Genotyping
Genotype data were available for all samples with DNA-methylation data in the three cohorts. The LBC and BSGS samples were genotyped with the Illumina Human610-Quad v1.0 genotyping platform, and data were available on all participants with DNA-methylation data. After QC, genotyped data were imputed with 1000 Genomes Phase 1 version 328 and IMPUTE2.29,30 The LifeLines DEEP samples were genotyped with the HumanCytoSNP-12 BeadChip and the ImmunoChip,31 a customized Illumina Infinium array. The data were merged and subsequently imputed with GoNL26,32 and IMPUTE2.29,30 Details of QC in each cohort are described below.

LBC Genotyping QC
DNA samples from each individual were genotyped with the Illumina Human610-Quad BeadChip. Individuals were excluded on the basis of unresolved gender discrepancy, relatedness, call rate (≤0.95), and evidence of non-European descent. SNPs were included in the analyses if they met the following conditions: call rate ≥ 0.98, minor allele frequency ≥ 0.01, and Hardy-Weinberg equilibrium test with p ≥ 0.001.

LifeLines DEEP Genotyping QC
Details of DNA extraction, genotyping, and QC are provided elsewhere.19

BSGS Genotyping QC
DNA samples from each individual were genotyped by the Scientific Services Division at deCODE Genetics (Iceland) with the Illumina Human610-Quad BeadChip. Genotypes were called with the Illumina BeadStudio software. A detailed description of genotyping QC can be found elsewhere.20,33