Large-scale replication study to identify susceptibility loci for systemic lupus erythematosus (SLE). A custom SNP array (Illumina Infinium II) consisting of 12,864 variants selected from 2,466 regions that showed nominal evidence of association to SLE was designed. Two independent SLE case and control populations from the United States (1,129 SLE cases and 2,991 controls) and Sweden (834 SLE cases and 1,338 controls) were genotyped. Further evidence of association with SLE for 21 of the variants was obtained, including 9 loci that reached genome-wide significance in the combined dataset. To identify previously unknown SLE risk loci, 3,188 SNPs from 2,446 distinct loci that showed evidence of association to SLE were examined in the genome-wide dataset - which comprised 502,033 SNPs genotyped in 1,310 SLE cases and an expanded set of 7,859 controls. Using this dataset, IMPUTE version 1 was used to infer genotypes using HapMap Phase II CEU samples as a reference. This identified five new SLE risk loci with a combined P value that exceeded the genome-wide threshold for significance.
US data. 1,464 cases and 3,078 controls were genotyped on the custom 12K chip. 116 individuals were excluded who had >5% missing data and 279 individuals based on cryptic relatedness and duplicate samples based on identity-by-state status (PI_Hat > 0.15). Only SNPs with <5% missing data, Hardy-Weinberg equilibrium P value > 1 10-6, minor allele frequency > 0.01% and P > 1 10-5 in a test for differential missingness between cases and controls were included. After applying the above filters, 1,144 cases and 3,003 controls and 11,024 SNPs were available for analysis.
Swedish data. A set of 888 cases and 527 controls genotyped on the custom 12K chip was available for analysis. A separate set of 1,115 Swedish controls genotyped on the 317K Illumina chip was also incorporated into the analysis. The following steps were used to combine the two datasets: (i) an overlapping set of 6,789 SNPs between the 12K and 317K data was created to examine the Swedish replication cohort for cryptic relatedness and duplicate samples. As a result, 313 samples were excluded (PI_Hat > 0.15). After quality control checks, 863 cases and 523 controls were genotyped on the custom 12K chip and 831 controls genotyped on the 317K chip, (ii) the 831 Swedish controls genotyped with the 317K array were imputed to create a final set of 11,394 overlapping SNPs. The SNPs in this dataset were filtered using the same thresholds as described above.
GDXHsS00015 meets the following criteria: