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Landt, M.C.T.S.O. 't; Meulenbelt, I.; Bartels, M.; Suchiman, E.; Middeldorp, C.M.; Houwing-Duistermaat, J.J.; ... ; Slagboom, P.E. (2010)

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

Article / Letter to editor
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...Show moreTwin 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.Show less
All authors
Landt, M.C.T.S.O. 't; Meulenbelt, I.; Bartels, M.; Suchiman, E.; Middeldorp, C.M.; Houwing-Duistermaat, J.J.; Trier, J. van; Onkenhout, E.J.; Vink, J.M.; Beijsterveldt, C.E.M. van; Brandys, M.K.; Sanders, N.; Zipfel, S.; Herzog, W.; Herpertz-Dahlmann, B.; Klampfl, K.; Fleischhaker, C.; Zeeck, A.; Zwaan, M. de; Herpertz, S.; Ehrlich, S.; Elburg, A.A. van; Adan, R.A.H.; Scherag, S.; Hinney, A.; Hebebrand, J.; Boomsma, D.I.; Furth, E.F. van; Slagboom, P.E.
Date
2010-10-14
Journal
Genes, Brain and Behavior
DOI
doi:10.1111/j.1601-183X.2010.00660.x