Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Aug;38(8):1025-1032.
doi: 10.1002/humu.23247. Epub 2017 Jun 9.

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

Adriana I Iglesias  1   2 , Sven J van der Lee  1 , Pieter W M Bonnemaijer  1   2 , René Höhn  3   4 , Abhishek Nag  5 , Puya Gharahkhani  6 , Anthony P Khawaja  7   8 , Linda Broer  9 ; International Glaucoma Genetics Consortium (IGGC); Paul J Foster  8 , Christopher J Hammond  5 , Pirro G Hysi  5 , Elisabeth M van Leeuwen  2 , Stuart MacGregor  6 , David A Mackey  10   11 , Johanna Mazur  12 , Stefan Nickels  4 , André G Uitterlinden  1   9   13 , Caroline C W Klaver  1   2   14 , Najaf Amin  1 , Cornelia M van Duijn  1   15
Affiliations
Free article

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

Adriana I Iglesias et al. Hum Mutat. 2017 Aug.
Free article

Abstract

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.

Keywords: 1000 Genomes Project reference panel; Haplotype Reference Consortium; association studies; imputation; vertical cup-disc ratio.

PubMed Disclaimer

Publication types