OMRF SLEGEN GWAS Data from European-American Women with Lupus

"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." Reprinted from Nature Genetics, 2008 Feb; 40(2):204-10, PMID:18204446, with permission from Nature Publishing Group. Data submitted to dbGaP includes 297 samples from Oklahoma. (Please see also Study Accession: phs000216.v1.p1)]]>
Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families. We performed a genome-wide association scan using 317,501 SNPs on the Illumina HumanHap300 genotyped at the Broad Institute. The samples submitted to dbGap represent the admixture trimmed set of 706 female cases and 353 controls on 308,330 SNPs that passed quality control. The number of controls differs from what was published because of the use of 1,964 out of study controls: 1,848 Illumina controls and 116 IBD controls.Case Inclusion To be enrolled as an affected, an individual is required to have a diagnosis that satisfies the 1982 American College of Rheumatology's criteria for the classification SLE as revised in 1997. Case Exclusion Exclusion of affecteds will include the following criteria: Concurrent illness sufficient to preclude study participation. Known current pregnancy. Inability to provide consent. Inability to cooperate with the study. Prisoners or wards of the state. Inclusion and Exclusion of Family Members and Controls Inclusion of family members requires that the family member is a 1st or 2nd degree relative of the affected, has not been diagnosed with SLE, and will provide informed consent. Failure or inability to provide consent or cooperation will exclude family members from study participation. Control Inclusion Controls will be included in the study if they can be matched to a specific case on the basis of sex, age (± 5 years), and self-identified racial group, provide consent, and have the ability to cooperate with the study. Control Exclusion Controls would be excluded from the study if there is a known current pregnancy or a diagnosis or alleged diagnosis of Sjögren's, systemic lupus erythematosus, rheumatoid arthritis, scleroderma, dermatomyositis, primary biliary cirrhosis, lymphoma, HIV, or polymyositis has been made. Other Subject Population Considerations The subject population will not be selected with regard to racial, ethnic, or gender composition, with the exception that the contract does specify that at least 40% of the families enrolled must be considered from minority populations since studies for lupus suggest that linkages to lupus appear to act more dominantly in one ethnic group. Also, lupus is a female dominated disease, with over 90% of the cases affecting women. Therefore, there is strong support for the effort to include multiple minority populations in the subject groups. Since multiplex pedigrees are being enrolled, a wide range of subject ages will also be included in the study. Although SLE is rare among children, pediatric SLE patients will be included in the study with consent of their parents. Vulnerable special classes of subjects such as fetuses and women known to be pregnant will be excluded from the study. Prisoners and institutionalized individuals will not be routinely recruited and will require the representation of their advocate.]]>
In 2005, the International Lupus Genetics Consortium (SLEGEN) was formed under the sponsorship of the Alliance for Lupus Research (ALR) and is now a productive multi-institutional consortium of nine world renowned lupus investigators. SLEGEN has successfully conducted a genome-wide association study with independent replication in European-derived populations and has both confirmed previous candidate genes and discovered multiple new genetic effects. Of the 3057 total samples included in the SLEGEN GWAS, 308 were enrolled into the Lupus Family Registry and Repository (LFRR) (http://lupus.omrf.org) and the Lupus Genetics Studies at the Oklahoma Medical Research Foundation in Oklahoma City, Oklahoma. The LFRR operates a research resource facility of >1500 well characterized pedigrees both multiplex and simplex for systemic lupus erythematosus, maintains a repository of DNA, sera, plasma, cell lines and data, and is a resource that supports basic and clinical research in lupus, genetics and other disciplines.]]>