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


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.

DOI: 10.1080/15622975.2016.1190033

Cite this paper

@article{Kesselmeier2016HighthroughputDM, title={High-throughput DNA methylation analysis in anorexia nervosa confirms TNXB hypermethylation.}, author={Miriam Kesselmeier and Carolin Puetter and Anna-Lena Volckmar and H. Baurecht and Harald Grallert and Thomas Illig and Khadeeja Ismail and Miina Ollikainen and Yasmina Sil{\'e}n and Anna Keski-Rahkonen and Cynthia M Bulik and David A. Collier and Eleftheria Zeggini and Johannes Hebebrand and Andr{\'e} Scherag and Anke Hinney}, journal={The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry}, year={2016}, pages={1-13} }