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Pilot study on HTR2A promoter polymorphism, −1438G/A (rs6311) and a nearby copy number variation showed association with onset and severity in early onset obsessive–compulsive disorder

  • Biological Child and Adolescent Psychiatry - Original Article
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Abstract

A previous study showed that a single nucleotide polymorphism (SNP), −1438G/A (rs6311), found in the transcriptional control region of the gene that encodes the serotonin-receptor 2A (HTR2A) was associated with obsessive–compulsive disorder (OCD) in a sample of children and adolescents. In this study, we reanalyzed the association of this SNP with OCD in an enlarged population of 136 cases (55 previous + 81 new cases) and compared them to 106 newly recruited, healthy, age-matched controls. We also investigated whether this SNP or its copy number variations (CNV) was associated with OCD severity and age of onset. The CNV was analyzed in a DNA region located near rs6311. The results confirmed the association between the A-allele and early onset OCD in children and adolescents, with an odds ratio (OR) of 1.69 [95% CI (1.17, 2.46); p = 0.005]. Strikingly, we found that carriers of one copy (deletion) of the CNV were associated with a very early onset OCD (2.5 years earlier than the typical onset), and they had increased CY-BOCS scores (8.7 points higher compared to “normal” CNV and duplications); which is related to increased severity of OCD symptoms (p = 0.031; p = 0.004, respectively). Compared to the normal CNV and duplications, the association between the deletion and OCD showed an OR of 7.56 [95% CI (1.32, 142.84); p = 0.020]. These results pointed to the functional importance of this promoter region of HTR2A; it influenced the occurrence, the onset, and the severity of OCD.

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Acknowledgments

We would like to express our gratitude to all participants. In addition, we would also like to thank M. Hofmann, T. Elpel, and G. Ortega for their excellent technical assistance. The study was supported by the Deutsche Forschungsgemeinschaft WA 1618 and the KFO 125.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Hospital of Child and Adolescent Psychiatry, University of Zurich, Neumuensterallee 9, 8032, Zurich, Switzerland

    Susanne Walitza & Edna Grünblatt

  2. Clinical Neurochemistry Laboratory, Clinic and Policlinic for Psychiatry, Psychosomatic and Psychotherapy, University of Wuerzburg, 97080, Wuerzburg, Germany

    Edna Grünblatt

  3. Division of Biostatistics, Institute for Social and Preventive Medicine, University of Zurich, Hirschengraben 84, 8001, Zurich, Switzerland

    Daniel Sabanés Bové & Leonhard Held

  4. Department of Child and Adolescent Psychiatry, University of Wuerzburg, 97080, Wuerzburg, Germany

    Marcel Romanos, Tobias Renner & Andreas Warnke

  5. Department of Child and Adolescent Psychiatry, University of Munich, 80336, Munich, Germany

    Marcel Romanos

  6. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, Neuenhofer Weg 21, 52074, Aachen, Germany

    Michael Simons

  7. Municipal Hospitals of Cologne, Clinic for Child and Adolescent Psychiatry and Psychotherapy, Florentine-Eichler-Str. 1, 51067, Köln, Germany

    Christoph Wewetzer

  8. Department of Child and Adolescent Psychiatry, University Freiburg, 79104, Freiburg, Germany

    Christian Fleischhaker

  9. Department of Child and Adolescent Psychiatry, Philipps-University Marburg, 35039, Marburg, Germany

    Helmut Remschmidt

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  1. Susanne Walitza
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  11. Edna Grünblatt
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Correspondence to Susanne Walitza.

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Walitza, S., Bové, D.S., Romanos, M. et al. Pilot study on HTR2A promoter polymorphism, −1438G/A (rs6311) and a nearby copy number variation showed association with onset and severity in early onset obsessive–compulsive disorder. J Neural Transm 119, 507–515 (2012). https://doi.org/10.1007/s00702-011-0699-1

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