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Largest study - to date - of genes linked to lifespan biomarkers

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Bayesian association scan reveals loci associated with human lifespan and linked biomarkers

 

Abstract

 

The enormous variation in human lifespan is in part due to a myriad of sequence variants, only a few of which have been revealed to date. Since many life-shortening events are related to diseases, we developed a Mendelian randomization-based method combining 58 disease-related GWA studies to derive longevity priors for all HapMap SNPs. A Bayesian association scan, informed by these priors, for parental age of death in the UK Biobank study (n=116,279) revealed 16 independent SNPs with significant Bayes factor at a 5% false discovery rate (FDR). Eleven of them replicate (5% FDR) in five independent longevity studies combined; all but three are depleted of the life-shortening alleles in older Biobank participants. Further analysis revealed that brain expression levels of nearby genes (RBM6, SULT1A1 and CHRNA5) might be causally implicated in longevity. Gene expression and caloric restriction experiments in model organisms confirm the conserved role for RBM6 and SULT1A1 in modulating lifespan.

 

A pop writeup:
 

https://www.sciencedaily.com/releases/2017/07/170727105146.htm

 

 

"The answer to how long each of us will live is partly encoded in our genome. Researchers have identified 16 genetic markers associated with a decreased lifespan, including 14 new to science. This is the largest set of markers of lifespan uncovered to date."

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When you dig into it, this is a misleadingly-headlined story: this was not a study of gene variants' relationship with lifespan in the way that the term is used by biogerontologists (ie, maximum lifespan (rodents) or "extreme longevity" or centenarianism in humans — the limits of life, where survival is dominated by aging rather than premature mortality due to lifestyle factors): they call this "longevity." They are instead focused on genes' effects on "lifespan [sic] in a general population cohort of the UK Biobank study14rather than extreme longevity":

 

 

While most determinants of life expectancy are still environmental (for example, socio-economic status, smoking and other lifestyle factors and gender1), numerous twin studies5 suggest that in modern societies 20–30% of human lifespan variation is due to genetic factors, perhaps up to 40% when looking at survival beyond 85–100 years, often termed longevity1,6,7. Longer lifespan is strongly associated with later disease onset and as such is likely influenced by many genetic variants via predisposition to, or protection from certain diseases5, or their risk factors. ...

 

[They operationalize "lifespan" as] the hazard ratio (HR) for survival beyond age 40 ...

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