TY - JOUR
T1 - Haplotype reference consortium panel
T2 - Practical implications of imputations with large reference panels
AU - International Glaucoma Genetics Consortium (IGGC)
AU - Iglesias, Adriana I.
AU - van der Lee, Sven J.
AU - Bonnemaijer, Pieter W.M.
AU - Höhn, René
AU - Nag, Abhishek
AU - Gharahkhani, Puya
AU - Khawaja, Anthony P.
AU - Broer, Linda
AU - Foster, Paul J.
AU - Hammond, Christopher J.
AU - Hysi, Pirro G.
AU - van Leeuwen, Elisabeth M.
AU - MacGregor, Stuart
AU - Mackey, David A.
AU - Mazur, Johanna
AU - Nickels, Stefan
AU - Uitterlinden, André G.
AU - Klaver, Caroline C.W.
AU - Amin, Najaf
AU - van Duijn, Cornelia M.
N1 - Publisher Copyright:
© 2017 The Authors. Human Mutation Published by Wiley Periodicals, Inc.
PY - 2017/8
Y1 - 2017/8
N2 - 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.
AB - 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.
KW - 1000 Genomes Project reference panel
KW - association studies
KW - Haplotype Reference Consortium
KW - imputation
KW - vertical cup-disc ratio
UR - http://www.scopus.com/inward/record.url?scp=85020417516&partnerID=8YFLogxK
U2 - 10.1002/humu.23247
DO - 10.1002/humu.23247
M3 - Article
C2 - 28493391
AN - SCOPUS:85020417516
SN - 1059-7794
VL - 38
SP - 1025
EP - 1032
JO - Human Mutation
JF - Human Mutation
IS - 8
ER -