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

Jiayi Xu; Dongjing Liu; Arsalan Hassan; Giulio Genovese; Alanna C Cote; Brian Fennessy; Esther Cheng; Alexander W Charney; James A Knowles; Muhammad Ayub; Roseann E Peterson; Tim B Bigdeli; Laura M Huckins

doi:10.1101/2023.12.22.23300448

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

medRxiv [Preprint]. 2023 Dec 26:2023.12.22.23300448. doi: 10.1101/2023.12.22.23300448.

Authors

Jiayi Xu¹, Dongjing Liu², Arsalan Hassan^{3

4}, Giulio Genovese^{5

6

7}, Alanna C Cote², Brian Fennessy², Esther Cheng², Alexander W Charney², James A Knowles⁸, Muhammad Ayub⁹, Roseann E Peterson¹⁰, Tim B Bigdeli¹⁰, Laura M Huckins¹

Affiliations

¹ Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
² Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³ University of Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan.
⁴ Institute of Omics and Health Research, Lahore, Pakistan.
⁵ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Stanley Center, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁷ Department of Genetics, Harvard Medical School, Boston, MA, USA.
⁸ The Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA.
⁹ University College London, London, UK.
¹⁰ Department of Psychiatry and Behavioral Sciences, Institute for Genomics in Health, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA.

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.

Keywords: Genetics; Genome-Wide Association Studies; Imputation; Imputation Panels; Pakistan; South Asian Ancestry.

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Preprint

Abstract

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