Despite considerable study, chronic fatigue syndrome (CFS) continues to be both idiopathic and controversial. CFS is associated with considerable morbidity, impairment, and chronicity. Multiple lines of investigation have not yielded widely-accepted and empirically-based hypotheses about its etiology. The goal of this application is to identify biomarkers for CFS, which can also be used to generate hypotheses about the etiology of CFS. The current plan is to correlate microarray and proteomic techniques to biological samples from monozygotic twins who are rigorously discordant for CFS. Discordant monozygotic twins represent an excellent case-control design given their high degree of genetic matching and similarity for many environmental variables and exposure. 28.089 twins from the population-based Swedish Twin Registry have already screened for the symptoms of CFS (funded by NS-41483) and 156 pairs of monozygotic twins, preliminarily discordant for CFS-like illness, have been documented. The application requests funds for clinical evaluation in order to recruit and classify 50 monozygotic twin pairs as rigorously discordant for CFS Zygosity will be proven by genotyping 30 microsatellite markers. Under standardized conditions with careful sample handling, three biological samples can be obtained from consenting twins: total RNA extracted from peripheral blood lymphocytes, peripheral serum, and cerebrospinal fluid. The RNA sample will be analyzed with Affymetrix HG-U133 microarrays that interrogate approximately 45,000 mRNA targets from approximately 33,000 validated human genes. Following removal of high abundance proteins, serum and cerebrospinal fluid samples will be subjected to two-dimensional gel electrophoresis and identification of protein spots of interest via MALDI (aka """"""""proteomics"""""""").False discovery rate calculations to show that this design is capable of identifying biomarkers for CFS under many plausible scenarios. Sophisticated statistical, data mining, and bioinformatic techniques will be applied to these data to understand the high dimensionality data generated in these experiments. The team of investigators and consultants assembled for this project has the proven capacity to perform all aspects of this project. This project has the potential to identify biomarkers for CFS and to derive falsifiable hypotheses about its etiology. If successful, this work could lead to profound changes in the understanding of CFS and resolution of some attendant controversies.
| Thornton, Laura M; Welch, Elisabeth; Munn-Chernoff, Melissa A et al. (2016) Anorexia Nervosa, Major Depression, and Suicide Attempts: Shared Genetic Factors. Suicide Life Threat Behav 46:525-534 |
| Peterson, Claire M; Baker, Jessica H; Thornton, Laura M et al. (2016) Genetic and environmental components to self-induced vomiting. Int J Eat Disord 49:421-7 |
| Algars, Monica; Huang, Lu; Von Holle, Ann F et al. (2014) Binge eating and menstrual dysfunction. J Psychosom Res 76:19-22 |
| Trace, Sara E; Thornton, Laura M; Baker, Jessica H et al. (2013) A behavioral-genetic investigation of bulimia nervosa and its relationship with alcohol use disorder. Psychiatry Res 208:232-7 |
| Pisetsky, Emily M; Thornton, Laura M; Lichtenstein, Paul et al. (2013) Suicide attempts in women with eating disorders. J Abnorm Psychol 122:1042-56 |
| Trace, Sara E; Thornton, Laura M; Root, Tammy L et al. (2012) Effects of reducing the frequency and duration criteria for binge eating on lifetime prevalence of bulimia nervosa and binge eating disorder: implications for DSM-5. Int J Eat Disord 45:531-6 |
| Trace, Sara E; Thornton, Laura M; Runfola, Cristin D et al. (2012) Sleep problems are associated with binge eating in women. Int J Eat Disord 45:695-703 |
| Sullivan, Patrick F; Allander, Tobias; Lysholm, Fredrik et al. (2011) An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue. BMC Microbiol 11:2 |
| Thornton, Laura M; Dellava, Jocilyn E; Root, Tammy L et al. (2011) Anorexia nervosa and generalized anxiety disorder: further explorations of the relation between anxiety and body mass index. J Anxiety Disord 25:727-30 |
| Kato, Kenji; Sullivan, Patrick F; Pedersen, Nancy L (2010) Latent class analysis of functional somatic symptoms in a population-based sample of twins. J Psychosom Res 68:447-53 |
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