Association study in eating disorders: TPH2 associates with anorexia nervosa and self induced vomiting

M.C.T. Slof-Op 't Landt, I. Meulenbelt, M. Bartels, E. Suchiman, C.M. Middeldorp, J.J. Houwing-Duistermaat, J. van Trier, E.J. Onkenhout, J.M. Vink, C.E.M. van Beijsterveldt, M.K. Brandys, N. Sanders, S. Zipfel, W. Herzog, B. Herpertz-Dahlmann, K. Klampfl, C. Fleischhaker, A. Zeeck, M. Zwaan, S. HerpertzS. Ehrlich, A.A. van Elburg, R.A.H. Adan, S. Scherag, A. Hinney, J. Hebebrand, D.I. Boomsma, E.F. van Furth, P.E. Slagboom

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Abstract

Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
Original languageEnglish
Pages (from-to)236-243
JournalGenes, Brain and Behavior
Volume10
Issue number2
DOIs
Publication statusPublished - 2011

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