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

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Aging/*blood ; Aging/*genetics ; Erythrocyte Indices/*genetics ; Signal Transduction/*genetics; Adult ; Aged ; Biological Specimen Banks ; Female ; Gene Ontology ; Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Genotype ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; United Kingdom
    • Abstract:
      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.
    • References:
      Circ J. 2015;79(5):974-5. (PMID: 25808125)
      Nat Genet. 2015 Nov;47(11):1282-1293. (PMID: 26390057)
      JAMA Oncol. 2017 May 1;3(5):636-651. (PMID: 28241208)
      Aging Cell. 2011 Oct;10(5):868-78. (PMID: 21668623)
      Int J Mol Sci. 2015 Jan 15;16(1):1873-93. (PMID: 25599528)
      Nat Genet. 2013 Oct;45(10 ):1238-1243. (PMID: 24013639)
      PLoS One. 2012;7(12):e51046. (PMID: 23226558)
      J Thorac Dis. 2015 Oct;7(10):E402-11. (PMID: 26623117)
      JAMA. 2010 Nov 24;304(20):2290-1. (PMID: 21098774)
      Nat Genet. 2015 Oct;47(10 ):1121-1130. (PMID: 26343387)
      J Gerontol A Biol Sci Med Sci. 2010 Mar;65(3):258-65. (PMID: 19880817)
      Elife. 2017 Feb 08;6:null. (PMID: 28169829)
      Cell. 2013 Jun 6;153(6):1194-217. (PMID: 23746838)
      Trends Genet. 1997 Apr;13(4):163. (PMID: 9097728)
      Cell. 2016 Nov 17;167(5):1415-1429.e19. (PMID: 27863252)
      Lab Hematol. 2004;10(1):42-53. (PMID: 15070217)
      Arch Intern Med. 2009 Mar 9;169(5):515-23. (PMID: 19273783)
      Nat Genet. 2015 Mar;47(3):284-90. (PMID: 25642633)
      Ann Transl Med. 2016 Jul;4(13):254. (PMID: 27500155)
      Aging (Albany NY). 2016 Mar;8(3):547-60. (PMID: 27015805)
      PLoS Med. 2015 Mar 31;12 (3):e1001779. (PMID: 25826379)
      Crit Rev Clin Lab Sci. 2015;52(2):86-105. (PMID: 25535770)
      Am J Hum Genet. 2007 Sep;81(3):559-75. (PMID: 17701901)
      Eur J Hum Genet. 2011 Jul;19(7):807-12. (PMID: 21407268)
      PLoS Genet. 2010 Aug 12;6(8):null. (PMID: 20714348)
      Nature. 2015 Feb 12;518(7538):197-206. (PMID: 25673413)
      Int J Cardiol. 2016 Mar 1;206:129-30. (PMID: 26788688)
      PLoS One. 2014 Apr 09;9(4):e93766. (PMID: 24718290)
      Kardiol Pol. 2013;71(9):931-6. (PMID: 24065422)
      Int J Epidemiol. 2015 Apr;44(2):512-25. (PMID: 26050253)
      Nat Rev Genet. 2007 Oct;8(10):749-61. (PMID: 17726481)
    • Grant Information:
      United Kingdom Wellcome Trust; MC_QA137853 United Kingdom MRC_ Medical Research Council; MR/M005070/1 United Kingdom MRC_ Medical Research Council; MR/M023095/1 United Kingdom MRC_ Medical Research Council
    • Publication Date:
      Date Created: 20170929 Date Completed: 20171016 Latest Revision: 20220129
    • Publication Date:
      20240105
    • Accession Number:
      PMC5619771
    • Accession Number:
      10.1371/journal.pone.0185083
    • Accession Number:
      28957414