title: Associations of triglyceride levels with longevity and frailty: A Mendelian randomization analysis.
abstract: Observational studies suggest associations of triglyceride levels with longevity and frailty. This study aimed to test whether the associations are causal. We used data from the Rugao Longevity and Ageing Study, a population-based cohort study performed in Rugao, China. A variant in the APOA5 gene region (rs662799) was used as the genetic instrument. Mendelian randomization (MR) analyses were performed to examine the associations of genetically predicted triglycerides with two ageing phenotypes - longevity ( ≥95 years) and frailty (modified Fried frailty phenotype and Rockwood frailty index). C allele of rs662799 was robustly associated with higher triglyceride levels in the comparison group (β = 0.301 mmol/L per allele, p < 0.001), with an F statistic of 95.3 and R2= 0.040. However MR analysis did not provide strong evidence for an association between genetically predicted triglyceride levels and probability of longevity (OR: 0.61; 95% CI: 0.35, 1.07 per 1 mmol/L increase in triglycerides). In the ageing arm (70-84 years), genetically predicted triglyceride levels were not associated with the frailty index (β = 0.008; 95% CI: -0.013, 0.029) or the frailty phenotype (OR: 1.91; 95% CI: 0.84, 4.37). In conclusion, there is currently a lack of sufficient evidence to support causal associations of triglyceride levels with longevity and frailty in elderly populations.
authors.affiliation: Unit of epidemiology, State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, 200433, Shanghai, China.
authors.forename: Zuyun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Burgess
authors.affiliation: Rugao People's Hospital, Rugao 226500 Jiangsu, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Unit of epidemiology, State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, 200433, Shanghai, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Deng
authors.affiliation: Rugao People's Hospital, Rugao 226500 Jiangsu, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Chu
authors.affiliation: Department of Neurology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.affiliation: Rugao People's Hospital, Rugao 226500 Jiangsu, China.
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Rugao People's Hospital, Rugao 226500 Jiangsu, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Shi
authors.affiliation: Rugao People's Hospital, Rugao 226500 Jiangsu, China.
authors.forename: Xuejuan
authors.initials: X
authors.lastname: Xie
authors.affiliation: Rugao People's Hospital, Rugao 226500 Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Unit of epidemiology, State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, 200433, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Unit of epidemiology, State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, 200433, Shanghai, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang