureus Pub Date : 2025-03-20 eCollection Date: 2025-03-01 DOI:10.7759/cureus.80913
Guanzhen Xu, Zhuang Liu, Ping Hou
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Abstract

Background The relationship between body mass index (BMI) and the risk of sick sinus syndrome (SSS) remains unclear. Clarifying the impact of BMI on SSS at different life stages is essential for advancing precision medicine and implementing effective prevention strategies to reduce the burden of SSS. Methods The causalities of childhood and adult BMI with SSS were investigated by univariate and multivariate Mendelian randomization. Reverse causalities were also explored to improve the accuracy of causality findings. Different sources of exposure data were used for replication analysis, and the effects of sample overlap were investigated using MRlap. The stability of the results was further enhanced through meta-analysis. Results There was a positive correlation of adult BMI with the risk of SSS in both the FinnGen (odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.01-1.35, P = 0.031) and Integrative Epidemiology Unit (IEU) open genome-wide association study (GWAS) project (OR = 1.18, 95% CI 1.04-1.34, P = 0.009) databases. The causality remained valid after the correction of telomere length. There was no causality detected between childhood BMI and SSS, as determined by independent studies of the Early Growth Genetics (EGG) 2020 (OR = 1.06, 95% CI 0.89-1.27, P = 0.513) and EGG2015 (OR = 1.02, 95% CI 0.97-1.09, P = 0.423). Meta-analysis results further confirmed the reliability of the causal inference. Conclusions The findings indicate that elevated BMI in adults, particularly among middle-aged and elderly populations, increases the risk of developing SSS. In contrast, no causal relationship was observed between childhood BMI and SSS, suggesting that the influence of BMI on SSS susceptibility may predominantly emerge during later life stages. These results highlight the need for targeted public health interventions to address adult obesity as a modifiable risk factor for SSS.

背景 身体质量指数(BMI)与病窦综合征(SSS)风险之间的关系仍不清楚。明确 BMI 在不同生命阶段对 SSS 的影响对于推进精准医疗和实施有效的预防策略以减轻 SSS 的负担至关重要。方法 通过单变量和多变量孟德尔随机法研究了儿童和成人 BMI 与 SSS 的因果关系。此外,还探讨了反向因果关系,以提高因果关系研究结果的准确性。重复分析中使用了不同来源的暴露数据,并使用 MRlap 调查了样本重叠的影响。通过元分析进一步提高了结果的稳定性。结果 在FinnGen(比值比(OR)=1.17,95% 置信区间(CI)1.01-1.35,P = 0.031)和Integrative Epidemiology Unit(IEU)开放式全基因组关联研究(GWAS)项目(OR = 1.18,95% CI 1.04-1.34,P = 0.009)数据库中,成人体重指数与罹患SSS的风险呈正相关。端粒长度校正后,因果关系仍然有效。早期生长遗传学(EGG)2020(OR = 1.06,95% CI 0.89-1.27,P = 0.513)和 EGG2015(OR = 1.02,95% CI 0.97-1.09,P = 0.423)的独立研究确定,儿童 BMI 与 SSS 之间没有因果关系。元分析结果进一步证实了因果推论的可靠性。结论 研究结果表明,成年人,尤其是中老年人群的体重指数升高会增加罹患 SSS 的风险。相比之下,儿童时期的体重指数与 SSS 之间没有因果关系,这表明体重指数对 SSS 易感性的影响可能主要出现在生命的晚期阶段。这些结果突出表明,有必要采取有针对性的公共卫生干预措施,以解决成人肥胖这一可改变的 SSS 风险因素。
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