Longevity defined as top 10% survivors and beyond is transmitted as a quantitative genetic trait.
Niels van den BergMar Rodríguez-GirondoIngrid K van DijkRick J MouritsKees MandemakersAngelique A P O JanssensMarian BeekmanKen R SmithP Eline SlagboomPublished in: Nature communications (2019)
Survival to extreme ages clusters within families. However, identifying genetic loci conferring longevity and low morbidity in such longevous families is challenging. There is debate concerning the survival percentile that best isolates the genetic component in longevity. Here, we use three-generational mortality data from two large datasets, UPDB (US) and LINKS (Netherlands). We study 20,360 unselected families containing index persons, their parents, siblings, spouses, and children, comprising 314,819 individuals. Our analyses provide strong evidence that longevity is transmitted as a quantitative genetic trait among survivors up to the top 10% of their birth cohort. We subsequently show a survival advantage, mounting to 31%, for individuals with top 10% surviving first and second-degree relatives in both databases and across generations, even in the presence of non-longevous parents. To guide future genetic studies, we suggest to base case selection on top 10% survivors of their birth cohort with equally long-lived family members.
Keyphrases
- genome wide
- young adults
- copy number
- dna methylation
- high resolution
- drosophila melanogaster
- type diabetes
- gene expression
- free survival
- big data
- machine learning
- electronic health record
- coronary artery disease
- risk factors
- cardiovascular events
- artificial intelligence
- intellectual disability
- mass spectrometry
- rna seq
- data analysis