Whole-Genome Sequencing of a Healthy Aging Cohort

被引：148

作者：

Erikson, Galina A. ^{[1
,2
]}

Bodian, Dale L. ^{[3
]}

Rueda, Manuel ^{[1
,2
]}

Molparia, Bhuvan ^{[1
,2
]}

Scott, Erick R. ^{[1
,2
]}

Scott-Van Zeeland, Ashley A. ^{[5
]}

Topol, Sarah E. ^{[1
,2
]}

Wineinger, Nathan E. ^{[1
,2
]}

Niederhuber, John E. ^{[3
,4
]}

Topol, Eric J. ^{[1
,2
]}

Torkamani, Ali ^{[1
,2
,5
]}

机构：

[1] Scripps Hlth, Scripps Translat Sci Inst, La Jolla, CA 92037 USA

[2] Scripps Res Inst, La Jolla, CA 92037 USA

[3] Inova Hlth Syst, Inova Translat Med Inst, Falls Church, VA 22042 USA

[4] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[5] Cypher Genom Inc, San Diego, CA 92121 USA

来源：

CELL | 2016年 / 165卷 / 04期

关键词：

COMMON GENETIC-VARIATION; WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CLAC BINDS; VARIANTS; METAANALYSIS; LONGEVITY; MORTALITY; ANCESTRY; PROTEIN;

D O I：

10.1016/j.cell.2016.03.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1002 / 1011

页数：10

共 58 条

[1] A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer [J].

Al-Tassan, Nada A. ;

Whiffin, Nicola ;

Hosking, Fay J. ;

Palles, Claire ;

Farrington, Susan M. ;

Dobbins, Sara E. ;

Harris, Rebecca ;

Gorman, Maggie ;

Tenesa, Albert ;

Meyer, Brian F. ;

Wakil, Salma M. ;

Kinnersley, Ben ;

Campbell, Harry ;

Martin, Lynn ;

Smith, Christopher G. ;

Idziaszczyk, Shelley ;

Barclay, Ella ;

Maughan, Timothy S. ;

Kaplan, Richard ;

Kerr, Rachel ;

Kerr, David ;

Buchannan, Daniel D. ;

Win, Aung Ko ;

Hopper, John ;

Jenkins, Mark ;

Lindor, Noralane M. ;

Newcomb, Polly A. ;

Gallinger, Steve ;

Conti, David ;

Schumacher, Fred ;

Casey, Graham ;

Dunlop, Malcolm G. ;

Tomlinson, Ian P. ;

Cheadle, Jeremy P. ;

Houlston, Richard S. .

SCIENTIFIC REPORTS, 2015, 5

[2] Enhancements to the ADMIXTURE algorithm for individual ancestry estimation [J].

Alexander, David H. ;

Lange, Kenneth .

BMC BIOINFORMATICS, 2011, 12

[3]

[Anonymous], 120 SOC SEC ACT

[4] Lipoprotein genotype and conserved pathway for exceptional longevity in humans [J].

Atzmon, G ;

Rincon, M ;

Schechter, CB ;

Shuldiner, AR ;

Lipton, RB ;

Bergman, A ;

Barzilai, N .

PLOS BIOLOGY, 2006, 4 (04) :562-569

[5] Genome-wide association study (GWAS)-identified disease risk alleles do not compromise human longevity [J].

Beekman, Marian ;

Nederstigt, Christa ;

Suchiman, H. Eka D. ;

Kremer, Dennis ;

van der Breggen, Ruud ;

Lakenberg, Nico ;

Alemayehu, Wendimagegn Ghidey ;

de Craen, Anton J. M. ;

Westendorp, Rudi G. J. ;

Boomsma, Dorret I. ;

de Geus, Eco J. C. ;

Houwing-Duistermaat, Jeanine J. ;

Heijmans, Bastiaan T. ;

Slagboom, P. Eline .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (42) :18046-18049

[6] Germline Variation in Cancer-Susceptibility Genes in a Healthy, Ancestrally Diverse Cohort: Implications for Individual Genome Sequencing [J].

Bodian, Dale L. ;

McCutcheon, Justine N. ;

Kothiyal, Prachi ;

Huddleston, Kathi C. ;

Iyer, Ramaswamy K. ;

Vockley, Joseph G. ;

Niederhuber, John E. .

PLOS ONE, 2014, 9 (04)

[7] The common germline Arg72Pro polymorphism of p53 and increased longevity in humans [J].

Bojesen, Stig E. ;

Nordestgaard, Borge G. .

CELL CYCLE, 2008, 7 (02) :158-163

[8] Genetics of healthy aging and longevity [J].

Brooks-Wilson, Angela R. .

HUMAN GENETICS, 2013, 132 (12) :1323-1338

[9] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[10] The quest for genetic determinants of human longevity: challenges and insights [J].

Christensen, Kaare ;

Johnson, Thomas E. ;

Vaupel, James W. .

NATURE REVIEWS GENETICS, 2006, 7 (06) :436-448

← 1 2 3 4 5 6 →