eprintid: 1557447
rev_number: 41
eprint_status: archive
userid: 608
dir: disk0/01/55/74/47
datestamp: 2017-05-28 06:05:33
lastmod: 2022-01-16 23:53:06
status_changed: 2017-06-29 10:10:56
type: article
metadata_visibility: show
creators_name: Iglesias, AI
creators_name: van der Lee, SJ
creators_name: Bonnemaijer, PWM
creators_name: Höhn, R
creators_name: Nag, A
creators_name: Gharahkhani, P
creators_name: Khawaja, AP
creators_name: Broer, L
creators_name: International Glaucoma Genetics Consortium (IGGC), .
creators_name: Foster, PJ
creators_name: Hammond, CJ
creators_name: Hysi, PG
creators_name: van Leeuwen, EM
creators_name: MacGregor, S
creators_name: Mackey, DA
creators_name: Mazur, J
creators_name: Nickels, S
creators_name: Uitterlinden, AG
creators_name: Klaver, CCW
creators_name: Amin, N
creators_name: van Duijn, CM
title: Haplotype reference consortium panel: Practical implications of imputations with large reference panels
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D08
divisions: D13
keywords: association studies;
imputation;
1000 Genomes Project reference panel;
Haplotype Reference Consortium;
vertical cup-disc ratio
note: Copyright © 2017 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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.
date: 2017-08
date_type: published
official_url: http://dx.doi.org/10.1002/humu.23247
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1294744
doi: 10.1002/humu.23247
lyricists_name: Foster, Paul
lyricists_name: Hysi, Pirro
lyricists_name: Khawaja, Anthony
lyricists_id: PJFOS52
lyricists_id: PHYSI17
lyricists_id: APKHA37
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Human Mutation
volume: 38
number: 8
pagerange: 1025-1032
event_location: United States
issn: 1098-1004
citation:        Iglesias, AI;    van der Lee, SJ;    Bonnemaijer, PWM;    Höhn, R;    Nag, A;    Gharahkhani, P;    Khawaja, AP;                                                         ... van Duijn, CM; + view all <#>        Iglesias, AI;  van der Lee, SJ;  Bonnemaijer, PWM;  Höhn, R;  Nag, A;  Gharahkhani, P;  Khawaja, AP;  Broer, L;  International Glaucoma Genetics Consortium (IGGC), .;  Foster, PJ;  Hammond, CJ;  Hysi, PG;  van Leeuwen, EM;  MacGregor, S;  Mackey, DA;  Mazur, J;  Nickels, S;  Uitterlinden, AG;  Klaver, CCW;  Amin, N;  van Duijn, CM;   - view fewer <#>    (2017)    Haplotype reference consortium panel: Practical implications of imputations with large reference panels.                   Human Mutation , 38  (8)   pp. 1025-1032.    10.1002/humu.23247 <https://doi.org/10.1002/humu.23247>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1557447/1/Iglesias_Haplotype_reference_consortium.pdf