Introduction: Variability in red blood cell volumes (distribution width, RDW) increases with age and is strongly predictive of mortality, incident coronary heart disease and cancer. We investigated inherited genetic variation associated with RDW in 116,666 UK Biobank human volunteers.
Results: A large proportion RDW is explained by genetic variants (29%), especially in the older group (60+ year olds, 33.8%, <50 year olds, 28.4%). RDW was associated with 194 independent genetic signals; 71 are known for conditions including autoimmune disease, certain cancers, BMI, Alzheimer's disease, longevity, age at menopause, bone density, myositis, Parkinson's disease, and age-related macular degeneration. Exclusion of anemic participants did not affect the overall findings. Pathways analysis showed enrichment for telomere maintenance, ribosomal RNA, and apoptosis. The majority of RDW-associated signals were intronic (119 of 194), including SNP rs6602909 located in an intron of oncogene GAS6, an eQTL in whole blood.
Conclusions: Although increased RDW is predictive of cardiovascular outcomes, this was not explained by known CVD or related lipid genetic risks, and a RDW genetic score was not predictive ofincident disease. The predictive value of RDW for a range of negative health outcomes may in part be due to variants influencing fundamental pathways of aging.
Pilling LC, Atkins JL, Duff MO, Beaumont RN, Jones SE, Tyrrell J, et al. (2017) Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers. PLoS ONE 12(9): e0185083.
Genetic and environmental influences on ageing well
We aim to identify risk factors and genetic variants associated with ageing well - i.e. having the best health status in the seventh decade of life
We aim to identify factors associated with being free of major ageing diseases (cardiovascular disease, stroke, diabetes, depression or cancer) and consistently in the healthiest range of measures such as muscle strength, cognition, lung function, bone mineral density and blood pressure and key blood tests.
Genome wide association studies (GWAS) will identify associated variants for the summary phenotype and for the main components included.
This project has been funded by the Medical Research Council. Our underlying aim is to find new ways of helping those who develop earlier onset age-related disease and loss of function, by applying insights gained from those who age well. The conventional and genetic factors associated with ageing well should help reveal the underlying mechanisms and perhaps provide markers for identifying early problems or monitoring progression in each of the components of ageing well. This project involves analysis of the existing data, with collaborations to allow independent replication of findings.
We will use statistical methods to optimize the classification of ageing well and its component traits. We will pay particular attention to those in the seventh decade of life, but also examine associations in younger groups and test for interactions with advancing age. We will use standard statistical modelling approaches to identify and characterise conventional measures associated with ageing well. We will also use genome wide association study approaches to identify genetic variants statistically associated with ageing well and its components. The full cohort, with special focus on the 217000 respondents aged 60 to 69 at baseline
|Lead investigator:||Professor David Melzer|
|Lead institution:||University of Exeter|
1 related Return
|Return ID||App ID||Description||Archive Date|
|1623||14631||Impact of Low Cardiovascular Risk Profiles on Geriatric Outcomes: Evidence From 421,000 Participants in Two Cohorts||21 May 2019|
|736||Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers||Pilling et al||2017||PLos One 2017|