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.
Highlights
Longevity implies exceptional survival and has been considered as a rare but important aging phenotype[1]
C allele of rs662799 was robustly associated with higher triglyceride levels (beta coefficient (β) = 0.301 mmol/L per allele, p < 0.001), with an F statistic of 95.3 and R2 = 0.040
The specific study design in Rugao Longevity and Ageing Study (RuLAS) provides us with the unique ability to simultaneously examine determinants of longevity and ageing[9,10]
Summary
Longevity implies exceptional survival and has been considered as a rare but important aging phenotype[1]. Observational studies have suggested associations of triglyceride levels with longevity and frailty[5,6] Common limitations such as potential confounding or reverse causation have made it difficult for observational studies to identify the causal roles of biomarkers in the pathological process of an outcome[7]. In this context, based on the random assignment of genotype from parents that occurs before conception, the Mendelian randomization (MR) approach has been proposed to strengthen causal inferences using genetic variants associated with an exposure (e.g., biomarker) as instrumental variables (e.g., unrelated to potential confounding factors)[7]. The aforementioned genetic variant rs662799 was used as the genetic instrument
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
