A Genomics England haplotype reference panel and imputation of UK Biobank

作者：Sinan Shi, Simone Rubinacci, Sile Hu, Loukas Moutsianas, Alexander Stuckey, Anna C. Need, Pier Francesco Palamara, Mark J. Caulfield, Jonathan Marchini, Simon Myers · 发表于：Nature Genetics · 年份：2024 · DOI：10.1038/s41588-024-01868-7 · 被引用次数：32 · 研究领域：Genetic Associations and Epidemiology、Genomics and Rare Diseases、Genetic Syndromes and Imprinting

Abstract We built a reference panel with 342 million autosomal variants using 78,195 individuals from the Genomics England (GEL) dataset, achieving a phasing switch error rate of 0.18% for European samples and imputation quality of r 2 = 0.75 for variants with minor allele frequencies as low as 2 × 10 −4 in white British samples. The GEL-imputed UK Biobank genome-wide association analysis identified 70% of associations found by direct exome sequencing ( P < 2.18 × 10 −11 ), while extending testing of rare variants to the entire genome. Coding variants dominated the rare-variant genome-wide association results, implying less disruptive effects of rare non-coding variants.