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Su Ying; John Burke, MB; F. Anthony O'Neill, MD; Bernadette Murphy, MB; Li Nie, MD, MS; Barbara Kipps; Joseph Bray, MB; Rosmarie Shinkwin, MB; Maurin Ni Nuallain, MB; Charles J. MacLean, PhD; Dermot Walsh, MB, FRCPI; Scott R. Diehl, PhD; Kenneth S. Kendler, MD

Arch Gen Psychiatry. 1993;50(3):205-211.

Abstract
• A leading theory hypothesizes that schizophrenia arises from dysregulation of the dopamine system in certain brain regions. As this dysregulation could arise from abnormal expression of D₂ dopamine receptors, the D₂ receptor gene (DRD2) on chromosome 11q is a candidate locus for schizophrenia. We tested whether allelic variation at DRD2 and five surrounding loci cosegregated with schizophrenia in 112 small- to moderate-size Irish families containing two or more members affected with schizophrenia or schizoaffective disorder, defined by DSM-III-R. Evidence of linkage was assessed using varying definitions of illness and modes of transmission. Assuming genetic homogeneity, linkage between schizophrenia and large regions of 11q around DRD2 could be strongly excluded. Assuming genetic heterogeneity, variation at the DRD2 locus could be rejected as a major risk factor for schizophrenia in more than 50% of these families for all models tested and in as few as 25% of the families for certain models. The DRD2 linkage in fewer than 25% of these families could not be excluded under any of the models tested. Our results suggest that the major component of genetic susceptibility to schizophrenia is not due to allelic variation at the DRD2 locus or other genes in the surrounding chromosomal region.

Author Affiliations
From the Departments of Human Genetics and Psychiatry (Drs Su, Nie, MacLean, Diehl, and Kendler, and Ms Kipps), Medical College of Virginia/Virginia Commonwealth University, Richmond; the Health Research Board, Dublin, Ireland (Drs Burke, Murphy, Bray, Shinkwin, Ni Nuallain, and Walsh); and the Department of Psychiatry, Queens University Belfast, Ireland (DrÖNeill).

Footnotes
Accepted for publication June 4, 1992.

Reprint requests to Department of Psychiatry, MCV, Box 710, Richmond VA 23298 (Dr Kendler).

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