Research Paper Volume 7, Issue 2 pp 123—132
Burden of disease variants in participants of the long life family Study
- 1 Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA
- 2 College of Public Health and Human Sciences, Oregon State University, OR 97331, USA
- 3 Department of Neurology, Columbia University, New York City, NY 10027, USA
- 4 Section of Geriatrics, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118, USA
- 5 Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, Campus Box 8506, St. Louis, MO 63108; USA
Received: November 4, 2014 Accepted: February 2, 2015 Published: February 5, 2015https://doi.org/10.18632/aging.100724
How to Cite
Copyright: © 2022 Stevenson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Case control studies of nonagenarians and centenarians provide evidence that long-lived individuals do not differ in the rate of disease associated variants compared to population controls. These results suggest that an enrichment of novel protective variants, rather than a lack of disease associated variants, determine the genetic predisposition to exceptionally long lives. Using data from the Long Life Family Study (LLFS), we sought to replicate these findings and extend them to include a larger number of disease-specific risk alleles. To accomplish this goal, we built a genetic risk score for each of four age-related disease groups: Alzheimer's disease, cardiovascular disease and stroke, type 2 diabetes, and various cancers and compared the distribution of these scores between older participants of the LLFS, their offspring and their spouses. The analyses showed no significant differences in distribution of the genetic risk scores for cardiovascular disease and stroke, type 2 diabetes, or cancer between the groups, while participants of the LLFS appeared to carry an average 1% fewer risk alleles for Alzheimer's disease compared to spousal controls and, while the difference may not be clinically relevant, it was statistically significant. However, the statistical significance between familial longevity and the Alzheimer's disease genetic risk score was lost when a more stringent linkage disequilibrium threshold was imposed to select independent genetic variants.