Dataset Information

Evaluation of imputation performance of multiple reference panels in a Pakistani population.

ABSTRACT: Genotype imputation is crucial for GWAS, but reference panels and existing benchmarking studies prioritize European individuals. Consequently, it is unclear which publicly available reference panel should be used for Pakistani individuals, and whether ancestry composition or sample size of the panel matters more for imputation accuracy. Our study compared different reference panels to impute genotype data in 1814 Pakistani individuals, finding the best performance balancing accuracy and coverage with meta-imputation with TOPMed and the expanded 1000 Genomes (ex1KG) reference. Imputation accuracy of ex1KG outperformed TOPMed despite its 30-fold smaller sample size, supporting efforts to create future panels with diverse populations.

SUBMITTER: Xu J

PROVIDER: S-EPMC10793543 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Evaluation of imputation performance of multiple reference panels in a Pakistani population.

Xu Jiayi J Liu Dongjing D Hassan Arsalan A Genovese Giulio G Cote Alanna C AC Fennessy Brian B Cheng Esther E Charney Alexander W AW Knowles James A JA Ayub Muhammad M Peterson Roseann E RE Bigdeli Tim B TB Huckins Laura M LM

medRxiv : the preprint server for health sciences 20231226

Genotype imputation is crucial for GWAS, but reference panels and existing benchmarking studies prioritize European individuals. Consequently, it is unclear which publicly available reference panel should be used for Pakistani individuals, and whether ancestry composition or sample size of the panel matters more for imputation accuracy. Our study compared different reference panels to impute genotype data in 1814 Pakistani individuals, finding the best performance balancing accuracy and coverage ...[more]

PMID: 38234809

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Project description:Imputation servers offer the exclusive possibility to harness the largest public reference panels which have been shown to deliver very high precision in the imputation of European genomes. Many studies have nonetheless stressed the importance of 'study specific panels' (SSPs) as an alternative and have shown the benefits of combining public reference panels with SSPs. But such combined approaches are not attainable when using external imputation servers. To investigate how to confront this challenge, we imputed 550 French individuals using either the University of Michigan imputation server with the Haplotype Reference Consortium (HRC) panel or an in-house SSP of 850 whole-genome sequenced French individuals. With approximate geo-localization of both our target and SSP individuals we are able to pinpoint different scenarios where SSP-based imputation would be preferred over server-based imputation or vice-versa. This is achieved by showing to a high degree of resolution the importance of the proximity of the reference panel to target individuals; with a focus on the clear added value of SSPs for estimating haplotype phase and for the imputation of rare variants (minor allele-frequency below 0.01). Such benefits were most evident for individuals from the same geographical regions in France as the SSP individuals. Overall, only 42.3% of all 125,442 variants evaluated were better imputed with an SSP from France compared to an external reference panel, however this rises to 58.1% for individuals from geographic regions well covered by the SSP. By investigating haplotype sharing and population fine-structure in France, we show the importance of including SSP haplotypes for imputation but also that they should ideally be combined with large public panels. In the absence of the unattainable results from a combined panel of the HRC and our French SSP, we put forward a pragmatic solution where server-based and SSP-based imputation outcomes can be combined based on comparing posterior genotype probabilities. We show that such an approach can give a level of imputation accuracy in excess of what could be achieved with either strategy alone. The results presented provide detailed insights into the accuracy of imputation that should be expected from different strategies for European populations.

Dataset Information

Evaluation of imputation performance of multiple reference panels in a Pakistani population.

Publications

Evaluation of imputation performance of multiple reference panels in a Pakistani population.

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