Cytogenetic location: 8p23.1 Genomic coordinates (GRCh38) : 8:6,300,001-12,800,000
For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700.
Hom et al. (2008) performed a genomewide association study involving more than 500,000 SNPs in DNA samples from 1,311 case subjects with SLE and 1,783 control subjects; all subjects were North Americans of European descent. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden. The A allele of a single-nucleotide polymorphism on chromosome 8p23.1, rs13277113, was highly enriched in the sample from United States case subjects as compared with controls (P = 8 x 10(-8); combined OR, 1.39; 95% CI, 1.26-1.54). An association was also observed in the Swedish replication set (P = 4 x 10(-4); OR, 1.33; 95% CI, 1.13-1.55). A combined analysis of rs13277113 with both the United States and Swedish samples showed P = 1 x 10(-10). The SNP rs13277113 maps to the interval between 2 genes transcribed in opposite directions: BLK (191305), a tyrosine kinase in the Src family that signals downstream of the B cell receptor, and C8ORF13 (FAM167A; 610085). Homozygotes for the A allele of rs13277113 had levels of BLK mRNA expression that were approximately 50% of those of homozygotes for the G allele. The expression of the C8ORF13 gene also correlated with the rs13277113 SNP, but in the opposite direction. The A allele was associated with higher expression of C8ORF13, whereas the G allele was significantly associated with lower expression. A/G heterozygotes had intermediate levels of expression of both genes.
Han et al. (2009) performed a genomewide association study of SLE in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina-Human610-Quad BeadChips and replicating 78 SNPs in 2 additional cohorts (3,152 cases and 7,050 controls). Han et al. (2009) found association with 3 SNPs at the BLK gene. The strongest association was with rs7812879 (combined P value = 2.09 x 10(-24), odds ratio = 0.69, 95% confidence interval 0.64-0.74).
Han, J.-W., Zheng, H.-F., Cui, Y., Sun, L.-D., Ye, D.-Q., Hu, Z., Xu, J.-H., Cai, Z.-M., Huang, W., Zhao, G.-P., Xie, H.-F., Fang, H., and 55 others. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nature Genet. 41: 1234-1237, 2009. [PubMed: 19838193, related citations] [Full Text]
Hom, G., Graham, R. R., Modrek, B., Taylor, K. E., Ortmann, W., Garnier, S., Lee, A. T., Chung, S. A., Ferreira, R. C., Pant, P. V. K., Ballinger, D. G., Kosoy, R., and 15 others. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. New Eng. J. Med. 358: 900-909, 2008. [PubMed: 18204098, related citations] [Full Text]
DO: 9074;
Cytogenetic location: 8p23.1 Genomic coordinates (GRCh38) : 8:6,300,001-12,800,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 8p23.1 | {Systemic lupus erythematosus, susceptibility to, 12} | 612254 | 2 |
For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700.
Hom et al. (2008) performed a genomewide association study involving more than 500,000 SNPs in DNA samples from 1,311 case subjects with SLE and 1,783 control subjects; all subjects were North Americans of European descent. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden. The A allele of a single-nucleotide polymorphism on chromosome 8p23.1, rs13277113, was highly enriched in the sample from United States case subjects as compared with controls (P = 8 x 10(-8); combined OR, 1.39; 95% CI, 1.26-1.54). An association was also observed in the Swedish replication set (P = 4 x 10(-4); OR, 1.33; 95% CI, 1.13-1.55). A combined analysis of rs13277113 with both the United States and Swedish samples showed P = 1 x 10(-10). The SNP rs13277113 maps to the interval between 2 genes transcribed in opposite directions: BLK (191305), a tyrosine kinase in the Src family that signals downstream of the B cell receptor, and C8ORF13 (FAM167A; 610085). Homozygotes for the A allele of rs13277113 had levels of BLK mRNA expression that were approximately 50% of those of homozygotes for the G allele. The expression of the C8ORF13 gene also correlated with the rs13277113 SNP, but in the opposite direction. The A allele was associated with higher expression of C8ORF13, whereas the G allele was significantly associated with lower expression. A/G heterozygotes had intermediate levels of expression of both genes.
Han et al. (2009) performed a genomewide association study of SLE in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina-Human610-Quad BeadChips and replicating 78 SNPs in 2 additional cohorts (3,152 cases and 7,050 controls). Han et al. (2009) found association with 3 SNPs at the BLK gene. The strongest association was with rs7812879 (combined P value = 2.09 x 10(-24), odds ratio = 0.69, 95% confidence interval 0.64-0.74).
Han, J.-W., Zheng, H.-F., Cui, Y., Sun, L.-D., Ye, D.-Q., Hu, Z., Xu, J.-H., Cai, Z.-M., Huang, W., Zhao, G.-P., Xie, H.-F., Fang, H., and 55 others. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nature Genet. 41: 1234-1237, 2009. [PubMed: 19838193] [Full Text: https://doi.org/10.1038/ng.472]
Hom, G., Graham, R. R., Modrek, B., Taylor, K. E., Ortmann, W., Garnier, S., Lee, A. T., Chung, S. A., Ferreira, R. C., Pant, P. V. K., Ballinger, D. G., Kosoy, R., and 15 others. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. New Eng. J. Med. 358: 900-909, 2008. [PubMed: 18204098] [Full Text: https://doi.org/10.1056/NEJMoa0707865]
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