Association study in eating disorders: TPH2 associates with anorexia nervosa and self‐induced vomiting |
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| Authors: | 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 de Zwaan S Herpertz S 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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| Institution: | 1. Center for Eating Disorders Ursula, Leidschendam;2. Department of Medical Statistics, Molecular Epidemiology Section, Leiden University Medical Centre, Leiden;3. Department of Biological Psychology, VU University, Amsterdam;4. De Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam;5. Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden;6. Department of Psychiatry and Psychology, St Antonius Hospital, Utrecht;7. Emergis, Department of Eating Disorders, Goes;8. Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht;9. Altrecht Mental Health Institute, Rintveld Centre for Eating Disorders, Zeist, The Netherlands;10. Department of Psychosomatic Medicine and Psychotherapy, University Medical Hospital, Tübingen;11. Department of Psychosomatic and General Internal Medicine, University Medical Hospital, Heidelberg;12. Department of Child and Adolescent Psychiatry and Psychotherapy, Universit?tsklinikum Aachen, Aachen;13. Department of Child and Adolescent Psychiatry and Psychotherapy, Julius‐Maximilians University of Würzburg, Würzburg;14. Clinic and Day Clinic of Child and Adolescent Psychiatry and Psychotherapy, Albert Ludwigs‐University of Freiburg, Freiburg i. Br.;15. Department of Psychosomatic Medicine and Psychotherapy, University of Freiburg, Freiburg;16. Department for Psychosomatic Medicine and Psychotherapy, University Erlangen‐Nuremberg, Erlangen;17. Clinic of Psychosomatic Medicine and Psychotherapy, LWL‐University Clinic, Ruhr‐University Bochum;18. Department of Child and Adolescent Psychiatry, Charité–Universit?tsmedizin Berlin, Berlin, Germany;19. Translational Developmental Neuroscience Section, Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany;20. Department of Child and Adolescent Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands;21. Department of Child and Adolescent Psychiatry and Psychotherapy, LVR Klinkum Essen, University of Duisburg‐Essen, Essen, Germany |
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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. |
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| Keywords: | Anorexia nervosa candidate genes genetic association study TPH2 self‐induced vomiting |
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