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

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.

SUBMITTER: Pilling LC

PROVIDER: S-EPMC5619771 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Pilling Luke C LC Atkins Janice L JL Duff Michael O MO Beaumont Robin N RN Jones Samuel E SE Tyrrell Jessica J Kuo Chia-Ling CL Ruth Katherine S KS Tuke Marcus A MA Yaghootkar Hanieh H Wood Andrew R AR Murray Anna A Weedon Michael N MN Harries Lorna W LW Kuchel George A GA Ferrucci Luigi L Frayling Timothy M TM Melzer David D

PloS one 20170928 9

<h4>Introduction</h4>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.<h4>Results</h4>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 signa ...[more]

PMID: 28957414

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Project description:BackgroundHigher red blood cell distribution width (RDW) levels are associated with mortality in patients with chronic obstructive pulmonary disease (COPD). However, more convincing evidence is still lacking, and the relationship between hemoglobin-to-red blood cell distribution width ratio (HRR) and mortality in patients with COPD remains unclear.MethodsThis study is a prospective cohort study that includes 3,745 adult patients with COPD from the National Health and Nutrition Examination Survey (NHANES) database spanning from 1999 to 2018 in the United States. COX proportional hazards regression analysis, Kaplan-Meier survival curves and restricted cubic spline models were employed to investigate the association of RDW and HRR levels with mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of RDW and HRR in predicting mortality in patients with COPD.ResultsHigher RDW level was positively associated with increased risk of all-cause mortality (HR = 1.16, 95% CI = 1.11-1.21, P < 0.001), cardiovascular disease (CVD) mortality (HR = 1.13, 95% CI = 1.06-1.21, P < 0.001), and chronic lower respiratory disease (CLRD) related mortality (HR = 1.15, 95% CI = 1.05-1.25, P = 0.003) after adjusting for various potential confounders. HRR was inversely associated with all-cause mortality (HR = 0.14, 95% CI = 0.08-0.25, P < 0.001), CVD mortality (HR = 0.12, 95% CI = 0.05-0.31, P < 0.001). HRR has no significant correlation with CLRD-related mortality. The time-dependent ROC curve showed that RDW exhibited area under the curves (AUCs) of the 5- and 10-year survival rates were 0.707 and 0.714 for all-cause mortality and 0.686 and 0.698, respectively, for CVD mortality. HRR yielded AUCs of the 5- and 10-year survival rates were 0.661 and 0.653 for all-cause mortality and 0.654 and 0.66, respectively, for CVD mortality.ConclusionHigher RDW levels were positively associated with an increased risk of mortality in patients with COPD. HRR levels were negatively correlated with the risk of all-cause and CVD mortality. The predictive value of HRR for mortality in these patients is lower than that of RDW.

Project description:BackgroundLung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. Inflammation has been proven to be one of the characteristics of malignant tumors. Chronic inflammatory response mediated by cytokines in the tumor microenvironment is an important factor in tumorigenesis. The purpose of this study was to observe and evaluate the value of red blood cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and hemoglobin-to-red blood cell distribution width ratio (HRR) in the progression of NSCLC.MethodsA total of 245 patients with NSCLC, 97 patients with benign pulmonary nodules, and 94 healthy volunteers were included in this study. Factors, such as age, gender, smoking history, histological type, lymph node metastasis, distant metastasis, TNM stage, and differentiation degree were statistically analyzed. The correlation of RDW, NLR, and HRR of patients with NSCLC with other clinical experimental parameters were also analyzed. Then, the diagnostic value of RDW, NLR, and HRR in the progression of NSCLC was evaluated.ResultsRDW, NLR, and HRR could be used to distinguish patients with NSCLC from healthy controls (p < 0.05). In addition, only the RDW in the NSCLC group with III-IV stage was significantly different from that in the benign pulmonary nodules group (p = 0.033), while NLR and HRR could significantly distinguish patients with NSCLC and benign pulmonary nodules (p < 0.001). RDW and NLR were positively correlated with NSCLC stage, whereas HRR was negatively correlated with NSCLC stage. RDW, NLR, and HRR were also significantly associated with the differentiation degree of NSCLC (p < 0.05). The ROC curve analysis showed that the combination of RDW with NLR, HRR, and CEA could show significantly higher diagnostic value than any one marker alone (AUC = 0.925, 95% CI: 0.897-0.954, and sensitivity and specificity of 79.60% and 93.60%, respectively).ConclusionRDW, NLR, and HRR can be utilized as simple and effective biomarkers for the diagnosis and evaluation of NSCLC progression.

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

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

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