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Haplotype reference consortium panel: Practical implications of imputations with large reference panels
Author(s) -
Iglesias Adriana I.,
der Lee Sven J.,
Bonnemaijer Pieter W.M.,
Höhn René,
Nag Abhishek,
Gharahkhani Puya,
Khawaja Anthony P.,
Broer Linda,
Foster Paul J.,
Hammond Christopher J.,
Hysi Pirro G.,
Leeuwen Elisabeth M.,
MacGregor Stuart,
Mackey David A.,
Mazur Johanna,
Nickels Stefan,
Uitterlinden André G.,
Klaver Caroline C.W.,
Amin Najaf,
Duijn Cornelia M.
Publication year - 2017
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23247
Subject(s) - imputation (statistics) , biology , concordance , 1000 genomes project , genome wide association study , meta analysis , haplotype , genetics , genome , genetic association , computational biology , genotype , missing data , single nucleotide polymorphism , statistics , gene , medicine , mathematics
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.