| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Research Abstract |
Whole genome association analysis (WGA) is a potentially powerful means of identifying the common variants that underlie complex traits. The promise of this technique has become a reality through the rapid development of high-throughput SNP genotyping technology. However, interpretation of the resulting data requires great care, since larger sample sizes may be required to detect small-to-modest effect alleles with high level of significance. Conversely, a small number of genuine causal variants will be buried within a larger number of false-positive associations. Therefore, follow-up studies such as multi-stage approaches are necessary to distinguish the small number of genuine causal variants from the high proportion of false-positive associations.
Here, we performed a three-tired stage screening to identify susceptibility genes for schizophrenia. For tier 1, 120 trio samples from Japanese schizophrenic pedigrees were genotyped using-an AffymetrixGeneChip Mapping 100K Array. All subje
… More
cts resided in central Japan. Transmission distortions in the family panel were evaluated using the transmission disequilibrium test (TDT). We genotyped 115, 700 SNP markers, of which 17, 807 SNPs were not polymorphic in our Japanese samples and excluded from further analyses. For tier 2, we selected 1, 536 SNPs from the result of tire 1, and successfully genotyped 1, 496 SNPs in Japanese case-control samples (506 samples vs. 506 samples) by using illumina BeadArray technology. We identified 70 SNPs that were associated with Japanese schizophrenia in both tier 1 (P<0.01) and tier 2 (P<0.05) samples. For tier 3, confirmation study for 70 SNPs was performed by 293 NIMH Chinese pedigree samples (1, 163 individuals).
In this study, we represent the multi-stage approaches to identify susceptibility genes for schizophrenia. Our study will provide useful information for the future genetic study of schizophrenia, and careful justification by independent replication across population will clarify the genuine genes that contribute to the pathogenesis of schizophrenia. Less
|
