Whole-Genome Sequencing of the World’s Oldest People
Level 4 - case-series / case-control
Case-control genomic sequencing study with a small sample series
OpenAlex W2009026465 · doi:10.1371/journal.pone.0112430
What was done
Whole-genome sequencing was performed on 17 supercentenarians (aged 110 years or older) and compared to control genomes to search for enrichment of rare protein-altering variants. The candidate gene with the highest enrichment, TSHZ3, was subsequently sequenced in a secondary follow-up cohort of 99 long-lived individuals.
What was found
No significant enrichment was detected for any single rare protein-altering variant or for any gene harboring different rare protein-altering variants in supercentenarians relative to controls. Follow-up sequencing of TSHZ3 in 99 long-lived individuals also failed to find significant enrichment. One supercentenarian carried an incidental pathogenic mutation in DSC2 (associated with arrhythmogenic right ventricular cardiomyopathy) despite surviving past 110 years.
Why it matters
This study indicates that extreme longevity is not readily explained by common single rare protein-altering variants with large effects across supercentenarians.
Limits
The primary sample size is extremely small (n = 17), providing very low statistical power to detect rare genetic associations. The abstract does not detail the nature or ancestry of the control cohort, nor does it quantify effect sizes or non-coding regulatory variation.
Cited by
- supports Only about 300 living people worldwide are supercentenarians aged 110 and older.