Aimed to define how genetic variations relate to differences in capability and wellbeing and to modifiable risk factors.
Prof Ian Day introduces Genetics
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What does genetics have to do with population studies?
The application of genetics to studying large groups of people is relatively new. Previously expensive genetic tests for research studies are falling in price and simultaneously becoming more sophisticated, allowing us to gather large amounts of genetic information in large population studies.
Seeing the interplay between genetics and environment on such a large scale should allow us to see relationships that have remained elusive.
How was the research undertaken?
We took genetic markers that we knew about already (such as those for specific common diseases) and tested whether they were associated with markers of ageing including measures of physical and cognitive capability.
Drawing on published and unpublished findings from other genome studies we selected specific genetic markers to measure in all the cohorts. As prices have fallen enough we were able to study large batches of markers. Such markers were drawn from research on diseases such as breast, prostate and colon cancers, heart disease and risks for heart disease, and depression, arthritis, Parkinson’s and Alzheimer’s disease.
What we are researching
We looked to find out two things:
- If there were further undiscovered relationships between important common genetic variations and capability, and other age-related phenotypes.
- If any of these important genetic variations would lead us to identify factors (anything from any specific nutritional, environmental, or behavioural factors or even some known medicine) which might beneficially be modified to improve capability and wellbeing.
We have been involved in ongoing training for these new methods as we were confident that these systematic approaches would become increasingly important and would need skilled young workers. We have also contributed to public understanding of this type of research and the issues involved through radio interviews.
What have we found so far?
- We found no consistent evidence, across the HALCyon cohorts, of associations between common polymorphisms of TERT, a telomere maintenance gene, and a range of ageing related phenotypes including markers of cognitive and physical capability, blood pressure, blood lipid levels, lung function, and others. This suggests that despite previously having been shown to be associated with several cancers this genotype was not an important influence on other markers of ageing (Alfred et al., Aging Cell 2011).
- We combined results from a systematic review and meta-analysis of published data with new analyses undertaken across the HALCyon cohorts to formally re-evaluate the claims that the ACTN3 genotype influences sporting performance. Our systematic review found evidence of an effect of this genotype on power/sprint athletic status in Europeans but that there was no evidence of an effect of this genotype on physical capability in the general population (Alfred et al., Human Mutation 2011).
- In a large, multi-cohort investigation we reported that there was no association between polymorphisms in the growth hormone/insulin-like growth factor (GH/IGF) axis and physical capability (Alfred et al., PLoS One 2012).
- In meta-analyses including data from five HALCyon cohorts, associations between a polymorphism in the pleiotropic GCKR and higher triglycerides and lower glucose levels were confirmed. However, no associations were found between this SNP and physical or cognitive capability (Alfred et al., PLoS One 2013).
- Across 6 UK cohorts we found little evidence of association between polymorphisms that influence biomarkers of nutrition and cognitive capability (Alfred et al., Journal of Nutrition 2013)
- In a study of the associations of genetic markers of joint and bone health with physical capability in 6 UK cohorts, there was limited evidence of association. However, carriers of the serum calcium-raising allele were found to have weaker grip strength than non-carriers (Alfred et al., Bone 2013).
Please see the Case for Support for a detailed, more technical overview of the work packages.
Kuh D, Cooper R, Hardy R, Richards M, Ben-Shlomo Y (Eds). A life course approach to healthy ageing. Oxford University Press to be published January 9th 2014.
- Chapter 14: Genetic aspects of ageing
Ms Teri-Louise Davies, Dr Tamuno Alfred and Professor Ian Day