For the CoLaus cohort, raw genotyping data were normalized using the aroma.affymetrix framework32. Normalization steps included allelic cross-talk calibration33,34, intensity summarization using robust median average and correction for any PCR amplification bias. CN ratios for a given sample, at a given SNP or CN probe, were computed as the log2 ratio of the normalized intensity of this probe divided by the median across all the samples. CN ratios were subsequently smoothed by fitting a Loess function31. CNV calling was done using a new method based on a Gaussian mixture model (Valsesia et al., manuscript in preparation). This Gaussian mixture model fits four components (deletion, copy neutral, 1 and 2 additional copy) to CN ratios. The final copy number at each probe location is determined as the expected (dosage) copy number. The method has been validated by comparing test datasets with results from the CNAT35 and CBS36,37 algorithms and by replicating a subset of CoLaus subject on Illumina arrays. All calls at the 16p11.2 locus made by the highly stringent CBS algorithm were replicated by the Gaussian mixture model. Principal components
