Stringent quality control was applied and only samples with individual call rate (> 0.98) and genotypes with high call rate (>0.98), no strong deviation from Hardy-Weinberg equilibrium (P >1x10−6 in controls or P >1x10−10 in cases) and low heterozygosity rates (∣ Fhet ∣ <0.2) were included. Genotypes were phased and imputed using the 1000 Genomes Project phase 3 (1KGP3)61,62 imputation reference panel and SHAPEIT63 and IMPUTE264. Relatedness and population stratification were evaluated using a set of high quality markers (genotyped autosomal markers with minor allele frequency (maf) >0.05, HWE P >1x10−4 and SNP call rate >0.98), which were pruned for linkage disequilibrium (LD) (r2 <0.075) resulting in a set of 37,425 pruned markers (markers located in long-range LD regions defined by Price et al.65 were excluded). Genetic relatedness was estimated using PLINK v1.966,67 to identify first and second-degree relatives (π^ >0.2) and one individual was excluded from each related pair (cases preferred kept over controls). Genetic outliers were identified for exclusion based on principal component analysis (PCA) using EIGENSOFT68,69. A genetic homogenous sample was defined based on a subsample of
