The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · 2016
High-throughput DNA methylation analysis in anorexia nervosa confirms TNXB hypermethylation.
СтатьяПоддержка исследования: вне правительства СШАTwin StudyНазвание и аннотация: Перевод пока не подготовлен
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Kesselmeier Miriam, Pütter Carolin, Volckmar Anna-Lena, Baurecht Hansjörg, Grallert Harald, Illig Thomas, Ismail Khadeeja, Ollikainen Miina, Silén Yasmina, Keski-Rahkonen Anna, Bulik Cynthia M, Collier David A, Zeggini Eleftheria, Hebebrand Johannes, Scherag André, Hinney Anke, GCAN and WTCCC3
Аннотация
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.
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.