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How Genes Modulate Patterns of Aging-Related Changes on the Way to 100: Biodemographic Models and Methods in Genetic
Anatoliy I Yashin1, Konstantin G Arbeev2, Deqing Wu3
1Professor, Center for Population Health and Aging, Duke University, 2024 W. Main Street, Room A102E, Durham, NC 27705, USA. Tel.: (+1) 919-668-2713.
North American Actuarial Journal : NAAJ
|October 25, 2016
Summary
Genome-wide association studies (GWAS) for human longevity have been limited. New methods reveal genetic variants influencing lifespan, mediated by physiological changes and biomarkers, aiding longevity research.
Area of Science:
- Genetics
- Gerontology
- Biodemography
Background:
- Genome-wide association studies (GWAS) for human aging and longevity have yielded limited significant and replicable results.
- Challenges include statistical method efficiency, trait heterogeneity, pleiotropic effects, and underestimation of environmental and population-specific factors.
- Longitudinal data potential for understanding genetic mediation of lifespan via physiological variables remains underexplored.
Purpose of the Study:
- To address limitations in current genetic studies of human aging and longevity.
- To investigate genetic regulation of human lifespan using advanced statistical and biodemographic models.
- To explore how genetic variants influence lifespan through physiological variables and biomarkers over time.
Main Methods:
- Performed genome-wide association studies (GWAS) on Framingham Heart Study (FHS) cohort data with varying quality control (QC) procedures.
- Utilized simulation studies to validate data combination approaches for improving GWAS quality.
- Employed stochastic process models and analyzed longitudinal FHS data to assess genetic influences on aging biomarkers and mortality dynamics.
Main Results:
- Different QC procedures yielded distinct sets of genetic variants associated with lifespan.
- Identified 24 genetic variants negatively associated with human lifespan.
- Joint analysis of genetic data and follow-up data significantly improved association strength for 24 SNPs.
- Observed differing aging-related physiological and biomarker trajectories between carriers and non-carriers of selected variants.
Conclusions:
- Biodemographic models and methods enhance genetic association studies for aging and longevity traits.
- Absence of deleterious genetic variants may contribute to exceptional longevity, dynamically mediated by physiological variables and biomarkers.
- Integrative statistical models of mortality risks are beneficial for genetic studies of human aging and longevity.
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