期刊
PLOS ONE
卷 12, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0185083
关键词
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资金
- UK Medical Research Council [MR/M023095/1]
- Medical Research Council [MR/M005070/1]
- Diabetes Research and Wellness Foundation Fellowship
- Wellcome Trust
- Royal Society [104150/Z/14/Z]
- Wellcome Trust Institutional Strategic Support Award [WT097835MF]
- European Research Council [323195:GLUCOSEGENES-FP7-IDEAS-ERC]
- Intramural Research Program of the National Institute on Aging
- U.S. National Institutes of Health
- University of Connecticut Health Center
- Medical Research Council [MR/M023095/1, MC_qA137853] Funding Source: researchfish
- MRC [MR/M023095/1] Funding Source: UKRI
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 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.
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