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Anorexia nervosa and the Val158Met polymorphism of the COMT gene: meta-analysis and new data

Brandys, Marek K.a,d; Slof-Op’t Landt, Margarita C.T.e,f,i; van Elburg, Annemarie A.c,d; Ophoff, Roelb,l; Verduijn, Willemg; Meulenbelt, Ingridf; Middeldorp, Christel M.i,j,k; Boomsma, Dorret I.i; van Furth, Eric F.e; Slagboom, Elinef,h; Kas, Martien J. H.a; Adan, Roger A.H.a,d

doi: 10.1097/YPG.0b013e328351859e
Original Articles

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.

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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:

Received May 25, 2011

Accepted October 3, 2011

© 2012 Lippincott Williams & Wilkins, Inc.