Contributions
Abstract: EP1460
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
Background: Many associated variants were detected in multiple sclerosis (MS) from genome-wide association studies (GWAS). However, not much is known about the biological effect of each variant and difference of associated tissues among races.
Objective: To reveal specific tissues where the associated genes with Japanese MS are more densely interconnected than expected and clarify difference of associated tissues between Japanese and European descent MS.
Methods: GWAS was conducted in 533 Japanese patients with MS and 1,789 controls. After converting variant p values into gene p values, the values except for the MHC region were applied to tissue-specific regulatory networks which were composed by merging transcription factor sequence motifs with promoter/enhancer activity data from the FANTOM5 project (Marbach D, et al. Nat Methods, 2016). Interconnectivities were compared with index calculated in the same way for 10,000 permutations of the ranked gene list. Those enrichment scores were compared with ones calculated by using GWAS results in European descent MS.
Results: In 32 high level regulatory networks, genes associated with Japanese MS were densely interconnected in networks of neurons and fetal brain, connective tissue, lymphocytes, connective tissue and integumental cells, and lymphoma (FDR corrected p value < 0.05). On the other hand, any specific networks were detected by using genes associated with European-descent MS. Among networks of lymphocytes, the associated genes were most interconnected in the network of natural killer cells (FDR corrected p = 0.00070).
Conclusions: The associated genes were functionally different between Japanese and European descent MS from the view point of tissue specific regulatory network.
Disclosure: Takuya Matsushita has received grant support from JSPS Kakenhi and received speaker honoraria payments from Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Company and Biogen Japan.
Ken Yamamoto: nothing to disclose
Yuri Nakamura: nothing to disclose
Mitsuru Watanabe has received grant support from Japan Society for the Promotion of Science, Japan (JSPS KAKENHI Grant Number 17K16124) and GlaxoSmithKline.
Koji Shinoda: nothing to disclose
Noriko Isobe received grant support from JSPS Kakenhi 18K07529, Japan Intractable Disease research Foundation, Mitsubishi Tanabe Pharma, Bayer Yakuhin, Ltd., and Japan Blood Products Organization.
Jun-ichi Kira has received grants, consultant fees, speaking fees and/or honoraria from AMED, Health, Labour and Welfare Sciences Research Grants, MEXT KAKENHI, JSPS KAKENHI, Novartis Pharma, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Teijin Pharma, Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Astellas Pharma, Pfizer Japan, Eisai.
Abstract: EP1460
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
Background: Many associated variants were detected in multiple sclerosis (MS) from genome-wide association studies (GWAS). However, not much is known about the biological effect of each variant and difference of associated tissues among races.
Objective: To reveal specific tissues where the associated genes with Japanese MS are more densely interconnected than expected and clarify difference of associated tissues between Japanese and European descent MS.
Methods: GWAS was conducted in 533 Japanese patients with MS and 1,789 controls. After converting variant p values into gene p values, the values except for the MHC region were applied to tissue-specific regulatory networks which were composed by merging transcription factor sequence motifs with promoter/enhancer activity data from the FANTOM5 project (Marbach D, et al. Nat Methods, 2016). Interconnectivities were compared with index calculated in the same way for 10,000 permutations of the ranked gene list. Those enrichment scores were compared with ones calculated by using GWAS results in European descent MS.
Results: In 32 high level regulatory networks, genes associated with Japanese MS were densely interconnected in networks of neurons and fetal brain, connective tissue, lymphocytes, connective tissue and integumental cells, and lymphoma (FDR corrected p value < 0.05). On the other hand, any specific networks were detected by using genes associated with European-descent MS. Among networks of lymphocytes, the associated genes were most interconnected in the network of natural killer cells (FDR corrected p = 0.00070).
Conclusions: The associated genes were functionally different between Japanese and European descent MS from the view point of tissue specific regulatory network.
Disclosure: Takuya Matsushita has received grant support from JSPS Kakenhi and received speaker honoraria payments from Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Company and Biogen Japan.
Ken Yamamoto: nothing to disclose
Yuri Nakamura: nothing to disclose
Mitsuru Watanabe has received grant support from Japan Society for the Promotion of Science, Japan (JSPS KAKENHI Grant Number 17K16124) and GlaxoSmithKline.
Koji Shinoda: nothing to disclose
Noriko Isobe received grant support from JSPS Kakenhi 18K07529, Japan Intractable Disease research Foundation, Mitsubishi Tanabe Pharma, Bayer Yakuhin, Ltd., and Japan Blood Products Organization.
Jun-ichi Kira has received grants, consultant fees, speaking fees and/or honoraria from AMED, Health, Labour and Welfare Sciences Research Grants, MEXT KAKENHI, JSPS KAKENHI, Novartis Pharma, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Teijin Pharma, Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Astellas Pharma, Pfizer Japan, Eisai.