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High-throughput DNA methylation analysis in anorexia nervosa confirms TNXB hypermethylation |
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| Authors: | Miriam Kesselmeier Carolin Pütter Anna-Lena Volckmar Hansjörg Baurecht Harald Grallert Thomas Illig |
| Affiliation: | 1. Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany;2. Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany;3. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;4. Department of Dermatology, Allergology, and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;5. Research Unit of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;6. German Center for Diabetes Research, Neuherberg, Germany;7. Hannover Unified Biobank, Hannover Medical School, Hannover, Germany;8. Institute of Human Genetics, Hannover Medical School, Hannover, Germany |
| Abstract: | Objectives: Patients with anorexia nervosa (AN) are ideally suited to identify differentially methylated genes in response to starvation. Methods: We examined high-throughput DNA methylation derived from whole blood of 47 females with AN, 47 lean females without AN and 100 population-based females to compare AN with both controls. To account for different cell type compositions, we applied two reference-free methods (FastLMM-EWASher, RefFreeEWAS) and searched for consensus CpG sites identified by both methods. We used a validation sample of five monozygotic AN-discordant twin pairs. Results: Fifty-one consensus sites were identified in AN vs. lean and 81 in AN vs. population-based comparisons. These sites have not been reported in AN methylation analyses, but for the latter comparison 54/81 sites showed directionally consistent differential methylation effects in the AN-discordant twins. For a single nucleotide polymorphism rs923768 in CSGALNACT1 a nearby site was nominally associated with AN. At the gene level, we confirmed hypermethylated sites at TNXB. We found support for a locus at NR1H3 in the AN vs. lean control comparison, but the methylation direction was opposite to the one previously reported. Conclusions: We confirm genes like TNXB previously described to comprise differentially methylated sites, and highlight further sites that might be specifically involved in AN starvation processes. |
| Keywords: | Anorexia nervosa DNA methylation eating disorder epigenome-wide association study starvation |