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The 5-HT2A −1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres

Molecular Psychiatry volume 7, pages 90–94 (2002)Cite this article

Abstract

Several case-control association studies have raised the possibility that the A allele of a −1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A) gene may be a risk factor for anorexia nervosa. However the absence of linkage and the existence of negative association studies raise the possibility of false positive findings, resulting from population stratification or lack of statistical power. To address this controversy we recruited a sample of 316 patients with anorexia nervosa from six European centres, and utilised a family-based transmission disequilibrium (TDT) approach to analyse the HTR2A-1438 G/A polymorphism. Age at onset and minimal BMI were also taken into consideration in order to detect clinical heterogeneity or a quantitative trait effect. The TDT approach showed that the A allele was transmitted 133 times and not transmitted 148 times (McNemar χ2 = 0.29, df = 1, P = 0.59). Also, the haplotype-based haplotype relative risk method showed no evidence for association of the A allele, in samples from each centre (χ2 < 2.15, df = 1, P > 0.14) and in the total sample (χ2 = 0.55, df = 1; P = 0.46). Furthermore, we found no evidence for heterogeneity of the A allele frequency between samples (χ2 = 2.54, df = 4, P = 0.64), either according to minimal-BMI (F1/242 = 2.14, P = 0.45) or age at onset (F1/224 = 2.39; P = 0.12). QTL-TDT analyses also showed no direct role of the A allele on these traits. We thus found no evidence for a significant role of the 5-HT2A gene in anorexia nervosa. Previous results may have been exposed to stratification bias (which we controlled by the TDT method) and/or the risk of type 1 error (from which we were less exposed because of the sample size).

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Author notes

  1. P Gorwood, J Adès, L Bellodi, E Cellini, D A Collier, D Di Bella, M Di Bernardo, X Estivill, F Fernandez-Aranda, M Gratacos, J Hebebrand, A Hinney, X Hu, A Karwautz, A Kipman, M-C Mouren-Siméoni, B Nacmias, M Ribasés, H Remschmidt, V Ricca, C M Rotella, S Sorbi and J Treasure: Co-ordinated by Janet Treasure and David Collier.

Authors and Affiliations

  1. CHU Louis Mourier, Assistance-Publique des Hôpitaux de Paris cedex, 178, rue des Renouillers, Colombes, 92701, France

    P Gorwood, J Adès, A Kipman & M-C Mouren-Siméoni

  2. Department of Neuropsychiatric Sciences (DSNP), Fondazione Centro S Raffaele del Monte Tabor, Via Prinetti 29, Milan, 21127, Italy

    L Bellodi & D Di Bella

  3. Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, Florence, 50134, Italy

    E Cellini, M Di Bernardo, B Nacmias, V Ricca, C M Rotella & S Sorbi

  4. Eating Disorders Unit, and Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK

    D A Collier, X Hu, A Karwautz & J Treasure

  5. Centre de Genètica Mèdica i Molecular (CGMM-IRO), Hospital Duran y Reynals, Ctra de Castelldefels Km, 2, 7, L'hospitalet de Llobregat, Barcelona, 08907, Spain

    X Estivill, M Gratacos & M Ribasés

  6. Department of Psychiatry, Hospital Principes D'Espana, Feixa Llarga S/N, 08907 L'hospitalet de Llobregat, Barcelona, Spain

    F Fernandez-Aranda

  7. Department of Child and Adolescent Psychiatry, Clinical Research Group, Philipps University Marburg, Schuetzenstrasse 49, Marburg, 35033, Germany

    J Hebebrand, A Hinney & H Remschmidt

  8. University Clinic of Neuropsychiatry of Childhood and Adolescence, Waehringer Guertel 18–20 Post Code, Vienna, A-1090, Austria

    A Karwautz

Authors
  1. P Gorwood
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  2. J Adès
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  3. L Bellodi
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  4. E Cellini
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  5. D A Collier
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  6. D Di Bella
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  7. M Di Bernardo
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  8. X Estivill
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  9. F Fernandez-Aranda
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  10. M Gratacos
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  11. J Hebebrand
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  12. A Hinney
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  13. X Hu
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  14. A Karwautz
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  15. A Kipman
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  16. M-C Mouren-Siméoni
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  17. B Nacmias
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  18. M Ribasés
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  19. H Remschmidt
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  20. V Ricca
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  21. C M Rotella
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  22. S Sorbi
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  23. J Treasure
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(EC Framework V ‘Factors in Healthy Eating’ consortium)

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Correspondence to P Gorwood.

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Gorwood, P., Adès, J., Bellodi, L. et al. The 5-HT2A −1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres. Mol Psychiatry 7, 90–94 (2002). https://doi.org/10.1038/sj.mp.4000938

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