A novel sampling design to explore gene-longevity associations: The ECHA study

Francesco De Rango, Serena Dato, Dina Bellizzi, Giuseppina Rose, Erika Marzi, Luca Cavallone, Claudio Franceschi, Axel Skytthe, Bernard Jeune, Amandine Cournil, Jean Marie Robine, Jutta Gampe, James W. Vaupel, Vincenzo Mari, Emidio Feraco, Giuseppe Passarino, Andrea Novelletto, Giovanna De Benedictis

Research output: Contribution to journalArticlepeer-review


To investigate the genetic contribution to familial similarity in longevity, we set up a novel experimental design where cousin-pairs born from siblings who were concordant or discordant for the longevity trait were analyzed. To check this design, two chromosomal regions already known to encompass longevity-related genes were examined: 6p21.3 (genes TNFα, TNFβ, HSP70.1) and 11p15.5 (genes SIRT3, HRAS1, IGF2, INS, TH). Population pools of 1.6, 2.3 and 2.0 million inhabitants were screened, respectively, in Denmark, France and Italy to identify families matching the design requirements. A total of 234 trios composed by one centenarian, his/her child and a child of his/her concordant or discordant sib were collected. By using population-specific allele frequencies, we reconstructed haplotype phase and estimated the likelihood of Identical By Descent (IBD) haplotype sharing in cousin-pairs born from concordant and discordant siblings. In addition, we analyzed haplotype transmission from centenarians to offspring, and a statistically significant Transmission Ratio Distortion (TRD) was observed for both chromosomal regions in the discordant families (P=0.007 for 6p21.3 and P=0.015 for 11p15.5). In concordant families, a marginally significant TRD was observed at 6p21.3 only (P=0.06). Although no significant difference emerged between the two groups of cousin-pairs, our study gave new insights on the hindrances to recruiting a suitable sample to obtain significant IBD data on longevity-related chromosomal regions. This will allow to dimension future sampling campaigns to study-genetic basis of human longevity.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalEuropean Journal of Human Genetics
Issue number2
Publication statusPublished - Feb 2008

ASJC Scopus subject areas

  • Genetics(clinical)


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