Lack of replication of genetic associations with human longevity

Valeria Novelli, Chiara Viviani Anselmi, Roberta Roncarati, Guia Guffanti, Alberto Malovini, Giulio Piluso, Annibale Alessandro Puca

Research output: Contribution to journalArticle

Abstract

The exceptional longevity of centenarians is due in part to inherited genetic factors, as deduced from data that show that first degree relatives of centenarians live longer and have reduced overall mortality. In recent years, a number of groups have performed genetic association studies on long-living individuals (LLI) and young controls to identify alleles that are either positively or negatively selected in the centenarian population as consequence of a demographic pressure. Many of the reported studies have shown genetic loci associated with longevity. Of these, with the exception of APOE, none have been convincingly reproduced. We validated our populations by typing the APOE locus. In addition, we used 749 American Caucasian LLI, organized in two independent tiers and 355 American Caucasian controls in the attempt to replicate previously published findings. We tested Klotho (KL)-VS variant (rs952706), Cholesteryl Ester Transfer Protein (CETP) I405V (rs5882), Paraoxonase 1 (PON1) Q192R (rs662), Apolipoprotein C-III (APOC3) -641C/A (rs2542052), Microsomal Transfer Protein (MTP) -493G/T (rs2866164) and apolipoprotein E (APOE) ε2 and ε4 isoforms, (rs7412 and rs429358) haplotypes respectively. Our results show that, at present, except for APOE, none of the selected genes show association with longevity if carefully tested in a large cohort of LLI and their controls, pointing to the need of larger populations for case-control studies in extreme longevity.

Original languageEnglish
Pages (from-to)85-92
Number of pages8
JournalBiogerontology
Volume9
Issue number2
DOIs
Publication statusPublished - Apr 2008

Keywords

  • Association studies
  • Long living individuals
  • Longevity

ASJC Scopus subject areas

  • Geriatrics and Gerontology

Fingerprint Dive into the research topics of 'Lack of replication of genetic associations with human longevity'. Together they form a unique fingerprint.

  • Cite this