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Kesselmeier, M.* ; Pütter, C.* ; Volckmar, A.L.* ; Baurecht, H.* ; Grallert, H. ; Illig, T. ; Ismail, K.* ; Ollikainen, M.* ; Silén, Y.* ; Keski-Rahkonen, A.* ; Bulik, C.M.* ; Collier, D.A.* ; Zeggini, E.* ; Hebebrand, J.* ; Scherag, A.* ; Hinney, A.*

High-throughput DNA methylation analysis in anorexia nervosa confirms TNXB hypermethylation.

World J. Biol. Psychiatry 19, 187-199 (2018)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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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.

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