Clinical features of psychotic disorders and polymorphisms in HT2A, DRD2, DRD4, SLC6A3 (DAT1), and BDNF: a family based association study

Ayman H Fanous, M C Neale, R E Straub, B T Webb, Francis O'Neill, D Walsh, K S Kendler

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

Schizophrenia is clinically heterogeneous and multidimensional, but it is not known whether this is due to etiological heterogeneity. Previous studies have not consistently reported association between any specific polymorphisms and clinical features of schizophrenia, and have primarily used case-control designs. We tested for the presence of association between clinical features and polymorphisms in the genes for the serotonin 2A receptor (HT2A), dopamine receptor types 2 and 4, dopamine transporter (SLC6A3), and brain-derived neurotrophic factor (BDNF). Two hundred seventy pedigrees were ascertained on the basis of having two or more members with schizophrenia or poor outcome schizoaffective disorder. Diagnoses were made using a structured interview based on the SCID. All patients were rated on the major symptoms of schizophrenia scale (MSSS), integrating clinical and course features throughout the course of illness. Factor analysis revealed positive, negative, and affective symptom factors. The program QTDT was used to implement a family-based test of association for quantitative traits, controlling for age and sex. We found suggestive evidence of association between the His452Tyr polymorphism in HT2A and affective symptoms (P = 0.02), the 172-bp allele of BDNF and negative symptoms (P = 0.04), and the 480-bp allele in SLC6A3 (= DAT1) and negative symptoms (P = 0.04). As total of 19 alleles were tested, we cannot rule out false positives. However, given prior evidence of involvement of the proteins encoded by these genes in psychopathology, our results suggest that more attention should be focused on the impact of these alleles on clinical features of schizophrenia.
Original languageEnglish
Pages (from-to)69-78
Number of pages10
JournalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Volume125B
Issue number1
DOIs
Publication statusPublished - 15 Feb 2004

Bibliographical note

Copyright 2003 Wiley-Liss, Inc.

Keywords

  • Alleles
  • Brain-Derived Neurotrophic Factor
  • Dopamine Plasma Membrane Transport Proteins
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Polymorphism, Genetic
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • Schizophrenia
  • Schizophrenic Psychology
  • Transcription Factors

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