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2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio.

ABSTRACT: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are important biomarkers for disease development and progression. To gain insight into the genetic causes of variance in NLR and PLR in the general population, we conducted genome-wide association (GWA) analyses and estimated SNP heritability in a sample of 5901 related healthy Dutch individuals. GWA analyses identified a new genome-wide significant locus on the HBS1L-MYB intergenic region for PLR, which replicated in a sample of 2538 British twins. For platelet count, we replicated three known genome-wide significant loci in our cohort (at CCDC71L-PIK3CG, BAK1 and ARHGEF3). For neutrophil count, we replicated the PSMD3 locus. For the identified top SNPs, we found significant cis and trans expression quantitative trait loci effects for several loci involved in hematological and immunological pathways. Linkage Disequilibrium score (LD) regression analyses for PLR and NLR confirmed that both traits are heritable, with a polygenetic SNP heritability for PLR of 14.1%, and for NLR of 2.4%. Genetic correlations were present between ratios and the constituent counts, with the genetic correlation (r=0.45) of PLR with platelet count reaching statistical significance. In conclusion, we established that two important biomarkers have a significant heritable SNP component, and identified the first genome-wide locus for PLR.

SUBMITTER: Lin BD

PROVIDER: S-EPMC5669488 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio.

Lin Bochao Danae BD Carnero-Montoro Elena E Bell Jordana T JT Boomsma Dorret I DI de Geus Eco J EJ Jansen Rick R Kluft Cornelis C Mangino Massimo M Penninx Brenda B Spector Tim D TD Willemsen Gonneke G Hottenga Jouke-Jan JJ

Journal of human genetics 20170803 11

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are important biomarkers for disease development and progression. To gain insight into the genetic causes of variance in NLR and PLR in the general population, we conducted genome-wide association (GWA) analyses and estimated SNP heritability in a sample of 5901 related healthy Dutch individuals. GWA analyses identified a new genome-wide significant locus on the HBS1L-MYB intergenic region for PLR, which replicated in a ...[more]

PMID: 29066854

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Project description:BackgroundThe preoperative peripheral blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have been reported to be associated with the prognosis of various cancers but are always discussed separately. The aim of this study is to bring the combination of NLR, PLR and MLR into the prognostic assessment system of endometrial cancer (EC) and establish a nomogram to provide an objective prediction model for clinical decisions.MethodsA total of 1111 patients with EC who had accepted surgical treatment during 2013-2017 were involved in the analysis. Their NLR, PLR, and MLR levels were obtained from a routine blood examination within 2 weeks before operation. Receiver operating characteristic curve (ROC) analysis was performed to determine optimal cutoffs. Chi-square tests analysed the associations of the ratios with other clinicopathological variables. The prognostic value was indicated by overall survival (OS) via Cox proportional hazards models and Kaplan-Meier analysis. R software was used to establish the nomogram based on the combination of NLR, PLR, MLR and other clinicopathological factors.ResultsThe median follow-up period was 40 months, and the median age was 56. The enrolled patients were stratified by cutoffs of 2.14 for NLR, 131.82 for PLR and 0.22 for MLR. Multivariate analyses demonstrated that high NLR over 2.14 (HR = 2.71, 95%CI = 1.83-4.02, P<0.001), high PLR over 131.82 (HR = 2.75, 95%CI = 1.90-3.97, P<0.001), and high MLR over 0.22 (HR = 1.72, 95%CI = 1.20-2.45, P = 0.003) were significantly associated with worse OS. The combined indicator, high NLR + high PLR + high MLR (HR = 4.34, 95%CI = 2.54-7.42, P<0.001), showed the highest prognostic value. The Harrell's concordance index of the nomogram was 0.847 (95% CI = 0.804-0.890), showing good discrimination and calibration of this model.ConclusionThe combination of NLR, PLR, and MLR is a superior prognostic factor of EC. The nomogram involving the combination of NLR, PLR, MLR and other clinicopathological factors is recommended to predict OS for EC patients clinically.

