Human Genetics

, Volume 124, Issue 6, pp 607–613

A common haplotype of DRD3 affected by recent positive selection is associated with protection from schizophrenia

Authors

    • Fundación Pública Galega de Medicina Xenómica (FPGMX)-SERGASUniversity of Santiago Hospital Complex
  • Noa Carrera
    • Fundación Pública Galega de Medicina Xenómica (FPGMX)-SERGASUniversity of Santiago Hospital Complex
  • Eduardo Domínguez
    • Applied Pharmacology to Membrane Biology and Signal Transduction Mechanisms Research Group (BIOFARMA), Departament de FarmacologyUniversity of Santiago de Compostela
  • Elisabet Vilella
    • Faculty of Medicine, Psychiatric Hospital Institut Pere MataUniversity Rovira i Virgili
  • Lourdes Martorell
    • Faculty of Medicine, Psychiatric Hospital Institut Pere MataUniversity Rovira i Virgili
  • Joaquín Valero
    • Faculty of Medicine, Psychiatric Hospital Institut Pere MataUniversity Rovira i Virgili
  • Alfonso Gutiérrez-Zotes
    • Faculty of Medicine, Psychiatric Hospital Institut Pere MataUniversity Rovira i Virgili
  • Antonio Labad
    • Faculty of Medicine, Psychiatric Hospital Institut Pere MataUniversity Rovira i Virgili
  • Ángel Carracedo
    • Fundación Pública Galega de Medicina Xenómica (FPGMX)-SERGASUniversity of Santiago Hospital Complex
    • Genomic Medicine Group, Institute of Legal Medicine, CEGEN and CIBERERUniversity of Santiago de Compostela
Original Investigation

DOI: 10.1007/s00439-008-0584-7

Cite this article as:
Costas, J., Carrera, N., Domínguez, E. et al. Hum Genet (2009) 124: 607. doi:10.1007/s00439-008-0584-7

Abstract

The number and frequency of susceptibility alleles at loci associated to most psychiatric disorders is largely unknown, in spite of its relevance for the design of studies aiming to find these alleles. Both, common polymorphisms and rare mutations may contribute to the genetic susceptibility to complex psychiatric disorders, being the relative relevance of each type of variation currently under debate. Here, we confirmed the existence of a common protective haplotype against schizophrenia at the dopamine D3 receptor (DRD3) gene, by replication and pooled analysis with previous data (Mantel–Haenszel χ2P value = 0.00227; OR = 0.79, 95% CI 0.68–0.92, based on 794 cases and 1,078 controls from three independent populations of European origin). This protective haplotype is at very low frequency in Sub-Saharan Africans (median 0.06) and at intermediate frequencies in other populations (median 0.25). We also revealed, by examining the patterns of linkage disequilibrium around this gene, that the protective haplotype has reached high frequency in non-African populations due to selection acting, most probably, on a linked functional polymorphism, the non-synonymous single nucleotide polymorphism Ser9Gly (rs6280), also at DRD3. Thus, this finding shows that the natural selection may play a role in the existence of common alleles conferring different susceptibility to schizophrenia.

Supplementary material

439_2008_584_MOESM1_ESM.doc (34 kb)
Supplementary Table (DOC 34 kb)

Copyright information

© Springer-Verlag 2008