Population-specific reference panel improves imputation quality for genome-wide association studies conducted on the Japanese population

To improve imputation quality for genome-wide association studies (GWAS) conducted on the Japanese population, we developed and evaluated four Japanese population-specific reference panels. These panels were constructed through the augmentation of the 1000 Genomes Project (1KG) panel using Japanese whole genome sequencing (WGS) data, with sample sizes ranging from 1 K to 7 K individuals enrolled through the Biobank Japan (BBJ) project, and sequencing depths ranging from 3× to 30×. Among these panels, an augmented reference panel comprising 7472 WGS samples of mixed depth (1KG+7K) exhibit the greatest improvement in imputation quality relative to the Trans-Omics for Precision Medicine (TOPMed) reference panel. Notably, we observe these improvements primarily for rare variants with a minor allele frequency (MAF) <5%. To demonstrate the benefits of improved imputation quality in association analyses of complex traits, we conducted GWAS for serum uric acid and total cholesterol levels following imputation up to the 1KG+7K panel. The analysis reveals several loci reaching genome-wide significance (P < 5 × 10<sup>-8</sup>) in the 1KG+7K imputation output yet remaining undetected when the same sample set is imputed up to the TOPMed reference panel. In summary, the 1KG+7K panel demonstrates significant advantages in the discovery of trait-associated loci, particularly those influenced by low-frequency association signals.

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Publication Details

Journal
Communications Biology
Published
2024-12-19
DOI
https://doi.org/10.1038/s42003-024-07338-4
Citations
13
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
7.15

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Population-specific reference panel improves imputation quality for genome-wide association studies conducted on the Japanese population

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Communications Biology
Genetic Associations and Epidemiology
7.15
article

Population-specific reference panel improves imputation quality for genome-wide association studies conducted on the Japanese population

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article en
13 citations

Abstract

To improve imputation quality for genome-wide association studies (GWAS) conducted on the Japanese population, we developed and evaluated four Japanese population-specific reference panels. These panels were constructed through the augmentation of the 1000 Genomes Project (1KG) panel using Japanese whole genome sequencing (WGS) data, with sample sizes ranging from 1 K to 7 K individuals enrolled through the Biobank Japan (BBJ) project, and sequencing depths ranging from 3× to 30×. Among these panels, an augmented reference panel comprising 7472 WGS samples of mixed depth (1KG+7K) exhibit the greatest improvement in imputation quality relative to the Trans-Omics for Precision Medicine (TOPMed) reference panel. Notably, we observe these improvements primarily for rare variants with a minor allele frequency (MAF) <5%. To demonstrate the benefits of improved imputation quality in association analyses of complex traits, we conducted GWAS for serum uric acid and total cholesterol levels following imputation up to the 1KG+7K panel. The analysis reveals several loci reaching genome-wide significance (P < 5 × 10<sup>-8</sup>) in the 1KG+7K imputation output yet remaining undetected when the same sample set is imputed up to the TOPMed reference panel. In summary, the 1KG+7K panel demonstrates significant advantages in the discovery of trait-associated loci, particularly those influenced by low-frequency association signals.

Communications BiologyVol. 7(1)
Nihon University (JP), National Institute of Genetics (JP), University of North Carolina at Chapel Hill (US), Kyushu University (JP), Seoul National University (KR), University of Liverpool (GB), University of Shizuoka (JP), Shiga University of Medical Science (JP), Iwate Medical University (JP), The Graduate University for Advanced Studies, SOKENDAI (JP), University of Manchester (GB), Juntendo University (JP), Osaka National Hospital (JP), Fukuoka Tokushukai Hospital (JP), Japan Anti Tuberculosis Association (JP), University of Tokyo Hospital (JP), Arthritis UK (GB), Shizuoka General Hospital (JP), The Cancer Institute Hospital (JP), Aso Iizuka Hospital (JP), RIKEN Center for Integrative Medical Sciences (JP), Osaka International Cancer Institute (JP), Tokyo Metropolitan Geriatric Hospital (JP), Fukujuji Hospital (JP), Japanese Foundation For Cancer Research (JP), The University of Tokyo (JP), Nippon Medical School (JP)
Japan Agency for Medical Research and Development, National Research Foundation, National Research Foundation of Korea, Ministry of Science and ICT, South Korea, Japan Society for the Promotion of Science, RIKEN
Openalex Percentile: Top 3%
Genetic Associations and Epidemiology
7.15
DOIOpen Access PDFOpenAlex
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