Journal Article

Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers

Wood, Andrew R., Weedon, Michael N., Jones, Samuel E., Murray, Anna, Tyrrell, Jessica, Tuke, Marcus A., Kuchel, George A., Beaumont, Robin N., Melzer, David, Harries, Lorna W., Atkins, Janice L., Kuo, Chia-Ling, Duff, Michael O., Ruth, Katherine S., Yaghootkar, Hanieh, Frayling, Timothy M., Pilling, Luke C., Ferrucci, Luigi

2017

Overview

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. 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. 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 of incident 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Age related diseases / Aged / Aging / Aging (Biology) / Aging - blood / Aging - genetics / Anemia / Apoptosis / Biological Specimen Banks / Biology and Life Sciences / Blood / Blood cells / Body mass / Bone density / Cancer / Cardiovascular diseases / Coronary artery disease / Coronary heart disease / Disease / DNA methylation / Epidemiology / Erythrocyte Indices - genetics / Erythrocytes / Female / Gene expression / Gene Ontology / Genetic aspects / Genetic diversity / Genetic Predisposition to Disease / Genetic variance / Genetic Variation / Genetics / Genome-Wide Association Study / Genomes / Genomics / Genotype / Healthy Volunteers / Heart / Heart diseases / Hematology / Hospitals / Humans / Internet / Longevity / Macular degeneration / Male / Medical prognosis / Medical schools / Medicine and Health Sciences / Menopause / Middle Aged / Myositis / Parkinson's disease / Physiological aspects / Principal components analysis / Prognosis / Public health / Red blood cells / Ribonucleic acid / RNA / rRNA / Signal Transduction - genetics / Single-nucleotide polymorphism / Studies / United Kingdom