体重指数、遗传易感性与阿尔茨海默病：基于英国生物库 475813 名参与者的纵向研究。
Body mass index, genetic susceptibility, and Alzheimer's disease: a longitudinal study based on 475,813 participants from the UK Biobank.
机构信息
Department of Neurology, The First Affiliated Hospital of Jinan University, No. 613, Huangpu Road West, Guangzhou, 510630, Guangdong, China.
School of Public Health, Jiaotong University Health Science Center, Shaanxi Province, Xi'an, 710061, China.
出版信息
J Transl Med. 2022 Sep 9;20(1):417. doi: 10.1186/s12967-022-03621-2.
BACKGROUND
The association between body mass index (BMI) and Alzheimer's disease (AD) remains controversial. Genetic and environmental factors are now considered contributors to AD risk. However, little is known about the potential interaction between genetic risk and BMI on AD risk.
OBJECTIVE
To study the causal relationship between BMI and AD, and the potential interaction between AD genetic risk and BMI on AD risk.
METHODS AND RESULTS
Using the UK Biobank database, 475,813 participants were selected for an average follow-up time of more than 10 years.
MAIN FINDINGS
- there was a nonlinear relationship between BMI and AD risk in participants aged 60 years or older (p for non-linear < 0.001), but not in participants aged 37-59 years (p for non-linear = 0.717) using restricted cubic splines; 2) for participants aged 60 years and older, compared with the BMI (23-30 kg/m) group, the BMI (< 23 kg/m) group was associated with a higher AD risk (HR = 1.585; 95% CI 1.304-1.928, p < 0.001) and the BMI (> 30 kg/m) group was associated with a lower AD risk (HR = 0.741; 95% CI 0.618-0.888, p < 0.01) analyzed using the Cox proportional risk model; 3) participants with a combination of high AD genetic risk score (AD-GRS) and BMI (< 23 kg/m) were associated with the highest AD risk (HR = 3.034; 95% CI 2.057-4.477, p < 0.001). In addition, compared with the BMI (< 23 kg/m), the higher BMI was associated with a lower risk of AD in participants with the same intermediate or high AD-GRS; 4) there was a reverse causality between BMI and AD when analyzed using bidirectional Mendelian randomization (MR).
CONCLUSION
There was a reverse causality between BMI and AD analyzed using MR. For participants aged 60 years and older, the higher BMI was associated with a lower risk of AD in participants with the same intermediate or high AD genetic risk. BMI (23-30 kg/m) may be a potential intervention for AD.
背景
体重指数（BMI）与阿尔茨海默病（AD）之间的关联仍存在争议。遗传和环境因素现在被认为是 AD 风险的促成因素。然而，对于遗传风险和 BMI 对 AD 风险的潜在相互作用知之甚少。
目的
研究 BMI 与 AD 之间的因果关系，以及 AD 遗传风险与 BMI 对 AD 风险的潜在相互作用。
方法和结果
使用英国生物库数据库，选择了 475813 名参与者进行平均随访时间超过 10 年。
主要发现
1）使用限制立方样条，参与者年龄在 60 岁或以上时 BMI 与 AD 风险之间存在非线性关系（p 非线性<0.001），但参与者年龄在 37-59 岁时无此关系（p 非线性=0.717）；2）对于 60 岁及以上的参与者，与 BMI（23-30kg/m）组相比，BMI（<23kg/m）组与较高的 AD 风险相关（HR=1.585；95%CI 1.304-1.928，p<0.001），而 BMI（>30kg/m）组与较低的 AD 风险相关（HR=0.741；95%CI 0.618-0.888，p<0.01），使用 Cox 比例风险模型进行分析；3）高 AD 遗传风险评分（AD-GRS）和 BMI（<23kg/m）相结合的参与者与最高 AD 风险相关（HR=3.034；95%CI 2.057-4.477，p<0.001）。此外，与 BMI（<23kg/m）相比，在具有相同中等到高 AD-GRS 的参与者中，更高的 BMI 与 AD 风险较低相关；4）使用双向 Mendelian 随机化（MR）分析时，BMI 与 AD 之间存在反向因果关系。
结论
使用 MR 分析时，BMI 与 AD 之间存在反向因果关系。对于 60 岁及以上的参与者，在具有相同中等到高 AD 遗传风险的参与者中，较高的 BMI 与 AD 风险较低相关。BMI（23-30kg/m）可能是 AD 的潜在干预措施。
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