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