Is Extreme Longevity Genetic? Scientists Find Centenarians Lack Genes Underlying Certain Chronic Diseases

New research finds centenarians lack some genetic variants that predispose others to chronic disease. Jean Bajean, CC BY-SA 2.0

Age is the largest risk factor for multiple chronic diseases — yet, we know so little about the specific genetic differences that contribute to varying life expectancies (no matter how much this woman tells us it's to drink Miller High Life). Or at least we did prior to a recent study published in the journal PLoS Genetics.

A group of U.S. and international researchers cited genetic studies have thus far identified a single gene, APOE, absent in centenarians, or the people who are one hundred or more years old. APOE is a genetic variant believed to increase an individual's risk for developing Alzheimer's disease, which suggests centenarians may lack other disease variants. To find out, researchers designed a statistical model to apply to "genome-wide summary data" from 24 disease-related case and control studies, as well as quantitative traits like cholesterol levels from online web resources to pinpoint genes associated with longevity.

The model is called informed GWAS (iGWAS), and it works to better "derive a vector of weights for longevity GWAS." Researchers could gather information for different disease and traits that may be strongly implicated in one or more chronic diseases. And the results showed nine of 21 disease-related GWAS had significant genetic overlap with longevity.

For instance, at one point, researchers made a list of the top ranking single nucleotide polymorphisms (SNPs) — a variation in a single base pair in a DNA sequence — from a certain disease study. They applied values for the longevity data in order to directly test whether "the allele [genetic variant] enriched in disease is depleted in longevity." So in the plots for coronary artery disease and Alzheimer’s disease, researchers found "the curves formed by the top disease SNPs are shifted left from the lines expected by a random distribution, indicating that some of the SNPs in the list are associated with longevity."

Researchers ultimately identified five longevity loci (the specific location of a gene) that provide clues about physiological mechanisms for successful aging, including APOE, ABO, and SH2BH3. 

"We have shown that one of the genetic mechanisms for extreme longevity involves the avoidance of certain risk alleles that predispose to common diseases, including coronary artery disease, Alzheimer’s disease, high cholesterol and chronic kidney disease," researchers wrote. "For these diseases, QQ plots show that some of the top disease SNPs have increased likelihood of having low P values for longevity, with the risk allele for disease showing depletion in centenarians."

That said, researchers added "it is also plausible that centenarians carry a different genetic background than the normal population consisting of protective SNPs that predispose for extreme longevity." Future research is needed before researchers can say for sure.

Source: Fortney K, Dobriban E, Garagnani P, Pirazzini C, Monti D, Mari D, et al. Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity. PLoS Genetics. 2015.

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