期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 88, 期 1, 页码 83-91出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2010.11.014
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资金
- NCATS NIH HHS [UL1 TR000154] Funding Source: Medline
- NCRR NIH HHS [P30 RR031152-01, P30 RR031152, UL1 RR025741, UL1 RR025014] Funding Source: Medline
- NIAID NIH HHS [K24 AI078004, R21 AI070304] Funding Source: Medline
- NIAMS NIH HHS [R01 AR043814-13, P30 AR053483, R01 AR051545, R01 AR043814, P60 AR053308] Funding Source: Medline
- NIGMS NIH HHS [P30 GM103510] Funding Source: Medline
Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 x 10(-8)) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 x 10(-8), OR = 0.83) and rs387619 (p = 7.7 x 10(-7), OR = 0.83) in the European samples with p(meta) = 1.82 x 10(-9) for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 x 10(-3), OR = 0.81 and p = 4.3 x 10(-4), OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p(meta) = 2.36 x 10(-13). This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.
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