TY - JOUR
T1 - Whole-Genome Sequencing of a Healthy Aging Cohort
AU - Erikson, Galina A.
AU - Bodian, Dale L.
AU - Rueda, Manuel
AU - Molparia, Bhuvan
AU - Scott, Erick R.
AU - Scott-Van Zeeland, Ashley A.
AU - Topol, Sarah E.
AU - Wineinger, Nathan E.
AU - Niederhuber, John E.
AU - Topol, Eric J.
AU - Torkamani, Ali
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/5/5
Y1 - 2016/5/5
N2 - Studies of long-lived individuals have revealed few genetic mechanisms for protection against age-associated disease. Therefore, we pursued genome sequencing of a related phenotype - healthy aging - to understand the genetics of disease-free aging without medical intervention. In contrast with studies of exceptional longevity, usually focused on centenarians, healthy aging is not associated with known longevity variants, but is associated with reduced genetic susceptibility to Alzheimer and coronary artery disease. Additionally, healthy aging is not associated with a decreased rate of rare pathogenic variants, potentially indicating the presence of disease-resistance factors. In keeping with this possibility, we identify suggestive common and rare variant genetic associations implying that protection against cognitive decline is a genetic component of healthy aging. These findings, based on a relatively small cohort, require independent replication. Overall, our results suggest healthy aging is an overlapping but distinct phenotype from exceptional longevity that may be enriched with disease-protective genetic factors.
AB - Studies of long-lived individuals have revealed few genetic mechanisms for protection against age-associated disease. Therefore, we pursued genome sequencing of a related phenotype - healthy aging - to understand the genetics of disease-free aging without medical intervention. In contrast with studies of exceptional longevity, usually focused on centenarians, healthy aging is not associated with known longevity variants, but is associated with reduced genetic susceptibility to Alzheimer and coronary artery disease. Additionally, healthy aging is not associated with a decreased rate of rare pathogenic variants, potentially indicating the presence of disease-resistance factors. In keeping with this possibility, we identify suggestive common and rare variant genetic associations implying that protection against cognitive decline is a genetic component of healthy aging. These findings, based on a relatively small cohort, require independent replication. Overall, our results suggest healthy aging is an overlapping but distinct phenotype from exceptional longevity that may be enriched with disease-protective genetic factors.
UR - http://www.scopus.com/inward/record.url?scp=84963958046&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2016.03.022
DO - 10.1016/j.cell.2016.03.022
M3 - Article
C2 - 27114037
AN - SCOPUS:84963958046
SN - 0092-8674
VL - 165
SP - 1002
EP - 1011
JO - Cell
JF - Cell
IS - 4
ER -