Methods for detecting methylation by SNP interaction in GAW20 simulation

E Warwick Daw,Michael A Province,Petra Lenzini,Ping An,Judy Wang,Shiow J Lin,Aldi T Kraja,Christine Williams,James Hicks

doi:10.1186/s12919-018-0140-y

Abstract

To examine whether single-nucleotide polymorphism (SNP) by methylation interactions can be detected, we analyzed GAW20 simulated triglycerides at visits 3 and 4 against baseline (visits 1 and 2) under 4 general linear models and 2 tree-based models in 200 replications of a sample of 680 individuals. Effects for SNPs, methylation cytosine-phosphate-guanine (CpG) effects, and interactions for SNP/CpG pairs were included. Causative SNPs/CpG pairs distributed on autosomal chromosomes 1 to 20 were tested to examine sensitivity. We also tested noncausative SNP/CpG pairs on chromosomes 21 and 22 to estimate the empirical null. We found reasonable power to detect the main causative loci, with the exact power depending on sample size and strength of effects at the SNP and CpG sites.

Highlights

DNA methylation is an important epigenetic mark at transcriptional start sites, regulatory elements, repeat sequences, or within a gene [1]
We examined Type I error and power for identifying single-nucleotide polymorphisms (SNPs) by methylation interactions under several methods with different models
We identified 2267 SNPs with nearby methylation markers on chromosomes 21 and 22, which we used to generate empirical null distributions for identifying SNP by methylation interactions

Summary

Introduction

Introduction DNA methylation is an important epigenetic mark at transcriptional start sites, regulatory elements, repeat sequences, or within a gene [1]. We examined Type I error and power for identifying single-nucleotide polymorphisms (SNPs) by methylation interactions under several methods with different models. Our goal was to examine the feasibility of detecting gene by methylation interactions. Null SNP interactions 380,800 (w/MAC > 50). To obtain an empirical null distribution for Methods I and II, we identified 2267 SNP–CpG pairs on chromosomes 21 and 22, where there were no simulated causative SNPs. A pair of markers was identified by selecting a SNP, and a CpG that is adjacent but has a higher base-pair position than the SNP. For chromosome 22, we formed 1450 pairs from 9464 SNPs and 8381 CpG sites

Objectives

Methods

Results

Conclusion