Whole-Genome Sequencing of a Healthy Aging Cohort.
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. VIDEO ABSTRACT.
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA.
Galina A
GA
Erikson
Inova Translational Medicine Institute, Inova Health System, Falls Church, VA 22042 USA.
Dale L
DL
Bodian
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA.
Manuel
M
Rueda
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA.
Bhuvan
B
Molparia
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA.
Erick R
ER
Scott
Cypher Genomics, Inc., San Diego, CA 92121, USA.
Ashley A
AA
Scott-Van Zeeland
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA.
Sarah E
SE
Topol
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA.
Nathan E
NE
Wineinger
Inova Translational Medicine Institute, Inova Health System, Falls Church, VA 22042 USA; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
John E
JE
Niederhuber
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: etopol@scripps.edu.
Eric J
EJ
Topol
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA; Cypher Genomics, Inc., San Diego, CA 92121, USA. Electronic address: atorkama@scripps.edu.
Ali
A
Torkamani
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics; D000066492:Cognitive Aging; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008136:Longevity; D008297:Male