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Objective Genome-wide association studies (GWAS) in individuals of European ancestry identified a number of systemic lupus erythematosus (SLE) susceptibility loci using earlier versions of high-density genotyping platforms. Followup studies on suggestive GWAS regions using larger samples and more markers identified additional SLE loci in subjects of European descent. This multistage study was undertaken to identify novel SLE loci. Methods In stage 1, we conducted a new GWAS of SLE in a North American case-control sample of subjects of European ancestry (n = 1,166) genotyped on Affymetrix Genome-Wide Human SNP Array 6.0. In stage 2, we further investigated top new suggestive GWAS hits by in silico evaluation and meta-analysis using an additional data set of subjects of European descent (>2,500 individuals), followed by replication of top meta-analysis findings in another data set of subjects of European descent (>10,000 individuals) in stage 3. Results As expected, our GWAS revealed the most significant associations at the major histocompatibility complex locus (6p21), which easily surpassed the genome-wide significance threshold ( P < 5 × 10−8). Several other SLE signals/loci previously implicated in Caucasians and/or Asians were also confirmed in the stage 1 discovery sample, and the strongest signals were observed at 2q32/ STAT4 ( P = 3.6 × 10−7) and at 8p23/ BLK ( P = 8.1 × 10−6). Stage 2 meta-analyses identified a new genome-wide significant SLE locus at 12q12 (meta P = 3.1 × 10−8), which was replicated in stage 3. Conclusion Our multistage study identified and replicated a new SLE locus that warrants further followup in additional studies. Publicly available databases suggest that this newly identified SLE signal falls within a functionally relevant genomic region and near biologically important genes. [ABSTRACT FROM AUTHOR]

Background. The persistent presence of antiphospholipid antibodies (APA) may lead to the development of primary or secondary antiphospholipid syndrome. Although the genetic basis of APA has been suggested, the identity of the underlying genes is largely unknown. In this study, we have performed a genome-wide association study (GWAS) in an effort to identify susceptibility loci/genes for three main APA: anticardiolipin antibodies (ACL), lupus anticoagulant (LAC), and anti-β2 glycoprotein I antibodies (anti-β2GPI). Methods. DNA samples were genotyped using the Affymetrix 6.0 array containing 906,600 single-nucleotide polymorphisms (SNPs). Association of SNPs with the antibody status (positive/negative) was tested using logistic regression under the additive model. Results. We have identified a number of suggestive novel loci with P < E - 05. Although they do not meet the conservative threshold of genome-wide significance, many of the suggestive loci are potential candidates for the production of APA. We have replicated the previously reported associations of HLA genes and APOH with APA but these were not the top loci. Conclusions.We have identified a number of suggestive novel loci for APA that will stimulate follow-up studies in independent and larger samples to replicate our findings. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the prevalence of adult systemic lupus erythematosus (SLE) in California and Pennsylvania in 2000. A method that combines data on the frequency with which patients are hospitalized with data from state inpatient hospital databases to estimate the prevalence of SLE was used. It found that the use of hospitalization databases does not allow for verification of diagnoses of SLE and more accurate estimates would be obtained using hospitalization frequencies from a population-based sample of patients with SLE.