ageing, healthy ageing, biomarkers, gene discovery
Conditions
Interventions
 
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
65 Years to 99 Years
Inclusion criteria
Inclusion criteria: Longevity Relatives Count (LRC) expresses a score indicating the percentage of ancestors surviving into a specific top percentile of their birth cohort. We focus on LRC 30%. Cases LRC>=30%: - Able to give written consent - Willing and able to follow the study protocol - LRC-score 30% and up in - Age >= 75 years - At least one sibling or first cousin with age >= 75 years who has given written consent Controls LRC=0%: - Able to give written consent - Willing and able to follow the study protocol - LRC-score 0% in our - Age >= 75 years
Exclusion criteria
Exclusion criteria: - Not be able to give (written) informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Our primary analyses are A) within cases: a non-parametric linkage analysis to establish likely genomic regions of longevity genes in researched families, to this end we will solely use the families defined as cases (LRC>=30%). B) between cases and control: we compare social and behavioural factor that associate with familial longevity in the cases and controles. A Genetic analysis. Primary analysis. In the linkage analysis you compare familymember on marker positions , bases on single-nucleotide polymorphism (SNP) -arrya genotyping data, and you test whether the 'longevity-affected- familymember share more alleles than chance (allele frequentie in the population) then expected on these marker positions. The more member from one family you can include the more power you will have in you analysis. From this comes a logarithm-of-the-odds (LOD)-score. We shall focus on regions with a peak LOD-score of 3 or higher (this indicates that it is at least 1000x likely that the longevity gene lies on that position and not somewhere else on the genome) and encompasses a region between the peak and 1-LOD-drop. In the DNA of member of these families contributing to these linkage signals we shall perform whole-genome-sequencing (WGS). From this sequencing data we shall select genetic variant that are shared between all familymember that positively contribute to the linkage signals. Relevant genevariants shall be selected within the linkage-regions in one of two ways. Firstly, we shall select very rare genvariant that have a predicted functional through an in sillico procedure, based on predicted rare protein altering gene variants (minor allele frequency (MAF) < 0,2%)> Secondly we select on more common variants (common SNPs) in chromosome regions under the linkage signals. Secundaire analyses: Variants in the same gene in multiple families contributing to the linkage signals shall be candidates for further studies into the function of how these genes contribute to healthy | — |
Secondary
| Measure | Time frame |
|---|---|
| - | — |
Countries
Netherlands
Contacts
Public ContactPC Putter
Leids Universitair Medisch Centrum
Outcome results
None listed