Jiesisibieke Zhu Liduzi, Chan Io Ieong, Ng Jack Chun Man, Schooling C Mary
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao, China.
Elife. 2025 Jun 11;13:RP102573. doi: 10.7554/eLife.102573.
Trials of incretins are making it increasingly clear that body mass index (BMI) is linked to several diseases throughout life, but trials cannot easily provide a comprehensive assessment of the role of BMI in health-related attributes for men and women. To systematically investigate the role of BMI, we conducted a sex-specific Mendelian randomization-phenome-wide association study.
We comprehensively examined the associations of genetically predicted BMI in women (: 194,174) and men (: 167,020) using health-related attributes from the UK Biobank with inverse variance weighting and sensitivity analysis.
BMI impacted 232 of 776 traits considered in women and 203 of 680 traits in men, after adjusting for false discovery; differences by sex were found for 105 traits, and 46 traits remained after adjusting for false discovery. BMI was more strongly positively associated with myocardial infarction, major coronary heart disease events, ischemic heart disease, and heart attack in men than women. BMI was more strongly positively associated with apolipoprotein B (ApoB) and diastolic blood pressure in women than men.
Our study revealed that BMI might affect a wide range of health-related attributes and also highlights notable sex differences in its impact, including opposite associations for certain attributes, such as ApoB; and stronger effects in men, such as for cardiovascular diseases. Our findings underscore the need for nuanced, sex-specific policy related to BMI to address inequities in health.
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肠促胰岛素试验越来越清楚地表明，体重指数（BMI）与一生中的多种疾病相关，但试验难以轻易全面评估BMI在男性和女性健康相关特征中的作用。为了系统地研究BMI的作用，我们进行了一项性别特异性的孟德尔随机化-全表型关联研究。
我们使用英国生物银行中与健康相关的特征，通过逆方差加权和敏感性分析，全面研究了女性（n = 194,174）和男性（n = 167,020）中基因预测BMI的关联。
在调整错误发现率后，BMI影响了女性所考虑的776个性状中的232个，男性所考虑的680个性状中的203个；发现105个性状存在性别差异，调整错误发现率后有46个性状仍然存在差异。与女性相比，BMI在男性中与心肌梗死、主要冠心病事件、缺血性心脏病和心脏病发作的正相关性更强。与男性相比，BMI在女性中与载脂蛋白B（ApoB）和舒张压的正相关性更强。
我们的研究表明，BMI可能影响广泛的健康相关特征，并且还突出了其影响中显著的性别差异，包括某些特征的相反关联，如ApoB；以及在男性中的更强影响，如对心血管疾病的影响。我们的发现强调了需要制定与BMI相关的细致、针对性别的政策，以解决健康方面的不平等问题。
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