
DOI . ORG {
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Title[redir]:
Cumulative association of eight susceptibility genes with systemic lupus erythematosus in a Japanese female population | Journal of Human Genetics
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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Keywords {🔍}
risk, alleles, article, sle, lupus, google, scholar, susceptibility, systemic, association, erythematosus, study, japanese, number, patients, allele, genetic, cas, carrying, controls, genes, cumulative, individuals, nature, population, loci, healthy, japan, genet, ito, analysis, data, human, gene, arthritis, polymorphism, university, table, female, kawasaki, subjects, disorder, compared, rheumatology, model, disease, size, clinical, tnfsf, polymorphisms,
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nature portfolio scientific research permissions reprints privacy policy nature advertising research ethics committees social media large-scale international collaboration large-scale studies established genetic risk score genetic epidemiology laboratory development research purpose research genome-wide snp arrays author correspondence genome-wide association scan pcr-microtiter plate hybridization apparent gene–gene interaction systemic lupus erythematosus high-density snp screening significant gene–gene interaction permissions strong genetic predisposition full size image common genetic variants estimate genetic predisposition genome-wide association study low genetic predisposition fcγ receptor iib human april gene japan rheumatism foundation rheumatology revised criteria cell receptor signaling single nucleotide polymorphism privacy efficiently distinguish groups explore content similar content early disease onset case-control association study low risk groups yoshinari takasaki exclude potential influence additional risk allele statistically significant association risk allele count genetic risk factor higher genetic risk
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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 à 10â12). Significant geneâgene 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 11â13 risk alleles were 4.17 (95% confidence interval (CI) 1.89â9.19, P=0.0002) and 8.77 (95% CI 1.92â40.0, P=0.0016), respectively. In contrast, subjects with ⩽4 risk alleles were significantly decreased in SLE (OR 0.15, CI 0.03â0.67, 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 1.09â4.83, 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.
datePublished:2011-05-12T00:00:00Z
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Epidemiology
Genetic predisposition to disease
Systemic lupus erythematosus
genetic risk score
polymorphism
susceptibility
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Human Genetics
Molecular Medicine
Gene Function
Gene Expression
Gene Therapy
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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 à 10â12). Significant geneâgene 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 11â13 risk alleles were 4.17 (95% confidence interval (CI) 1.89â9.19, P=0.0002) and 8.77 (95% CI 1.92â40.0, P=0.0016), respectively. In contrast, subjects with ⩽4 risk alleles were significantly decreased in SLE (OR 0.15, CI 0.03â0.67, 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 1.09â4.83, 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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Genetic predisposition to disease
Systemic lupus erythematosus
genetic risk score
polymorphism
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Human Genetics
Molecular Medicine
Gene Function
Gene Expression
Gene Therapy
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