Association Study among Comethylation Modules, Genetic Polymorphisms and Clinical Features in Mexican Teenagers with Eating Disorders: Preliminary Results.

Germán Alberto Nolasco-Rosales,David Ruiz-Ramos,Ana Rosa García,Humberto Nicolini,Isela Esther Juárez-Rojop,José Jaime Martínez-Magaña,Emmanuel Sarmiento,Alma Delia Genis-Mendoza,Thelma Beatriz González-Castro,Carlos Alfonso Tovilla-Zarate

doi:10.3390/nu13093210

Abstract

Eating disorders are psychiatric disorders characterized by disturbed eating behaviors. They have a complex etiology in which genetic and environmental factors interact. Analyzing gene-environment interactions could help us to identify the mechanisms involved in the etiology of such conditions. For example, comethylation module analysis could detect the small effects of epigenetic interactions, reflecting the influence of environmental factors. We used MethylationEPIC and Psycharray microarrays to determine DNA methylation levels and genotype from 63 teenagers with eating disorders. We identified 11 comethylation modules in WGCNA (Weighted Gene Correlation Network Analysis) and correlated them with single nucleotide polymorphisms (SNP) and clinical features in our subjects. Two comethylation modules correlated with clinical features (BMI and height) in our sample and with SNPs associated with these phenotypes. One of these comethylation modules (yellow) correlated with BMI and rs10494217 polymorphism (associated with waist-hip ratio). Another module (black) was correlated with height, rs9349206, rs11761528, and rs17726787 SNPs; these polymorphisms were associated with height in previous GWAS. Our data suggest that genetic variations could alter epigenetics, and that these perturbations could be reflected as variations in clinical features.

Highlights

Concerning psychiatric disorders, we found several single nucleotide polymorphisms (SNP) to be associated with three comethylation modules
Little information is available about the integration of these different levels disturb adipose tissue function and alter Body Mass Index (BMI) in individuals diagnosed with an Eating disorders (EDs)
Schizophrenia was not correlated in our sample, we found genes and SNPs associated with the disorder

Summary

Introduction

The clinical characteristics of EDs have been associated in genetic studies. Analyzing gene-environment interactions in EDs could help us to identify the mechanisms involved in their etiology. Comethylation modules are clusters of highly interconnected CpG sites These modules are detected through the construction of a correlation network. Correlation networks are used to analyze large, high-dimensional data sets These correlation networks are constructed on the basis of correlations among quantitative measurements (e.g., gene expression profiles, methylation levels) [11]. Comethylation modules are formed by using methylation data as quantitative measurements of gene-environment interactions [10]. Comethylation modules alleviate various testing problems which are inherent to microarray data analyses, and have been found to be useful for describing pairwise relationships among methylated genes [9,10,11]. Comethylation modules (1) consider all genes as interconnected,

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