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

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

DOI：
10.1002/humu.23247
复制
发表时间：
2017-08-01
期刊：
HUMAN MUTATION
影响因子：
3.9
通讯作者：
van Duijn, Cornelia M.
van Duijn, Cornelia M.
中科院分区：
医学2区
文献类型：
--
作者：
Iglesias, Adriana I.;van der Lee, Sven J.;van Duijn, Cornelia M.

文献摘要

被引文献

相似文献

最近，Haplotype Reference Consortium（HRC）发布了一个大型插补面板，可以更准确地插补遗传变异。在这项研究中，我们比较了一组直接测定的常见和罕见变异的外显子组阵列的插补基因型，即1000基因组计划（1000 GP）和HRC。我们发现，使用HRC面板的插补提高了常见的，特别是低频变异的测定和插补基因型之间的一致性。此外，我们在四个队列中使用1000 GP和HRC插补对垂直杯盘比（青光眼的高度遗传性内表型）进行了全基因组关联荟萃分析。我们将使用1000 GP的荟萃分析结果与使用HRC的荟萃分析结果进行了比较。总体而言，我们发现使用HRC插补显著改善了P值（P=3.07x10（-61）），特别是对于提示性变异。两项荟萃分析均在相同的样本量下进行，但我们在基于HRC的荟萃分析中发现了8个全基因组显著性位点，而在基于1000 GP的荟萃分析中发现了7个全基因组显著性位点。这项研究提供了支持的证据，新途径的基因发现和精细定位，人权理事会插补小组提供。
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=3.07x10(-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.