Acknowledgements: We thank the GEHA Genetics of Healthy Ageing Consortium under the Sixth Framework Programme for RTD of the European Commission Priority 1: Life sciences, Genomics and Biotechnology for health (contract no. LSHM-CT-2004-503270). For excellent technical assistance, we acknowledge the laboratory personnel of the Institute of Clinical Molecular Biology at the Christian-Albrechts-University Kiel. We thank the Biological Resource Center at the Fondation Jean Dausset-CEPH for preparing and genotyping DNA samples of the French Population. Moreover, as the results of association studies in German, Central Italian and Southern Italian populations were different, we thought it worthwhile to carry out additional genotyping in the French cohort to reach more clear-cut results. However, the results deflate significance, reinforcing the interpretation that we are likely dealing with population specificity.

References: The case-control study design has limitations in highlighting polymorphisms displaying U-shape patterns of genotype frequencies. The groups of Franceschi and De Benedictis earlier stressed the likelihood of a genetic variant to exert different effects at different ages, and a cross-sectional study design in which two age groups are compared may not be able to identify all variants potentially associated with such a complex phenotype.

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