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 aging 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.
We aim to identify factors associated with being free of major age related diseases and being at the healthier end of measures related to functioning and disease processes in ageing.
Luke C. Pilling, et al. Red Blood Cell Distribution Width: genetic evidence for aging pathways in 116,666 volunteers.
|Lead investigator:||David Melzer|
|Lead institution:||University of Exeter|