Identification of 12 genetic loci associated with human healthspan

被引:88
|
作者
Zenin, Aleksandr [1 ]
Tsepilov, Yakov [2 ,3 ]
Sharapov, Sodbo [2 ,3 ]
Getmantsev, Evgeny [1 ]
Menshikov, L., I [1 ,4 ]
Fedichev, Peter O. [1 ,5 ]
Aulchenko, Yurii [2 ,3 ,6 ,7 ]
机构
[1] Gero LLC, Novokuznetskaya St 24-2, Moscow 119017, Russia
[2] Novosibirsk State Univ, Pirogova 2, Novosibirsk 630090, Russia
[3] Inst Cytol & Genet SB RAS, Lavrentyeva Ave 10, Novosibirsk 630090, Russia
[4] Natl Res Ctr, Kurchatov Inst, 1 Akad Kurchatova Pl, Moscow 123182, Russia
[5] Moscow Inst Phys & Technol, Inst Skii Per 9, Moscow 141700, Russia
[6] PolyOmica, Het Vlaggeschip 61, NL-5237 PA Shertogenbosch, Netherlands
[7] Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland
关键词
GENOME-WIDE ASSOCIATION; LD SCORE REGRESSION; LIFE-SPAN; HUMAN LONGEVITY; VARIANTS; RISK; SUSCEPTIBILITY; METAANALYSIS; GWAS; LIMITATIONS;
D O I
10.1038/s42003-019-0290-0
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Aging populations face diminishing quality of life due to increased disease and morbidity. These challenges call for longevity research to focus on understanding the pathways controlling healthspan. We use the data from the UK Biobank (UKB) cohort and observe that the risks of major chronic diseases increased exponentially and double every eight years, i.e., at a rate compatible with the Gompertz mortality law. Assuming that aging drives the acceleration in morbidity rates, we build a risk model to predict the age at the end of healthspan depending on age, gender, and genetic background. Using the sub-population of 300,447 British individuals as a discovery cohort, we identify 12 loci associated with healthspan at the whole-genome significance level. We find strong genetic correlations between healthspan and all-cause mortality, life-history, and lifestyle traits. We thereby conclude that the healthspan offers a promising new way to interrogate the genetics of human longevity.
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页数:11
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