We carried out genome-wide association (GWA) analysis for atopic dermatitis case/control status in 26 individual studies (Supplementary Table 1), comprising a total of 21,399 cases and 95,464 controls. The majority of these studies included individuals of only European ancestry (22 studies, 18,900 cases, 84,166 controls). We also included one study of Japanese individuals (RIKEN, 1,472 cases. 7,966 controls), one study of African American individuals (SAPPHIRE, 422 cases and 844 controls), one study of Latin American individuals (GALA II, 300 cases, 1,592 controls) and one study with individuals of mixed non-European ancestry (Generation R, 305 cases, 896 controls).
Each cohort separately imputed their genetic data to 1000 Genomes Project Phase 1 (the majority to the March 2012 release, Supplementary Table 1) and carried out GWA analysis across all imputed variants. Before meta-analysis we restricted each study to only those variants with minor allele frequency (MAF)>1% and moderate imputation quality score (Rsq>0.3 for variants imputed in MACH and proper info>0.4 for IMPUTE). For some cohorts additional quality control filters were applied (full methods for each study are available in Supplementary Note 1).
Meta-analysis was conducted for Europeans only in GWAMA (using fixed effects) and for all ethnicities combined in MANTRA60 . Rather than imposing a fixed or random effects model, MANTRA accounts for the heterogeneity of effects between ethnicities by allowing the studies to cluster according to allele frequency profile (and hence population genetic similarity). To prevent very small European studies (with less precise estimates of the allele frequencies) from having undue weight in our analysis we fixed the Europeans to cluster together by using the European fixed effects results in the MANTRA analysis. Variants with p<5×10−8 in the European analysis were considered to be associated, as were any additional variants with (log10) Bayes Factor (BF)>6.1 (equivalent to p<5×10−8)61 in the MANTRA analysis. Each locus is represented in the results table by the variant with the strongest evidence for association. Heterogeneity was assessed using the I2 statistic and Cochrane’s Q test. Meta-analysis results were also stratified according to ethnicity, method of case diagnosis and age of onset to explore sources of heterogeneity.
For the Epidermal-differentiation complex region (where the FLG gene is located and which has previously shown complex association results), we repeated the association tests (across the region between 150.2–154.5Mb on chromosome 1) conditioning on the four most common FLG variants (R501X, 2282del4, R2447X, S3247X) in the individual studies where these were available (10 studies, 20,384 individuals, Supplementary Table 12). These were meta-analyzed to identify whether there were any remaining independent association signals in this region.
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