Fibromyalgia (FM), characterized by chronic widespread pain, fatigue, and cognitive/mood disturbances, leads to reduced workplace productivity and increased healthcare expenses. To determine if acquired epigenetic/genetic changes are associated with FM, we compared the frequency of spontaneously occurring micronuclei (MN) and genome-wide methylation patterns in women with FM ( ) to those seen in comparably aged healthy controls ( (MN); (methylation)). The mean (sd) MN frequency of women with FM (51.4 (21.9)) was significantly higher than that of controls (15.8 (8.5)) ( ; df = 1; ). Significant differences ( sites) in methylation patterns were observed between cases and controls considering a 5% false discovery rate. The majority of differentially methylated (DM) sites (91%) were attributable to increased values in the women with FM. The DM sites included significant biological clusters involved in neuron differentiation/nervous system development, skeletal/organ system development, and chromatin compaction. Genes associated with DM sites whose function has particular relevance to FM included BDNF, NAT15, HDAC4, PRKCA, RTN1, and PRKG1. Results support the need for future research to further examine the potential role of epigenetic and acquired chromosomal alterations as a possible biological mechanism underlying FM. 1. Introduction Fibromyalgia (FM), which affects at least 10 million American adults [1], is a multisymptom condition resulting in not only widespread chronic pain, but also fatigue, sleep disturbances, and morning stiffness. In addition, many patients experience depression, anxiety, and dyscognition [2, 3]. FM has a significant adverse impact on many individuals’ physical and mental health [4, 5] and also leads to reduced workplace productivity and increased health care/disability expenses, with the estimated cost of FM on the US economy being reported to be 12–14 billion dollars [1, 6]. While the adverse impact of this condition is indisputable, its etiology remains enigmatic. Due to the lack of clarity for the underlying cause(s) of FM, it poses a diagnostic challenge, often requiring multiple visits by specialists to render a diagnosis [7]. The lack of understanding of the biological basis of this condition also confounds our ability to develop effective interventions and/or monitor disease progression. FM has been suggested to be a complex, multifactorial trait that is influenced by age, gender (frequency is the highest in middle-aged females), and stress/trauma. Despite showing a strong familial aggregation [8–10], attempts to identify
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