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MethylGenotyper:Accurate Estimation of SNP Genotypes and Genetic Relatedness from DNA Methylation Data

Genomics, Proteomics & Bioinformatics 2024年第3期22卷 43-54页

作者： Yi Jiang Minghan Qu Minghui Jiang Xuan Jiang Shane Fernandez tenielle porter Simon M.Laws Colin L.Masters Huan Guo Shanshan Cheng Chaolong Wang Ministry of Education Key Laboratory of Environment and Health School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Centre for Precision Health Edith Cowan UniversityPerthWA 6027Australia Collaborative Genomics and Translation Group School of Medical and Health SciencesEdith Cowan UniversityPerthWA 6027Australia Curtin Medical School BentleyWA 6102Australia The Florey Institute of Neuroscience and Mental Health University of MelbourneMelbourneVIC 3052Australia Department of Occupational and Environmental Health School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Epigenome-wide association studies(EWAS)are susceptible to widespread confounding caused by population structure and genetic ***,kinship estimation is challenging in EWAS without genotyping ***,we proposed MethylGenotyper,a method that for the first time enables accurate genotyping at thousands of single nucleotide polymorphisms(SNPs)directly from commercial DNA methylation *** modeled the intensities of methylation probes near SNPs with a mixture of three beta distributions corresponding to different genotypes and estimated parameters with an expectation-maximization *** conducted extensive simulations to demonstrate the performance of the *** applying MethylGenotyper to the Infinium EPIC array data of 4662 Chinese samples,we obtained genotypes at 4319 SNPs with a concordance rate of 98.26%,enabling the identification of 255 pairs of close ***,we showed that MethylGenotyper allows for the estimation of both population structure and cryptic relatedness among 702 Australians of diverse *** also implemented MethylGenotyper in a publicly available R package(https://***/Yi-Jiang/MethylGenotyper)to facilitate future large-scale EWAS.

关键词： DNA methylation Genotype calling Genetic relatedness Population structure Epigenome-wide association study

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