title: High-throughput DNA methylation analysis in anorexia nervosa confirms TNXB hypermethylation.
abstract: Patients with anorexia nervosa (AN) are ideally suited to identify differentially methylated genes in response to starvation.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: a Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital , Jena , Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Kesselmeier
authors.affiliation: b Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen , Essen , Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Pütter
authors.affiliation: c Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy , University Hospital Essen, University of Duisburg-Essen , Essen , Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Volckmar
authors.affiliation: d Department of Dermatology, Allergology, and Venereology , University Hospital Schleswig-Holstein , Campus Kiel, Kiel , Germany.
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Baurecht
authors.affiliation: e Research Unit of Molecular Epidemiology , Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health , Neuherberg , Germany.|f German Center for Diabetes Research , Neuherberg , Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.affiliation: e Research Unit of Molecular Epidemiology , Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health , Neuherberg , Germany.|g Hannover Unified Biobank , Hannover Medical School , Hannover , Germany.|h Institute of Human Genetics , Hannover Medical School , Hannover , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: i Department of Public Health , University of Helsinki , Helsinki , Finland.
authors.forename: Khadeeja
authors.initials: K
authors.lastname: Ismail
authors.affiliation: i Department of Public Health , University of Helsinki , Helsinki , Finland.
authors.forename: Miina
authors.initials: M
authors.lastname: Ollikainen
authors.affiliation: i Department of Public Health , University of Helsinki , Helsinki , Finland.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Silén
authors.affiliation: i Department of Public Health , University of Helsinki , Helsinki , Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Keski-Rahkonen
authors.affiliation: j Department of Psychiatry , University of North Carolina at Chapel Hill , Chapel Hill , NC , USA.|k Department of Nutrition , The University of North Carolina at Chapel Hill , Chapel Hill , NC , USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Bulik
authors.affiliation: l Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London , London , UK.|m Eli Lilly and Company, Erl Wood Manor , Windlesham , UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.affiliation: n Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus , Hinxton , Cambridge , UK.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.affiliation: c Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy , University Hospital Essen, University of Duisburg-Essen , Essen , Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
authors.affiliation: a Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital , Jena , Germany.
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.affiliation: c Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy , University Hospital Essen, University of Duisburg-Essen , Essen , Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
mesh_terms: D000328:Adult; D000856:Anorexia Nervosa / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017422:Sequence Analysis, DNA; D013217:Starvation / Q000235:genetics*; D019063:Tenascin / Q000235:genetics*; D013851:Thinness / Q000235:genetics*; D055815:Young Adult
chemical_list: D019063:Tenascin; C081865:tenascin X
keywords: Anorexia nervosa; DNA methylation; eating disorder; epigenome-wide association study; starvation