Project description:BackgroundResearch on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in depression is still emerging and has increased 3-fold since the first meta-analysis. An updated meta-analysis with sufficient studies can provide more evidence for a potential relationship between NLR, PLR, MLR, and depression.MethodsWe identified 18 studies from the PubMed, EMBASE, Cochrane library, and Web of Science databases. Meta-analyses were performed to generate pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) between patients with depression and controls. Sensitivity analysis, subgroup analysis, meta-regression, and publication bias were conducted.ResultsA total of 18 studies including 2,264 depressed patients and 2,415 controls were included. Depressed patients had significantly higher NLR and PLR compared with controls (SMD = 0.33, 95% CI: 0.15-0.52, p < 0.001 and SMD = 0.24, 95% CI: 0.02-0.46, p < 0.05, respectively). MLR was slightly higher in depressed individuals compared to controls (SMD = 0.15, 95% CI: -0.26 to 0.55, p > 0.05), despite the absence of significance. Sensitivity analysis removing one study responsible for heterogeneity showed a higher and significant effect (SMD = 0.32, 95% CI: 0.20-0.44) of MLR. Three subgroup analyses of NLR, PLR, MLR, and depression revealed obvious differences in the inflammatory ratios between depressed patients and controls in China and the matched age and gender subgroup. Individuals with post-stroke depression (PSD) had higher NLR and MLR values as compared to non-PSD patients (SMD = 0.51, 95% CI: 0.36-0.67, p < 0.001 and SMD = 0.46, 95% CI: 0.12-0.79, p < 0.01, respectively). Meta-regression analyses showed that male proportion in the case group influenced the heterogeneity among studies that measured NLR values (p < 0.05).ConclusionsHigher inflammatory ratios, especially NLR, were significantly associated with an increased risk of depression. In the subgroup of China and matched age and gender, NLR, PLR, and MLR were all elevated in depressed patients vs. controls. Individuals with PSD had higher NLR and MLR values as compared to non-PSD patients. Gender differences may have an effect on NLR values in patients with depression.

Project description:BACKGROUND:Gastric cancer is the 2nd most common cause of cancer-related deaths, and the morbidity rate after surgery is reported to be as high as 46%. The estimation of possible complications, morbidity, and mortality and the ability to specify patients at high risk have become substantial for an intimate follow-up and for proper management in the intensive care unit. This study aimed to determine the prognostic value of the preoperative platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and their relations with clinical outcomes and complications after gastrectomy for gastric cancer. METHODS:This single-center, retrospective cohort study evaluated the data of 292 patients who underwent gastrectomy with curative intent between January 2015 and June 2018 in a tertiary state hospital in Ankara, Turkey. A receiver operating characteristic curve was generated to evaluate the ability of laboratory values to predict clinically relevant postoperative complications. The area under the curve was computed to compare the predictive power of the NLR and PLR. Then, the cutoff points were selected as the stratifying values for the PLR and NLR. RESULTS:The area under the curve values of the PLR (0.60, 95% CI 0.542-0.657) and NLR (0.556, 95% CI 0.497-0.614) were larger than those of the other preoperative laboratory values. For the PLR, the diagnostic sensitivity and specificity were 50.00 and 72.22%, respectively, whereas for the NLR, the diagnostic sensitivity and specificity were 37.50 and 80.16%, respectively. The PLR was related to morbidity, whereas the relation of the NLR with mortality was more prominent. This study demonstrated that the PLR and NLR may predict mortality and morbidity via the Clavien-Dindo classification in gastric cancer patients. The variable was grade ? 3 in the Clavien-Dindo classification, including complications requiring surgical or endoscopic interventions, life-threatening complications, and death. Both the PLR and NLR differed significantly according to Clavien-Dindo grade ? 3. In this analysis, the PLR was related to morbidity, while the NLR relation with mortality was more intense. CONCLUSION:Based on the results of the study, the PLR and NLR could be used as independent predictive factors for mortality and morbidity in patients with gastric cancer.

Dataset Information

2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio.

Publications

2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio.

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