Data analysis and quality control (QC) was performed using the software packages R version 2.5.1 (http://www.R-project.org) and PLINK version 1.0.3.41 In the GWAS, genotype data were cleaned before analysis by removing SNPs or individuals that did not fulfil the QC criteria, which included: SNP call proportion ≥95%, subject completeness proportion ≥95%, SNP minor allele frequency ≥0.01 and SNP conformity with Hardy-Weinberg equilibrium expectations (p≥0.01 in controls). To correct for cryptic relatedness, all pairs of individuals displaying an identity-by-state (IBS) value larger than 1.6 were marked, and for each pair the individual with the lower typing rate was removed from the analysis. Cochran Armitage trend statistics were used to calculate significant association for autosomal SNPs. To visualize the outcome of the QC steps, Cochran Armitage p-values were depicted in a quantile-quantile plot (Figure 1). We observed good adherence of p-values to the line of expectance, which implies that potential spurious associations characterized by an inflation of highly significant p-values were successfully removed by our QC measures. The remaining slight deviations from the line of expectance are interpreted to include true genetic effects. Further correction for lambda42 improved the QQ-plot of Armitage p-values (eFigure1).
