Abstract:

Several genome-wide linkage studies have suggested linkage between markers on the long arm of chromosome 22 and schizophrenia. It has also been reported that 22q11.2 deletions increase the risk of schizophrenia. Therefore, 22q is a candidate region for schizophrenia. To search for genetic susceptibility loci for schizophrenia on 22q, we conducted a three-stage case-control association study in Japanese individuals. In the first stage, we examined 13 microsatellite markers on 22q in 766 individuals (340 patients with schizophrenia and 426 control individuals) and found a potential association of AFM262VH5 (D22S283) with schizophrenia. In the second stage, we performed fine mapping of the myosin heavy chain 9, non-muscle (MYH9) gene, where AFM262VH5 is located, using 25 tagging single nucleotide polymorphisms (SNPs). We obtained potential associations between three SNPs in MYH9 and schizophrenia in 1193 individuals (595 patients and 598 controls), which included the individuals analyzed in the first stage. In the third stage, however, we could not replicate these associations in 4694 independent individuals (2288 patients and 2406 controls). Our results suggest that MYH9 does not confer increased susceptibility to schizophrenia in the Japanese population, although we could not exclude possible contributions of other genes on 22q to the pathogenesis of schizophrenia.

日本語要旨:

統合失調症患者340名と健常対象者426名において、13個の22ｑのマイクロサテライトマーカーとMYH9遺伝子内のSNPとの相関を認め、次いでMYH9遺伝子内の25個のタグSNPを統合失調症患者595名と健常対象者598名でタイピングしたところ、相関を認めた。しかし別の統合失調症患者228名と健常対象者2406名では有意な差を認めなかった。しかし、22ｑ領域の別の遺伝子が統合失調症と何らかの関係があることを否定できない。