title: Burden of disease variants in participants of the Long Life Family Study.
abstract: 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.
authors: Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
authors: Meredith
authors: M
authors: Stevenson
authors: College of Public Health and Human Sciences, Oregon State University, OR 97331, USA.
authors: Harold
authors: H
authors: Bae
authors: Department of Neurology, Columbia UNiversity, New York City, NY 10027, USA.
authors: Nicole
authors: N
authors: Schupf
authors: Section of Geriatrics, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118, USA.
authors: Stacy
authors: S
authors: Andersen
authors: Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors: Qunyuan
authors: Q
authors: Zhang
authors: Section of Geriatrics, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118, USA.
authors: Thomas
authors: T
authors: Perls
authors: Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
authors: Paola
authors: P
authors: Sebastiani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment