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RESEARCH PRODUCT
Haplotype reference consortium panel: Practical implications of imputations with large reference panels.
Adriana I IglesiasSven J Van Der LeePieter W M BonnemaijerRené HöhnAbhishek NagPuya GharahkhaniAnthony P KhawajaLinda BroerGlaucoma Genetics Consortium (Iggc) InternationalPaul J FosterChristopher J HammondPirro G. HysiElisabeth M Van LeeuwenStuart MacgregorDavid A MackeyJohanna MazurStefan NickelsAndré G UitterlindenCaroline C W KlaverNajaf AminCornelia M. Van Duijnsubject
0301 basic medicineGenotypeConcordanceGenome-wide association study610 Medicine & healthBiologyPolymorphism Single NucleotideSensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]03 medical and health sciencesGene FrequencyGeneticsAssociation studies Imputation 1000 Genomes Project reference Panel Haplotype Reference Consortium Vertical cup-disc ratioHumansExome1000 Genomes Project610 Medicine & healthExomeAllele frequencyGenetics (clinical)Genetic associationGeneticsGenome HumanHaplotypeGenetic Variation030104 developmental biologyHaplotypesImputation (genetics)Genome-Wide Association Studydescription
Contains fulltext : 177754.pdf (Publisher’s version ) (Open Access) 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 x 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-06-09 |