Whole Exome Sequencing of an Exceptional Longevity Cohort

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Haakon B NygaardStephen M Strittmatter

Abstract

Centenarians represent a unique cohort to study the genetic basis for longevity and factors determining the risk of neurodegenerative disorders, including Alzheimer's disease (AD). The estimated genetic contribution to longevity is highest in centenarians and supercententenarians, but few genetic variants have been shown to clearly impact this phenotype. While the genetic risk for AD and other dementias is now well understood, the frequency of known dementia risk variants in centenarians is not fully characterized. To address these questions, we performed whole exome sequencing on 100 individuals of 98-108 years age in search of genes with large effect sizes towards the exceptional aging phenotype. Overall, we were unable to identify a rare protein-altering variant or individual genes with an increased burden of rare variants associated with exceptional longevity. Gene burden analysis revealed three genes of nominal statistical significance associated with extreme aging, including LYST, MDN1, and RBMXL1. Several genes with variants conferring an increased risk for AD and other dementias were identified, including TREM2, EPHA1, ABCA7, PLD3, MAPT, and NOTCH3. Larger centenarian studies will be required to further elucidate the ge...Continue Reading

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Citations

May 28, 2019·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Joshua M Hare, Isabel Beerman
Jul 29, 2020·Nature Metabolism·Zhengdong D ZhangJan Vijg
Jan 26, 2021·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Guillermo G TorresAlmut Nebel
Mar 11, 2021·Briefings in Functional Genomics·Maarouf BaghdadiJoris Deelen

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