Objectives: This study aimed to test the association between the Val158Met polymorphism (rs4680) of the catechol-O-methyl transferase gene and anorexia nervosa (AN).
Methods: First, an association study on two cohorts (306 cases and 1009 controls from Utrecht, and 174 cases and 466 controls from Leiden/NTR) was performed. Subsequently, the results were integrated into a meta-analysis, together with all the case–control and family-based studies, which were testing the same hypothesis and were available in the literature. Altogether, eight studies (11 datasets) were included in this meta-analysis, with a total of 2021 cases, 2848 controls, and 89 informative (heterozygous) trios.
Results: The present association studies found no association between AN and rs4680 when testing the allelic contrast [Utrecht odds ratio (OR)=1.14, P=0.14; Leiden OR=1.02, P=0.85]. There was an indication of an association under the dominant model of genetic effect in the Utrecht cohort (for the Met allele, OR=1.42, P=0.03). Nevertheless, the meta-analyses of both the allelic contrast and the dominant effect were nonsignificant (the allelic pooled OR=1.03, P=0.42 and the dominant pooled OR=1.1, P=0.18). The meta-analyses were performed under the fixed-effect model and there was no significant heterogeneity among the effect sizes.
Conclusion: Meta-analytically combined evidence from the present genotypings and the literature search shows that the effect sizes are homogeneous across studies and that rs4680 is not associated with AN.
Departments of aNeuroscience and Pharmacology
bPsychiatry, Rudolf Magnus Institute of Neuroscience
cDepartment of Child and Adolescent Psychiatry, University Medical Center, Utrecht
dRintveld Center for Eating Disorders, Altrecht Mental Health Institute, Zeist
eCenter for Eating Disorders Ursula, Leidschendam
fDepartment of Medical Statistics, Molecular Epidemiology Section
gDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center
hThe Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden
iDepartment of Biological Psychology, VU University
jDepartment of Child and Adolescent Psychiatry, Academic Medical Center
kDepartment of Child and Adolescent Psychiatry, GGZ inGeest/VU Medical Center, Amsterdam, The Netherlands
lCenter for Neurobehavioral Genetics, Neuropsychiatric Institute, University of California Los Angeles, Los Angeles, California, USA
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Correspondence to Roger A.H. Adan, PhD, The Rudolf Magnus Institute of Neuroscience, UMC Utrecht, STR 5.203 Heidelberglaan 100, PO Box 85500, 3508GA Utrecht, The Netherlands Tel: +31 887 568 517; fax: +31 887 569 032; e-mail: firstname.lastname@example.org
Received May 25, 2011
Accepted October 3, 2011