Association between fat mass and mortality: analysis of Mendelian randomization and lifestyle modification

作者全名："Hu, Jinbo; Chen, Xiangjun; Yang, Jun; Giovannucci, Edward; Lee, Dong Hoon; Luo, Wenjin; Cheng, Qingfeng; Gong, Lilin; Wang, Zhihong; Li, Qifu; Yang, Shumin"

作者地址："[Hu, Jinbo; Chen, Xiangjun; Luo, Wenjin; Cheng, Qingfeng; Gong, Lilin; Wang, Zhihong; Li, Qifu; Yang, Shumin] Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 1, Chongqing, Peoples R China; [Hu, Jinbo; Giovannucci, Edward; Lee, Dong Hoon] Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, 665 Huntington Ave, Boston, MA USA; [Yang, Jun] Hudson Inst Med Res, Ctr Endocrinol & Metab, Clayton, Vic, Australia; [Yang, Jun] Monash Univ, Dept Med, Clayton, Vic, Australia; [Li, Qifu; Yang, Shumin] Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi St, Chongqing 400016, Peoples R China"

通信作者："Li, QF; Yang, SM (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi St, Chongqing 400016, Peoples R China."

来源：METABOLISM-CLINICAL AND EXPERIMENTAL

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000878097500006

JCR分区：Q1

影响因子：9.8

年份：2022

卷号：136

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Fat mass; Mortality; Mendelian randomization; Lifestyle modification

摘要："Background: The association between fat mass and mortality has been equivocally shown to be linear, J-shaped, and U-shaped. We aimed to clarify this relationship based on Mendelian randomization (MR) analysis and lifestyle modification.Methods: This prospective analysis included 449,831 participants from UK Biobank. Linear MR analysis was used to estimate the linear relationship between fat mass and mortality. We assessed whole body fat mass by bio-impedance analysis at baseline and categorized subjects into five equal groups based on fat mass index (FMI). The association between FMI and mortality were investigated among whole population and in subgroups stratified by individual lifestyle factors, including diet, physical activity, smoking, alcohol, sleep and psycho-logical health.Findings: Linear MR analyses indicated a positive association between genetically predicted fat mass and all-cause mortality (HR 1.10, 95 % CI 1.08-1.12, P < 0.001). The association between FMI and all-cause mortality was manifested as J-shaped (HRs across FMI categories: 1.04, 1.00, 1.07, 1.21, 1.54), which was significantly modified by the number of low-risk lifestyle factors (P for interaction<0.001). When evaluating individual lifestyle factors, we observed a nonlinear relationship between FMI and all-cause mortality among participants who had high-risk lifestyle factors, while a linear relationship was observed among participants who had low-risk lifestyle factors, especially for those with adequate physical activity (HRs across FMI categories: 0.95, 1.00, 1.05, 1.17, 1.44) and who never smoked (0.96, 1.00, 1.03, 1.14, 1.51).Interpretation: Genetically determined fat mass is causally and linearly associated with mortality. The J-shape association between anthropometric FMI and mortality is caused by high-risk lifestyle factors."

基金机构："National Natural Science Foundation of China; National Natural Science Foundation of China, Major Joint Project [U21A20355]; National Natural Science Foundation of China [81800731, 81870567, 81970720, 82170825]; Joint Medical Research Project of Chongqing Science and Technology Commission & Chongqing Health and Family Planning Commission (Major Project) [2022ZDXM003]; National Key Research & Development Plan of China; Major Project of Prevention and Treatment for Common Diseases [2021YFC2501600, 2021YFC2501603]; Chongqing Outstanding Youth Funds [cstc2019jcyjjq0006]; Program for Youth Innovation in Future Medicine, Chongqing Medical University"

基金资助正文："This work was supported by the National Natural Science Foundation of China, Major Joint Project (U21A20355). The National Natural Science Foundation of China (81800731, 81870567, 81970720, 82170825). Joint Medical Research Project of Chongqing Science and Technology Commission & Chongqing Health and Family Planning Commission (Major Project, 2022ZDXM003). National Key Research & Development Plan of China, Major Project of Prevention and Treatment for Common Diseases (2021YFC2501600, sub-project: 2021YFC2501603). Chongqing Outstanding Youth Funds (cstc2019jcyjjq0006). Program for Youth Innovation in Future Medicine, Chongqing Medical University."