Journal article
Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX
The New England journal of medicine, v 358(9), pp 900-909
28 Feb 2008
PMID: 18204098
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease in which the risk of disease is influenced by complex genetic and environmental contributions. Alleles of HLA-DRB1, IRF5, and STAT4 are established susceptibility genes; there is strong evidence for the existence of additional risk loci.
Methods We genotyped more than 500,000 single-nucleotide polymorphisms (SNPs) in DNA samples from 1311 case subjects with SLE and 1783 control subjects; all subjects were North Americans of European descent. Genotypes from 1557 additional control subjects were obtained from public data repositories. We measured the association between the SNPs and SLE after applying strict quality-control filters to reduce technical artifacts and to correct for the presence of population stratification. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden.
Results Genetic variation in the region upstream from the transcription initiation site of the gene encoding B lymphoid tyrosine kinase (BLK) and C8orf13 (chromosome 8p23.1) was associated with disease risk in both the U.S. and Swedish case-control series (rs13277113; odds ratio, 1.39; P=1 x 10(-10)) and also with altered levels of messenger RNA in B-cell lines. In addition, variants on chromosome 16p11.22, near the genes encoding integrin alpha M (ITGAM, or CD11b) and integrin alpha X (ITGAX), were associated with SLE in the combined sample (rs11574637; odds ratio, 1.33; P=3 x 1 (-11)).
Conclusions We identified and then confirmed through replication two new genetic loci for SLE: a promoter-region allele associated with reduced expression of BLK and increased expression of C8orf13 and variants in the ITGAM-ITGAX region.
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Details
- Title
- Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX
- Creators
- Geoffrey Hom - GenentechRobert R. Graham - GenentechBarmak Modrek - GenentechKimberly E. Taylor - Univ Calif San Francisco, San Francisco, CA 94143 USAWard Ortmann - GenentechSophie Garnier - Uppsala UniversityAnnette T. Lee - Northwell HealthSharon A. Chung - University of California, San FranciscoRicardo C. Ferreira - GenentechP. V. Krishna Pant - PerlegenDennis G. Ballinger - PerlegenRoman Kosoy - University of California, DavisF. Yesim Demirci - University of PittsburghM. Ilyas Kamboh - University of PittsburghAmy H. Kao - University of PittsburghChao Tian - University of California, DavisIva Gunnarsson - Karolinska InstitutetAnders A. Bengtsson - Lund UniversitySolbritt Rantapaa-Dahlqvist - Umeå UniversityMichelle Petri - Johns Hopkins UniversitySusan Manzi - University of PittsburghMichael F. Seldin - Institute of Molecular MedicineLars Ronnblom - Uppsala UniversityAnn-Christine Syvanen - Uppsala UniversityLindsey A. Criswell - University of California, San FranciscoPeter K. Gregersen - Northwell HealthTimothy W. Behrens - Genentech
- Publication Details
- The New England journal of medicine, v 358(9), pp 900-909
- Publisher
- Massachusetts Medical Soc
- Number of pages
- 10
- Grant note
- M01RR000052 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) R01AR050267 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) HL54900; HL74165 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) N01-AI95386 / NIAID NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01HL074165 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) N01AI095386 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) M01-RR00052; 5-M01-RR00079 / NCRR NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) P60 AR053308; K24-AR02175; K23-AR051044; N01-AR1-2256; R01-AR44804; AR43737; R01-AR046588; AR050267 / NIAMS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000253430200005
- Scopus ID
- 2-s2.0-40049108936
- Other Identifier
- 991021934011804721
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- Industry collaboration
- Domestic collaboration
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- Web of Science research areas
- Medicine, General & Internal