GENOME SCAN OF SCHIZOPHRENIA

Objective: The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. Method: A genome wide map of 310 microsatellite DNA markers with average spacing of 11 centimorgans was genotyped in 269 individuals-126 of them with schizop hrenia-related psychoses-from 43 pedigrees. Nonparametric linkage anal ysis was used to assess the pattern of allele sharing at each marker l ocus relative to the presence of disease. Results: Nonparametric linka ge scores did not reach a genomewide level of statistical significance for any marker. There were five chromosomal regions in which empirica lly derived p values reached nominal levels of significance at eight m arker locations. There were p values less than 0.01 at chromosomes 2q (with the peak value in this region at D2S410) and 10q (D10S1239), and there were p values less than 0.05 at chromosomes 4q (D4S2623), 9q (D 9S257), and 11q (D11S2002). Conclusions: The results do not support th e hypothesis that a single gene causes a large increase in the risk of schizophrenia. The sample (like most others being studied for psychia tric disorders) has limited power to detect genes of small effect or t hose that are determinants of risk in a small proportion of families. All of the most positive results could be due to chance, or some could reflect weak linkage (genes of small effect). Multicenter studies may be useful in the effort to identify chromosomal regions most likely t o contain schizophrenia susceptibility genes.