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

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 

机构地区：[1]Ministry of Education Key Laboratory of Environment and Health,School of Public Health,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Department of Epidemiology and Biostatistics,School of Public Health,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [3]Centre for Precision Health,Edith Cowan University,Perth,WA 6027,Australia [4]Collaborative Genomics and Translation Group,School of Medical and Health Sciences,Edith Cowan University,Perth,WA 6027,Australia [5]Curtin Medical School,Bentley,WA 6102,Australia [6]The Florey Institute of Neuroscience and Mental Health,University of Melbourne,Melbourne,VIC 3052,Australia [7]Department of Occupational and Environmental Health,School of Public Health,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Genomics, Proteomics & Bioinformatics》2024年第3期43-54,共12页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Grant Nos.82325044 and 82021005);the China Postdoctoral Science Foundation(Grant No.2021M701318);the Natural Science Fund for Distinguished Young Scholars of Hubei Province,China(Grant No.2022CFA046);the Fundamental Research Funds for the Central Universities,China(Grant Nos.2019kfyXJJS036 and 2023BR030 of HUST);funded by the National Health and Medical Research Council in Australia(Grant Nos.GNT1161706 and GNT1151854).

摘　　要：Epigenome-wide association studies(EWAS)are susceptible to widespread confounding caused by population structure and genetic relatedness.Nevertheless,kinship estimation is challenging in EWAS without genotyping data.Here,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 microarrays.We 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 algorithm.We conducted extensive simulations to demonstrate the performance of the method.When 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 relatedness.Furthermore,we showed that MethylGenotyper allows for the estimation of both population structure and cryptic relatedness among 702 Australians of diverse ancestry.We also implemented MethylGenotyper in a publicly available R package(https://github.com/Yi-Jiang/MethylGenotyper)to facilitate future large-scale EWAS.

关 键 词：DNA methylation Genotype calling Genetic relatedness Population structure Epigenome-wide association study 

分 类 号：Q953[生物学—动物学]