Haplotype reference consortium panel: Practical implications of imputations with large reference panels.

Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and HRC imputations. We compared the results of the meta-analysis using 1000GP to the meta-analysis results using HRC. Overall, we found that using HRC imputation significantly improved P values (P = 3.07 × 10-61 ), particularly for suggestive variants. Both meta-analyses were performed in the same sample size, yet we found eight genome-wide significant loci in the HRC-based meta-analysis versus seven genome-wide significant loci in the 1000GP-based meta-analysis. This study provides supporting evidence of the new avenues for gene discovery and fine mapping that the HRC imputation panel offers.

Variability of vertical cup to disc ratio measurement and the effects of glaucoma 5-year risk estimation in untreated ocular hypertensive eyes.

AIM: To compare the vertical cup to disc ratio (VCDR) measurements obtained with optical coherence tomography (OCT), Heidelberg retina tomography (HRT) and stereophotography of the optic nerve head (ONH) in patients with ocular hypertension (OHT), and their corresponding estimated 5-year risk for development of glaucoma. METHODS: ONH images of patients with OHT were taken by fundus camera (stereoscopic images), OCT and HRT. Optic disc stereophotographs were evaluated with a stereo-viewer by two glaucoma specialists (SP1 and SP2) and the VCDR was measured with the ImageJ software. VCDR measurements obtained with stereophotography, OCT and HRT were used to calculate the estimated 5-year risk. RESULTS: One hundred and forty eyes of 75 patients with OHT were included. The VCDR values measured by OCT, HRT, SP1 and SP2 were 0.60±0.14, 0.53±0.23, 0.44±0.13 and 0.49±0.10, respectively. The corresponding 5-year risk for development of glaucoma was 19.54%±16.60%, 18.13%±16.96%, 15.64%±14.35% and 16.70%±14.49%, respectively. Different degrees of proportional biases were observed in VCDR measurements obtained with stereophotography, OCT and HRT. The maximum difference of VCDR measurement was 0.64, while the maximum difference of the corresponding 5-year risk was 24.02%. CONCLUSION: The disagreement in VCDR measured by OCT, HRT and stereophotography in untreated OHT eyes extends to their 5-year risk estimation of glaucoma development.

Association between polymorphism of optic disc related genes and susceptibility to primary open angle glaucoma in Inner Mongolia / 中华实验眼科杂志

Objective To evaluate the association between polymorphism of the optic disc related genes and primary open angle glaucoma (POAG) in Inner Mongolia.Methods A retrospective study was adopted.Pathography on 108 POAG patients was collected from six hospitals in Hohhot,Baotou city from January,2014 to December,2016 as POAG group.At the same time,120 healthy persons were included as the control group.Fasting venous blood of 2 ml blood was collected by EDTA anticoagulant.Mass spectrometry was used to genotype the single nucleotide polymorphism (SNPs) of RFTN1 (rs690037),ATOH7 (rs7916697,rs3858145),CDC7 (rs1192415),CDKN2B (rs1063192) and SIX (rs10483727) in 108 patients with POAG and 120 normal controls.The association of gene polymorphism with POAG was analyzed by the x2 test and logistic regression analysis.The study protocol was approved by the Ethics Committee of Inner Mongolia Baogang Hospital,and written informed consent was obtained from each patient.Results The frequency of CDKN2B (rs1063192) G allele in the POAG group was significantly higher than that in the control group (27％ VS.17％,odds ratio[OR] =1.824,95％ confidence interval [CI]:1.163-2.861,P=0.008),whereas allele frequencies of the other 7 SNPs were not statistically different between the two groups (all at P＞ 0.05).Additive and dominant models of rs1063192 indicated that the individual with G allele was more likely to suffer from POAG,with a significant difference (P＜0.05),but A allele did not significantly reduce the risk of POAG (P＞0.05).There was no significant difference in the distribution of other SNPs genotypes between the POAG group and the control group (P＞0.05).Conclusions The polymorphism of CDKN2B (rs1063192) is associated with the susceptibility to POAG,and the minor G allele may increase the risk of POAG.