Identifying the important SNPs in the aging pathways requires the availability of suitable phenotype measures that properly reflect the process. The traditional focus of much aging research has been on survival, and especially on extreme longevity and centenarians. However, the reported heritability of lifespan is modest - 26% for males and 23% for females. Also, it is clear that environmental factors play a strong role in survival, as genetic factors cannot explain the extraordinary rise in human longevity experienced in recent decades. In contrast to survival, certain aspects of physical functioning, notably speed of walking and standing up from the sitting position, and muscle strength in old age, appear to be highly heritable. It has reported that the heritability of performance on an 8-foot walk in the National Heart, Lung, and Blood Institute (NHLBI) Twin Study was 51%, and time to rise from a chair five times was 56%. ? Analysis of the association between each of 290 SNPs and reported limitation in walking or stair climbing has been done in 2000 Epic-Norfolk women used as controls in the EPIC-Norfolk Cancer Study done in the Norfolk region of England. These SNPs were in 100 genes that were selected as being candidates for cancers. Those studied include genes linked to oxidative damage, DNA repair, insulin like growth factors and cell cycle genes, all potentially related to aging outcomes as well as cancer. The phenotype was defined through responses of participants to the physical function domain of the Short-Form 36 questionnaire. Using samples from over 2000 additional women from the control group of that study, this work will attempt to replicate initial association findings by testing the link between 11 specific SNPs and reported mobility performance. Genotyping is now complete and the relationship to function for at least 2 of the candiadate SNP's have been replicated. A paper on this is now under review.
| Melzer, David; Murray, Anna; Hurst, Alison J et al. (2006) Effects of the diabetes linked TCF7L2 polymorphism in a representative older population. BMC Med 4:34 |
