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         headline:Cumulative association of eight susceptibility genes with systemic lupus erythematosus in a Japanese female population
         description:Although large-scale studies established many susceptibility genes to systemic lupus erythematosus (SLE), effect of each gene is not sufficiently large to be used alone to identify individuals with strong genetic predisposition. In this study, we analyzed the cumulative number of risk alleles at eight established susceptibility loci, HLA-DRB1, IRF5, STAT4, BLK, TNFAIP3, TNIP1, FCGR2B and TNFSF13, in 282 Japanese female SLE and 222 healthy female controls. The average number of risk alleles was significantly increased in SLE (8.07±1.60) than healthy controls (7.02±1.64) (P=1.63 × 10−12). Significant gene–gene interaction was not detected. When the subjects carrying seven risk alleles were used as a reference, the odds ratio (OR) for individuals carrying 10 and 11–13 risk alleles were 4.17 (95% confidence interval (CI) 1.89–9.19, P=0.0002) and 8.77 (95% CI 1.92–40.0, P=0.0016), respectively. In contrast, subjects with ⩽4 risk alleles were significantly decreased in SLE (OR 0.15, CI 0.03–0.67, P=0.007). The proportion of the patients with neurologic disorder was significantly increased in those carrying ⩾10 risk alleles than those with <10 (OR 2.30, CI 1.09–4.83, P=0.025). This study suggested that the cumulative number of risk alleles may efficiently distinguish groups with high and low genetic predisposition to SLE and its severe manifestation.
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      headline:Cumulative association of eight susceptibility genes with systemic lupus erythematosus in a Japanese female population
      description:Although large-scale studies established many susceptibility genes to systemic lupus erythematosus (SLE), effect of each gene is not sufficiently large to be used alone to identify individuals with strong genetic predisposition. In this study, we analyzed the cumulative number of risk alleles at eight established susceptibility loci, HLA-DRB1, IRF5, STAT4, BLK, TNFAIP3, TNIP1, FCGR2B and TNFSF13, in 282 Japanese female SLE and 222 healthy female controls. The average number of risk alleles was significantly increased in SLE (8.07±1.60) than healthy controls (7.02±1.64) (P=1.63 × 10−12). Significant gene–gene interaction was not detected. When the subjects carrying seven risk alleles were used as a reference, the odds ratio (OR) for individuals carrying 10 and 11–13 risk alleles were 4.17 (95% confidence interval (CI) 1.89–9.19, P=0.0002) and 8.77 (95% CI 1.92–40.0, P=0.0016), respectively. In contrast, subjects with ⩽4 risk alleles were significantly decreased in SLE (OR 0.15, CI 0.03–0.67, P=0.007). The proportion of the patients with neurologic disorder was significantly increased in those carrying ⩾10 risk alleles than those with <10 (OR 2.30, CI 1.09–4.83, P=0.025). This study suggested that the cumulative number of risk alleles may efficiently distinguish groups with high and low genetic predisposition to SLE and its severe manifestation.
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      name:Yoshinari Takasaki
      affiliation:
            name:Juntendo University
            address:
               name:Division of Rheumatology, Department of Internal Medicine, Juntendo University, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Hiroshi Hashimoto
      affiliation:
            name:Juntendo University School of Medicine
            address:
               name:Juntendo University School of Medicine, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Takayuki Sumida
      affiliation:
            name:Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
            address:
               name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
               type:PostalAddress
            type:Organization
      name:Naoyuki Tsuchiya
      affiliation:
            name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
            address:
               name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Kobe, Japan
      name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan
      name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Division of Rheumatology, Department of Internal Medicine, Juntendo University, Tokyo, Japan
      name:Division of Rheumatology, Department of Internal Medicine, Juntendo University, Tokyo, Japan
      name:Juntendo University School of Medicine, Tokyo, Japan
      name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

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