eCite Digital Repository

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


Iglesias, AI and van der Lee, SJ and Bonnemaijer, PWM and Hohn, R and Nag, A and Gharahkhani, P and Khawaja, AP and Broer, L and Foster, PJ and Hammond, CJ and Hysi, PG and van Leeuwen, EM and MacGregor, S and Mackey, DA and Mazur, J and Nickels, S and Uitterlinden, AG and Klaver, CCW and Amin, N and van Duijn, CM, International Glaucoma Genetics Consortium (IGGC), Haplotype reference consortium panel: Practical implications of imputations with large reference panels, Human Mutation, 38, (8) pp. 1025-1032. ISSN 1059-7794 (2017) [Refereed Article]

Copyright Statement

Copyright 2017 The Authors

DOI: doi:10.1002/humu.23247


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 (= 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.

Item Details

Item Type:Refereed Article
Keywords:1000 Genomes Project reference panel, Haplotype Reference Consortium, association studies, imputation, vertical cup-disc ratio
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:124278
Year Published:2017
Web of Science® Times Cited:21
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-02-16
Last Modified:2018-06-05

Repository Staff Only: item control page