Journal
HUMAN MUTATION
Volume 38, Issue 8, Pages 1025-1032Publisher
WILEY-HINDAWI
DOI: 10.1002/humu.23247
Keywords
association studies; imputation; 1000 Genomes Project reference panel; Haplotype Reference Consortium; vertical cup-disc ratio
Categories
Funding
- Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands
- Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission
- Municipality of Rotterdam
- Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]
- Genetic Laboratory of the Department of Internal Medicine, Erasmus MC
- Research Institute for Diseases in the Elderly [014-93-015]
- Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]
- Genetic Laboratory of the Department of Internal Medicine
- Department of Forensic Molecular Biology
- Department of Dermatology, Erasmus MC, Rotterdam, the Netherlands
- European Commission FP6 STRP [018947, LSHG-CT-2006-01947]
- European Community's Seventh Framework Programme (FP7)
- European Commission under the program 'Quality of Life and Management of the Living Resources' of the 5th Framework Programme [HEALTH-F4-2007-201413, QLG2-CT-2002-01254]
- Stichting Lijf en Leven
- Stichting Oogfonds Nederland
- Landelijke Stichting voor Blinden en Slechtzienden
- Algemene Nederlandse Vereniging ter Voorkoming van Blindheid
- Medical Workshop
- Heidelberg Engineering
- Topcon Europe BV
- Australian Research Council Future Fellowship
- National Institute of Health (NIH), National Eye Institute (NEI) [1 R01 EY024233-03]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available