Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci
Open accessAbstract
Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.
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A substantial genetic contribution to SLE risk is conferred by MHC gene(s) on chromosome 6p21.
“A substantial genetic contribution to systemic lupus erythematosus (SLE) risk is conferred by major histocompatibility complex (MHC) gene(s) on chromosome 6p21.”
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References 29 · Cited by 1,309
- Authors
- The International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley, J. B., Alarcón-Riquelme, M. E., Criswell, L. A., Jacob, C. O., Kimberly, R. P., Moser, K. L., Tsao, B. P., Vyse, T. J., & Langefeld, C. D.
- Affiliations
- United States Department of Veterans Affairs (US)
- Uppsala University (SE)
- University of California, San Francisco (US)
- University of Southern California (US)
- University of Alabama at Birmingham (US)
- University of Minnesota (US)
- University of California, Los Angeles (US)
- Hammersmith Hospital (GB)
- Wake Forest University Health Sciences (US)
- Corresponding author
- Harley, John B
- Langefeld, Carl D
- ORCID
- Venue
- Nature Genetics
- Published
- 2008-01-20
- Volume
- 40
- Issue
- 2
- Pages
- 204-210
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3712260
- OpenAlex
- W2010160850
- Cited by
- 1,309
- References
- 29
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 39 · 2023: 33 · 2022: 49 · 2021: 49 · 2020: 41 · 2019: 65 · 2018: 49 · 2017: 67 · 2016: 67 · 2015: 81 · 2014: 87 · 2013: 87 · 2012: 118
- FWCI
- 100.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (051276)
- National Institutes of Health (n01ar62277-9-0-1, 6u54rr020278-06, 5r01ar043815-04)
- National Institute of Allergy and Infectious Diseases (AI-24717, R37AI024717, R01AI024717)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR033062, AR24260, AR-052300, P60AR053308, AR02175, R01AR052300, P30AR053483, N01-AR062277, AR43815, AR33062, AR22804, AR43247, K24AR002175, P01AR049084, AR49084, R01AR043814, AR43814)
- National Center for Research Resources (U54-RR020278, P20RR020143, RR-020143, RR020278)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Keywords
- systemic lupus erythematosus, genetic susceptibility, genome-wide association study, women, CD11b, HLA-DRB3, IRF5, FCGR2A, PTPN22, STAT4, autoimmune disease, European ancestry
- MeSH terms
- Alleles, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 6, Female, Genetic Markers, Haplotypes, HLA Antigens, Humans, Lupus Erythematosus, Systemic, Nerve Tissue Proteins, Risk Factors, ROC Curve, Genetic Variation, Cohort Studies, Linkage Disequilibrium, Genome, Human, Confidence Intervals, Logistic Models, Odds Ratio, Case-Control Studies, Protein Serine-Threonine Kinases, Area Under Curve, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, CD11b Antigen, White People, Intracellular Signaling Peptides and Proteins, STAT4 Transcription Factor, Interferon Regulatory Factors, Protein Tyrosine Phosphatase, Non-Receptor Type 22
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