基础代谢率的性别特异性孟德尔随机化全表型关联研究
Sex-specific Mendelian randomization phenome-wide association study of basal metabolic rate.
作者信息
Ng Jack C M, Schooling C Mary
机构信息
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong Special Administrative Region, China.
Graduate School of Public Health and Health Policy, The City University of New York, 55 West 125th St, New York, NY, 10027, USA.
出版信息
Sci Rep. 2025 Apr 24;15(1):14368. doi: 10.1038/s41598-025-98017-9.
Observationally, higher basal metabolic rate (BMR) is associated with metabolism-related disorders, cancer, aging, and mortality. In this Mendelian randomization (MR) phenome-wide association study, using two-sample MR methods, we systematically and comprehensively investigated the health effects of genetically predicted BMR across the phenome sex-specifically. We obtained sex-specific genetic variants strongly (p < 5 × 10) and independently (r < 0.001) predicting BMR from the UK Biobank and applied them to over 1,000 phenotypes within the same study. We combined genetic variant-specific Wald estimates using inverse-variance weighting, supplemented by sensitivity analysis. We used a false-discovery rate correction to allow for multiple comparisons as well as multivariable MR adjusted for body mass index and testosterone to investigate the independent effects of BMR on phenotypes with significant univariable associations. We obtained 217/219 genetic variants predicting BMR and applied them to 1,150/1,242 phenotypes in men/women, respectively. BMR was associated with 190/270 phenotypes in univariable analysis and 122/123 phenotypes in multivariable analysis in men/women. Examples of robust associations in multivariable analysis included those with neoplasms, diseases of the circulatory system, and growth and reproductive investment. In conclusion, BMR might affect a wide range of health-related outcomes. The underlying mechanisms and interactions between phenotypes warrant further study, as BMR is modifiable.
观察发现,较高的基础代谢率(BMR)与代谢相关疾病、癌症、衰老和死亡率有关。在这项孟德尔随机化(MR)全表型关联研究中,我们使用双样本MR方法,按性别系统性、全面地研究了基因预测的BMR对全表型的健康影响。我们从英国生物银行获取了强烈(p < 5×10)且独立(r < 0.001)预测BMR的性别特异性基因变异,并将其应用于同一研究中的1000多种表型。我们使用逆方差加权合并基因变异特异性Wald估计,并辅以敏感性分析。我们使用错误发现率校正来进行多重比较,并使用调整了体重指数和睾酮的多变量MR来研究BMR对具有显著单变量关联的表型的独立影响。我们分别获得了217/219个预测BMR的基因变异,并将其应用于男性/女性的1150/1242种表型。在单变量分析中,BMR与男性/女性的190/270种表型相关,在多变量分析中与122/123种表型相关。多变量分析中稳健关联的例子包括与肿瘤、循环系统疾病以及生长和生殖投资相关的关联。总之,BMR可能会影响广泛的健康相关结果。由于BMR是可调节的,表型之间的潜在机制和相互作用值得进一步研究。