Duan Hongzhe, Arbeev Konstantin, Holmes Rachel, Bagley Olivia, Wu Deqing, Akushevich Igor, Schupf Nicole, Yashin Anatoliy, Ukraintseva Svetlana
Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC, United States.
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, United States.
Front Aging. 2024 Sep 20;5:1442017. doi: 10.3389/fragi.2024.1442017. eCollection 2024.
Overweight, defined by a body mass index (BMI) between 25 and 30, has been associated with enhanced survival among older adults in some studies. However, whether being overweight is causally linked to longevity remains unclear. To investigate this, we conducted a Mendelian randomization (MR) study of lifespan 85+ years, using overweight as an exposure variable and data from the Health and Retirement Study and the Long Life Family Study. An essential aspect of MR involves selecting appropriate single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). This is challenging due to the limited number of SNP candidates within biologically relevant genes that can satisfy all necessary assumptions and criteria. To address this challenge, we employed a novel strategy of creating additional IVs by pairing SNPs between candidate genes. This strategy allowed us to expand the pool of IV candidates with new "composite" SNPs derived from eight candidate obesity genes. Our study found that being overweight between ages 75 and 85, compared to having a normal weight (BMI 18.5-24.9), significantly contributes to improved survival beyond age 85. Results of this MR study thus support a causal relationship between overweight and longevity in older adults.
超重定义为体重指数（BMI）在25至30之间，在一些研究中，超重与老年人存活率提高有关。然而，超重是否与长寿存在因果关系仍不明确。为了对此进行研究，我们利用来自健康与退休研究以及长寿家庭研究的数据，以超重作为暴露变量，对85岁及以上人群的寿命进行了孟德尔随机化（MR）研究。MR的一个关键方面是选择合适的单核苷酸多态性（SNP）作为工具变量（IV）。由于生物学相关基因中能够满足所有必要假设和标准的SNP候选数量有限，这一过程具有挑战性。为应对这一挑战，我们采用了一种新策略，通过将候选基因之间的SNP配对来创建额外的IV。该策略使我们能够利用源自八个候选肥胖基因的新“复合”SNP扩大IV候选池。我们的研究发现，与正常体重（BMI 18.5 - 24.9）相比，75至85岁之间超重显著有助于提高85岁以后的存活率。因此，这项MR研究的结果支持了老年人超重与长寿之间的因果关系。
