Get started
Work

Random field modeling of multi-trait multi-locus association for detecting methylation quantitative trait loci

Year: 2022
Type: article
Abstract: MOTIVATION: CpG sites within the same genomic region often share similar methylation patterns and tend to be co-regulated by multiple genetic variants that may interact with one another. RESULTS: We propose a multi-trait methylation random field (multi-MRF) method to evaluate the joint association between a set of CpG sites and a set of genetic variants. The proposed method has several advantages. First, it is a multi-trait method that allows flexible correlation structures between neighboring CpG sites (e.g. distance-based correlation). Second, it is also a multi-locus method that integrates the effect of multiple common and rare genetic variants. Third, it models the methylation traits with a beta distribution to characterize their bimodal and interval properties. Through simulations, we demonstrated that the proposed method had improved power over some existing methods under various disease scenarios. We further illustrated the proposed method via an application to a study of congenital heart defects (CHDs) with 83 cardiac tissue samples. Our results suggested that gene BACE2, a methylation quantitative trait locus (QTL) candidate, colocalized with expression QTLs in artery tibial and harbored genetic variants with nominal significant associations in two genome-wide association studies of CHD. AVAILABILITY AND IMPLEMENTATION: https://github.com/chenlyu2656/Multi-MRF. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
DOI: 10.1093/bioinformatics/btac443
Authors: Chen Lyu, Manyan Huang, Nianjun Liu, Zhongxue Chen, Philip J Lupo, Benjamin Tycko, John S Witte, Charlotte A Hobbs, Ming Li
Institutions: Indiana University Bloomington, New York University, Indiana University, Baylor College of Medicine, Stanford University, Rady Children's Institute for Genomic Medicine
Language: English
Open Access status: bronze
Awards: Random Field Modelling of Genetic and Epigenetic Association for Congenital Heart Defects in the Presence of Disease Heterogeneity, Genomic/Epigenomic Factors and Non-Syndromic Congenital Heart Defect Risk , Secondary analysis and risk prediction of dental caries and oral clefts, A telescopic algorithm for two-dimensional hidden Markov models with application to genetic studies, High-dimensional statistical genetic methods for dental caries and orofacial clefts, Gene-by-Gene and Gene-by-Environment Interactions Underlying Congenital Heart Defects
OpenAlex ID: W4283793712
FWCI:
Cites: 45
Cited by:
Related to: 10