GWAS and Meta-Analysis in Aging/Longevity.
Longevity is an extremely complex phenotype that is determined by environment, life style and genetics. Genome wide association studies (GWAS) have been a powerful tool to identify the genetic origin of other complex outcome with a similar heritability. In this chapter we discuss the findings all GWAS of longevity conducted to date. Various cut-off to define longevity have been used varying from 85+, 90+ and 100+ years and the impact of these difference are addressed in this chapter. The only consistent association emerging from GWAS to data is the APOE gene that has been already identified as a candidate gene. Although (GWAS) have identified biologically plausible genes and pathways, no new loci for longevity have been conclusively proven. A reason for not finding any replicated associations for longevity could be the complexity of the phenotype, although heterogeneity also underlies many other traits for which GWAS has been successful. One may argue that rare variants explain the high heritability of longevity and the segregation of the trait in families. Yet, whole genome analyses of GWAS data still suggest that over 80 % of the heritability is explained by common variants. Although findings of GWAS to date have been disappointing, there is ample opportunity to improve the statistical power of studies to find common variants with small effects. In the near future, joining of the published studies and new ones emerging may bring to surface new loci.
Department of Epidemiology, Erasmus University Medical Center, Dr. Molewaterplein 50, PO-Box 2040, 3000 CA, Rotterdam, Netherlands, l.broer@erasmusmc.nl.
Linda
L
Broer
Cornelia M
CM
van Duijn
D000375:Aging / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008136:Longevity / Q000235:genetics*