Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome.

K A Schlauch,S F Khaiboullina,D Kulick,J Petereit,N Blatt,S Rawat,A A Rizvanov,T Mijatovic,A Palotás,K L De Meirleir,V C Lombardi

doi:10.1038/tp.2015.208

K A Schlauch, S F Khaiboullina + Show 9 more

Open Access

https://doi.org/10.1038/tp.2015.208

Copy DOI

Abstract

Myalgic encephalomyelitis, also known as chronic fatigue syndrome or ME/CFS, is a multifactorial and debilitating disease that has an impact on over 4 million people in the United States alone. The pathogenesis of ME/CFS remains largely unknown; however, a genetic predisposition has been suggested. In the present study, we used a DNA single-nucleotide polymorphism (SNP) chip representing over 906,600 known SNPs to analyze DNA from ME/CFS subjects and healthy controls. To the best of our knowledge, this study represents the most comprehensive genome-wide association study (GWAS) of an ME/CFS cohort conducted to date. Here 442 SNPs were identified as candidates for association with ME/CFS (adjusted P-value<0.05). Whereas the majority of these SNPs are represented in non-coding regions of the genome, 12 SNPs were identified in the coding region of their respective gene. Among these, two candidate SNPs resulted in missense substitutions, one in a pattern recognition receptor and the other in an uncharacterized coiled-coil domain-containing protein. We also identified five SNPs that cluster in the non-coding regions of T-cell receptor loci. Further examination of these polymorphisms may help identify contributing factors to the pathophysiology of ME/CFS, as well as categorize potential targets for medical intervention strategies.

Highlights

Myalgic encephalomyelitis, known as chronic fatigue syndrome or ME/CFS, is a complex and heterogeneous disease that has a severe impact on the health and quality of life of those afflicted
Using monozygotic twins to control for genetic differences, Sabath et al reported that ME/CFS cases and their respective twins displayed a trend of increased circulating CD62L(+) T cells in several T-cell subsets.[46]
Other studies suggest that polymorphisms observed in subjects with ME/CFS may associate with the sleep abnormalities and the neurological dysfunction associated with this disease

Summary

INTRODUCTION

Known as chronic fatigue syndrome or ME/CFS, is a complex and heterogeneous disease that has a severe impact on the health and quality of life of those afflicted. Studies of monozygotic and dizygotic twins suggest that there is a higher rate of fatigue concordance in monozygotic twins when compared with dizygotic twins.[15,16] The expression of major histocompatibility complex class II antigens HLA-DQA1*01 and HLA-DR4 has been suggested as a potential risk factor in developing ME/CFS.[17,18] single-nucleotide polymorphisms (SNPs) in the tumor necrosis factor-α and interferon-γ genes may implicate genetic factors in the dysregulation of inflammatory cytokine production.[19]. Only SNPs having a MAF of at least 5% in our sample set were considered

MATERIALS AND METHODS

Findings

DISCUSSION