Humancytosnp 12 beadchip

Karyotyping of peripheral blood lymphocytes was performed using standard methods. Genomic DNA of individuals from Families A-C was tested using Human CytoSNP-12 BeadChips (~300 K; Illumina, San Diego, CA, USA). Array data were analysed using GenomeStudio (Illumina) and QuantiSNP
[28 (link)]. FISH employed standard protocols and various combinations of probes listed in Table 
1. The study used genome build hg19.

DNA amplification, labeling, and hybridization were performed according to the manufacturer's protocol of the HumanCytoSNP-12 BeadChip (Illumina). Two hundred ng of genomic DNA was subjected to DNA amplification for each of the samples. After hybridization and washing, the array slides were scanned on an iScan system (Illumina). Log R ratios (LRR) and B allele frequencies (BAF) were calculated using GenomeStudio version 2010.1 and visualized using KaryoStudio Data Analysis Software version 1.0 (Illumina). LRR and BAF represented the normalized signal intensity and the normalized ratio of the quantity of the B allele to the total quantity of both A and B alleles, respectively. Detection of copy neutral loss of heterozygosity (CNLOH) and copy number alterations (gain and loss) was performed using CNVpartition V3.0.7.0 (Illumina) and R-GADA (R-genome alteration detection analysis) [11 (link)], respectively, with default parameters.

Genotyping, quality contol and genotype imputation of the Lifelines Deep cohort have been published elsewhere (17 (link)). Briefly, DNA was isolated and genotyped using both the HumanCytoSNP-12 BeadChip and the ImmunoChip platforms (Illumina, San Diego, CA, USA). First, SNP quality control was applied independently for both platforms, and next the genotypes generated from both platforms were merged into one dataset. After merging and quality control, genotypes were imputed using the GoNL reference panel (15 (link)). For this study, we used 63 Candida-stimulated PBMC samples from which we measured proteins from the supernatant using OLINK proteomics as described below. Before QTL mapping, we performed QC per sample and SNP using the imputed genotypes as described for the 500FG cohort (Supplementary Figure 1). In total, we removed 11 outliers due to high relatedness, resulting in a total number of 52 samples for follow-up QTL mapping. Finally, we removed genetic variants with MAF < 5%, resulting in a total number of 5,464,689 variants that were used for pQTL mapping.

The procedures for genotyping, genetic data filtering and genotype imputation of the 500FG cohort had been previously described (6 (link)). Extracted DNA was genotyped using the commercially available SNP chip, Illumina HumanOmniExpressExome-8 v1.0. Following pre-imputation filtering steps for both markers and individuals, the remaining dataset SNP genotypes were imputed with GoNL as reference panel (16 ).
For Lifelines Deep cohort, genotyping and imputation was performed as previously described (17 ). Both the HumanCytoSNP-12 BeadChip and the ImmunoChip platforms (Illumina, San Diego, CA, USA) were used to genotype the isolated DNA. Independent markers quality control was performed for both platforms and subsequently merged into one dataset. After merging, genotype SNPs were imputed using IMPUTE2 (18 ) against the GoNL reference panel.