期刊
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
卷 19, 期 3, 页码 187-199出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/15622975.2016.1190033
关键词
Anorexia nervosa; DNA methylation; eating disorder; epigenome-wide association study; starvation
类别
资金
- Agenome-wide association study of anorexia nervosa [GCAN/WTCCC3 WT088827/Z/09]
- Wellcome Trust [WT098051]
- Deutsche Forschungsgemeinschaft'' (DFG) [HI865/2-1]
- BMBF [01GS0820]
- Landesmittel NRW, Landesprogramm Geschlechtergerechte Hochschulen, Academy of Finland [265240]
- EPITRAIN - FP7-PEOPLE-ITN [316758]
- Federal Ministry of Education and Research (BMBF), Germany [FKZs 01EO1002, 01EO1502]
- Academy of Finland [251316]
- Sigrid Juselius Foundation
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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