title: Lack of association of genetic variants in genes of the endocannabinoid system with anorexia nervosa.
abstract: BACKGROUND
  Several lines of evidence indicate that the central cannabinoid receptor 1 (CNR1) as well as the major endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA) and monoglyceride lipase (MGLL) are implicated in mediating the orexigenic effects of cannabinoids. The aim of this study was to analyse whether nucleotide sequence variations in the CNR1, FAAH, NAAA and MGLL genes are associated with anorexia nervosa (AN).
  
  
  METHODS
  We analysed the association of a previously described (AAT)n repeat in the 3' flanking region of CNR1 as well as a total of 15 single nucleotide polymorphisms (SNPs) representative of regions with restricted haplotype diversity in CNR1, FAAH, NAAA or MGLL in up to 91 German AN trios (patient with AN and both biological parents) using the transmission-disequilibrium-test (TDT). One SNP was additionally analysed in an independent case-control study comprising 113 patients with AN and 178 normal weight controls. Genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, ARMS-PCR or using 3730xl capillary sequencers.
  
  
  RESULTS
  The TDT revealed no evidence for association for any of the SNPs or the (AAT)n repeat with AN (all two-sided uncorrected p-values > 0.05). The lowest p-value of 0.11 was detected for the A-allele of the CNR1 SNP rs1049353 for which the transmission rate was 59% (95% confidence interval 47%...70%). Further genotyping of rs1049353 in 113 additional independent patients with AN and 178 normal weight controls could not substantiate the initial trend for association (p = 1.00).
  
  
  CONCLUSIONS
  As we found no evidence for an association of genetic variation in CNR1, FAAH, NAAA and MGLL with AN, we conclude that genetic variations in these genes do not play a major role in the etiology of AN in our study groups.
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany.|Department of Psychiatry, University of Cincinnati Genome Research Institute, Cincinnati, OH, USA.
authors.forename: Timo Dirk
authors.initials: TD
authors.lastname: Müller
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany.|Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Reichwald
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany.|Biocenter of the University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Brönner
authors.affiliation: Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Kirschner
authors.affiliation: Institute of Medical Biometry and Epidemiology, Philipps-University, Marburg, Germany.
authors.forename: Thuy Trang
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Institute of Medical Biometry and Epidemiology, Philipps-University, Marburg, Germany.|Institute of Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.affiliation: Klinik für Psychosomatische und Allgemeine Klinische Medizin, Universitätsklinikum Heidelberg, University of Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herzog
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, University Clinics, Technical University of Aachen, Aachen, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Herpertz-Dahlmann
authors.affiliation: Institute of Human Genetics, Technical University Munich, Munich, Germany.|GSF - National Research Center for Environment and Health, München-Neuherberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.affiliation: Institute of Human Genetics, Technical University Munich, Munich, Germany.|GSF - National Research Center for Environment and Health, München-Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.affiliation: Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.affiliation: Institute of Medical Biometry and Epidemiology, Philipps-University, Marburg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Schäfer
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney