title: Limitations and risks of meta-analyses of longevity studies.
abstract: Searching for genetic determinants of human longevity has been challenged by the rarity of data sets with large numbers of individuals who have reached extreme old age, inconsistent definitions of the phenotype, and the difficulty of defining appropriate controls. Meta-analysis - a statistical method to summarize results from different studies - has become a common tool in genetic epidemiology to accrue large sample sizes for powerful genetic association studies. In conducting a meta-analysis of studies of human longevity however, particular attention must be made to the definition of cases and controls (including their health status) and on the effect of possible confounders such as sex and ethnicity upon the genetic effect to be estimated. We will show examples of how a meta-analysis can inflate the false negative rates of genetic association studies or it can bias estimates of the association between a genetic variant and extreme longevity.
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA 02118, United States. Electronic address: sebas@bu.edu.
authors.forename: Paola
authors.initials: P
authors.lastname: Sebastiani
authors.affiliation: College of Public Health and Human Sciences, Oregon State University, 151 Milam Hall, Corvallis, OR, United States. Electronic address: Harold.Bae@oregonstate.edu.
authors.forename: Harold
authors.initials: H
authors.lastname: Bae
authors.affiliation: Bioinformatics Program, Boston University, 44 Cummington Mall, Boston, MA 02215, United States. Electronic address: agurinov@bu.edu.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Gurinovich
authors.affiliation: The Danish Aging Research Center, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9 B, St., 5000 Odense C, Denmark. Electronic address: msoerensen@health.sdu.dk.
authors.forename: Mette
authors.initials: M
authors.lastname: Soerensen
authors.affiliation: IRCCS MultiMedica, 20138 Milan (Mi), Italy; University of Salerno, Department of Medicine and Surgery, 84081 Baronissi, SA, Italy. Electronic address: apuca@unisa.it.
authors.forename: Annibale
authors.initials: A
authors.lastname: Puca
authors.affiliation: Geriatrics Section, Department of Medicine, Boston University School of Medicine & Boston Medical Center, 88 E Newton St., Boston, MA 02118, United States. Electronic address: thperls@bu.edu.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Perls
mesh_terms: D000369:Aged, 80 and over; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D012737:Sex Factors
keywords: Human longevity; Meta-analysis; Odds-ratios