| Project/Area Number |
15H04805
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
木内 喜孝 東北大学, 高度教養教育・学生支援機構, 教授 (20250780)
黒羽 正剛 東北大学, 大学病院, 助教 (70709469)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | 炎症性腸疾患 / クローン病 / 疾患感受性遺伝子 / 潰瘍性大腸炎 / 遺伝学 / 消化器内科学 / 感受性遺伝子 |
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| Outline of Final Research Achievements |
Several GWASs revealed more than 200 susceptibility loci for IBD. We built a 1KJPN panel containing genomic variations obtained by whole-genome resequencing of 1070 Japanese individuals,and developed the Japonica Array optimized for genotyping and imputing the Japanese population. To clarify the Japanese-specific genetic background of Crohn’s disease (CD), we performed GWAS using a population-optimized SNP array and imputation.
Genotyping data of 7,934,670 SNPs from 737 Japanese CD patients and 2188 controls were analyzed. SNPs located in three known loci, TNFSF15, MHC, and ZNF365, 4p14 showed significant associations with CD. Locus rs488200, located on an intron of RAP1A, was the top hit of novel candidate loci (p=8.85E-8, OR=1.43). A previous report indicated that the underexpression of the RAP1A gene increases the risk of CD because Rap1 regulates T-cell circulation, thereby preventing the onset of colitis in a mouse model. RAP1A is a novel candidate susceptibility gene for CD.
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