Sci. Aging Knowl. Environ., 26 May 2004
Vol. 2004, Issue 21, p. pe23
[DOI: 10.1126/sageke.2004.21.pe23]

PERSPECTIVES

GEHA--The Pan-European "Genetics of Healthy Aging" Project

Almut Nebel, and Stefan Schreiber

The authors are at the Institute for Clinical Molecular Biology at the University Hospital of the Christian Albrechts-University, 24105 Kiel, Germany. E-mail: s.schreiber{at}mucosa.de (S.S.)

http://sageke.sciencemag.org/cgi/content/full/2004/21/pe23

Key Words: genetic predisposition • healthy aging • microsatellite • single nucleotide polymorphism (SNP) • ApoE

Introduction

With people living longer lives throughout the industrialized world, there is a need for research that focuses on how we can promote good health during the process of aging in addition to research on treating age-related diseases. The process of aging in humans is complex and involves both genetic and environmental factors (see "Aging Research Grows Up"). The genes that predispose some people to remain healthy and active well into their nineties and beyond will be investigated by the pan-European "GEnetics of Healthy Aging" (GEHA) consortium, which officially started in a festive opening ceremony in Bologna, Italy, on 22 May 2004. This largest-ever study of long-lived individuals is headed by Professor Claudio Franceschi of the University of Bologna and is funded with {euro}7.2 million by the Sixth Framework Programme of the European Union. Twenty-two research institutions from 10 European countries (Italy, Germany, France, the United Kingdom, Belgium, Denmark, Finland, the Netherlands, Greece, and Poland) are participating, as well as institutes from Israel and the People's Republic of China. The GEHA group unites demographers, geriatricians, geneticists, genetic epidemiologists, molecular biologists, bioinformaticians, and statisticians. This interdisciplinary critical mass would be impossible to attain by any of the countries alone; the GEHA consortium is expected to achieve scientific (European) collaboration and integration at a hitherto unprecedented level.

Aims of Project

The aim of GEHA is to identify genes involved in healthy aging and longevity in a systematic manner. The idea is that certain variants of these genes would allow individuals to survive to advanced old age with good cognitive and physical function.

More specifically, the working plan of this project is to (i) collect a very large number (2800) of long-lived pairs of siblings (sibpairs) (both aged 90+ years) from the 10 European countries and Israel; (ii) perform a genome-wide microsatellite linkage scan in all the sibpairs (a total of 5600 individuals) to identify genetic markers that are associated with longevity; (iii) investigate the following three genomic regions previously identified as being relevant to aging and longevity: chromosome 4 (region D4S1564), chromosome 11 (11p15.5), and chromosome 19 [around the ApoE gene (see Raber Review)] by genotyping of single nucleotide polymorphisms (SNPs) in both cases (that is, representatives from each of the 2800 sibpairs) and controls (2800 young individuals); (iv) determine whether mitochondrial DNA haplogroups and mutations previously associated with longevity are present in the long-lived individuals; (v) compare the findings from the European populations with those from the ethnically different Han Chinese (contributed by the Beijing Genomics Institute); and (vi) identify genes involved in healthy aging and longevity in a gender-specific manner in different ethnic and geographic groups.

Additional advanced approaches (bioinformatics, advanced statistics, mathematical modeling, molecular genetics, functional genomics, and proteomics) are envisaged to identify and map the gene variant(s) of interest. Mathematical and statistical models will be developed that are capable of combining genetic data with information about demographic characteristics, health status, socioeconomic factors, and life-style habits. All of the information will be stored in a centralized database.

German Contributions

The genetic analysis will be performed on eight high-throughput technology platforms in Germany, Italy, France, the Netherlands, the United Kingdom, and Finland. The German national genotyping center in Kiel is one of the major platforms in the GEHA project and will be particularly involved in the exploration of the three candidate regions on chromosomes 4, 11, and 19 and of other chromosomal regions detected by linkage analysis.

The German contribution to the GEHA project is represented by the Institute for Clinical Molecular Biology at the Christian Albrechts-University in Kiel and the Max Planck Institute for Demographic Research in Rostock. The Institute for Clinical Molecular Biology (Director: Stefan Schreiber) has previously explored the genetic basis of polygenic conditions (for example, inflammatory bowel disease) by positional cloning and linkage disequilibrium mapping. The research group has experience in generating, storing, and analyzing large data sets. Funded by the German National Genome Research Network (NGFN), the Kiel center established a high-throughput SNP genotyping platform 3 years ago. The Institute for Clinical Molecular Biology will contribute to the sample collection and will provide systematic association mapping to the consortium.

The Max Planck Institute for Demographic Research (Directors: James Vaupel and Jan Hoem) is the second largest demographic research institute in Europe. It has provided expertise and infrastructure in the fields of biodemography of aging, advanced demographic and statistical analysis, and methods for analyzing data on genes and longevity. The infrastructure also includes large data collections related to mortality and longevity.


May 26, 2004 Citation: A. Nebel, S. Schreiber, GEHA--The Pan-European "Genetics of Healthy Aging" Project. Sci. Aging Knowl. Environ. 2004 (21), pe23 (2004).








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