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Burden of disease variants in participants of the long life family study

ScholarsArchive at Oregon State University

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Title Burden of disease variants in participants of the long life family study
Names Stevenson, Meredith (creator)
Bae, Harold (creator)
Schupf, Nicole (creator)
Andersen, Stacy (creator)
Zhang, Qunyuan (creator)
Perls, Thomas (creator)
Sebastiani, Paola (creator)
Date Issued 2015-02 (iso8601)
Note This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Impact Journals, LLC. The published article can be found at: http://www.ncbi.nlm.nih.gov/pmc/journals/1105/.
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.
Genre Article
Access Condition http://creativecommons.org/licenses/by/3.0/us/
Topic Alzheimer’s disease
Identifier Stevenson, M., Bae, H., Schupf, N., Andersen, S., Zhang, Q., Perls, T., & Sebastiani, P. (2015). Burden of disease variants in participants of the long life family study. Aging, 7(2), 123-132.

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