Advances in haplotype phasing and genotype imputation

Quan Sun; Yun Li

doi:10.1038/s41576-025-00895-2

Advances in haplotype phasing and genotype imputation

Nat Rev Genet. 2026 Feb;27(2):155-169. doi: 10.1038/s41576-025-00895-2. Epub 2025 Sep 24.

Authors

Quan Sun^{1

2}, Yun Li^{3

4}

Affiliations

¹ Center for Computational and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
² Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. yunli@med.unc.edu.
⁴ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. yunli@med.unc.edu.

PMID: 40993437
DOI: 10.1038/s41576-025-00895-2

Abstract

Haplotype phasing - to determine which genetic variants reside on the same chromosome - and genotype imputation - to infer unobserved genotypes - have become indispensable steps to improve genome coverage for genomic analyses such as genome-wide association studies. Several tools exist for haplotype phasing and genotype imputation, all of which have continuously evolved to accommodate the increasing sample sizes of genomic studies and rapidly improving sequencing technologies. To fully leverage these recent advances, researchers must deliberate several practical considerations, including tool choice, quality control filters, data privacy concerns and reference panel choice. Looking ahead, long-read sequencing technologies are poised to bring novel opportunities to this field and drive methodological development.

Publication types

Review

MeSH terms

Genome-Wide Association Study* / methods
Genomics / methods
Genotype*
Haplotypes* / genetics
High-Throughput Nucleotide Sequencing / methods
Humans
Polymorphism, Single Nucleotide