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August 03, 2010

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Group of genes may predict longevity with 77% accuracy

July 2, 2010
Courtesy of Boston University Medical Center
and World Science staff

Re­search­ers have iden­ti­fied a group of genes that they say can be used to pre­dict with 77 per­cent ac­cu­ra­cy whe­ther people will live ex­cep­tion­ally long.

The find­ing is a break­through in un­der­stand­ing the role of genes in de­ter­min­ing hu­man life­span, ac­cord­ing to the sci­en­tists.

They stressed that en­vi­ron­ment and family his­to­ry are al­so fac­tors in healthy ag­ing. Yet the study “shows that ge­net­ic da­ta can in­deed pre­dict ex­cep­tion­al longe­vity with­out knowl­edge of any oth­er risk fac­tor,” wrote the researchers in their re­port, pub­lished July 1 on­line by the re­search jour­nal Sci­ence.

“Fur­ther in­ves­ti­ga­t­ion is needed to un­der­stand how and why these vari­ants col­lec­tively pre­dis­pose for ex­cep­tion­al longe­vity,” added the in­ves­ti­gators, from Bos­ton Uni­vers­ity Schools of Pub­lic Health and Med­i­cine and Bos­ton Med­i­cal Cen­ter.

The team con­ducted a genome-wide gene as­socia­t­ion study in cen­te­nar­ians, who of­ten don’t suf­fer age-related dis­abil­i­ties un­til well in­to their mid-nineties. Re­search­ers led by Bos­ton Uni­vers­ity’s Paola Se­bas­tiani and Thom­as Perls built a ge­net­ic mod­el that in­cludes 150 ge­net­ic vari­ants, and which they said could be used to pre­dict wheth­er a per­son lived to the late 90s or old­er.

The anal­y­sis al­so iden­ti­fied 19 ge­net­ic clus­ters or “ge­net­ic sig­na­tures” of ex­cep­tion­al longe­vity that they said char­ac­ter­ized nine in ten cen­te­nar­ians stud­ied. The sig­na­tures cor­re­lat­ed with dif­fer­ences in the prev­a­lence and age-of-onset of dis­eases such as de­men­tia and hy­per­ten­sion, and may help iden­ti­fy key sub­groups show­ing healthy ag­ing, the au­thors said.

The team found that 45 per­cent of the old­est cen­te­nar­ians – those 110 years and old­er – had a ge­net­ic sig­na­ture with the high­est pro­por­tion of longe­vity-as­sociated ge­net­ic vari­ants. “These ge­net­ic sig­na­tures are a new ad­vance to­wards per­sonalized ge­nomics and pre­dictive med­i­cine, where this an­a­lyt­ic meth­od may prove to be gen­er­ally use­ful in pre­ven­tion and screen­ing of nu­mer­ous dis­eases, as well as the tai­lored uses of med­ica­t­ions,” said Perls.

The re­search­ers de­vel­oped a new sta­tis­ti­cal ap­proach to an­a­lyze ge­net­ic da­ta from more than 1,000 cen­te­nar­ians and sev­er­al con­trol groups, and to iden­ti­fy vari­ants most pre­dictive of be­ing cen­te­nar­ians or not. “The meth­odology that we de­vel­oped can be ap­plied to oth­er com­plex ge­net­ic traits, in­clud­ing Alzheimer’s dis­ease, Parkin­son’s, car­di­o­vas­cu­lar dis­ease and di­a­be­tes,” Se­bas­tiani said.

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Researchers have identified a group of genes that they say can predict exceptional longevity in humans with 77 percent accuracy. The finding is a breakthrough in understanding the role of genes in determining human lifespan, according to the scientists, who stressed that environment and family history are also factors in healthy aging. The study, from researchers at the Boston University Schools of Public Health and Medicine and Boston Medical Center, was released July 1 online by the journal Science. The team conducted a genome-wide gene association study in centenarians, who often don’t display age-related disabilities until well into their mid-nineties. Researchers led by Boston University’s Paola Sebastiani and Thomas Perls built a genetic model that includes 150 genetic variants, and which they said could be used to predict whether a person lived to the late 90s or older. The analysis also identified 19 genetic clusters or “genetic signatures” of exceptional longevity that characterized nine in ten of the centenarians studied. The signatures correlated with differences in the prevalence and age-of-onset of diseases such as dementia and hypertension, and may help identify key subgroups of healthy aging, the authors said. The team found that 45 percent of the oldest centenarians – those 110 years and older – had a genetic signature with the highest proportion of longevity-associated genetic variants. “These genetic signatures are a new advance towards personalized genomics and predictive medicine, where this analytic method may prove to be generally useful in prevention and screening of numerous diseases, as well as the tailored uses of medications,” said Perls. The researchers developed a new statistical approach to analyze genetic data from more than 1,000 centenarians and several control groups, and to identify variants most predictive of being centenarians or controls. “The methodology that we developed can be applied to other complex genetic traits, including Alzheimer’s disease, Parkinson’s, cardiovascular disease and diabetes. It reinvigorates the potential high utility of collecting and analyzing such data,” Sebastiani said. The authors wrote that their preliminary data “suggest that exceptional longevity may be the result of an enrichment of longevity-associated variants that counter the effect of disease-associated variants.” They added that “further investigation is needed to understand how and why these variants collectively predispose for exceptional longevity.” The researchers noted that the 77-percent accuracy rate of predictions “shows that genetic data can indeed predict exceptional longevity without knowledge of any other risk factor.”