Humancoreexome 24 beadchip

Genomic DNA was obtained from saliva using Oragene OG‐500 saliva kits. Genotyping was performed using custom genotyping arrays (Illumina HumanCoreExome‐24 BeadChip) which contain 570,038 genetic variants (Illumina, Inc., San Diego, CA). Quality control was implemented in PLINK [Purcell et al., 2007], to ensure genotypes did not display ambiguous sex, cryptic relatedness up to third degree relatives by identity of descent, genotyping completeness <97%. We also removed non‐European ethnicity admixture detected as outliers in iterative EIGENSTRAT analyses of an LD‐pruned dataset [Price et al., 2006]. SNPs were excluded where the minor allele frequency was <1%, if the call rate <98% or if the χ²‐test for Hardy–Weinberg Equilibrium had a P‐value <1 e‐04. Individuals' genotypes were imputed using the pre‐phasing/imputation stepwise approach implemented in IMPUTE2/SHAPEIT with default parameters [Delaneau et al., 2012; Howie et al., 2009] and 1000 Genomes (December 2013, release 1000 Genomes haplotypes Phase I integrated variant set) as the reference dataset. Best guess genotypes were converted using gtool (http://www.well.ox.ac.uk/~cfreeman/software/gwas/gtool.html) and the default threshold of 0.8 was used.

Genomic DNA was isolated from whole blood of patients using standard procedures. Genotyping was performed for 1224 samples (500 cases and 724 controls) on the Illumina Human CoreExome-24 BeadChip (Illumina, Inc., San Diego, CA, USA) comprising 547,644 markers.

Blood samples of the control sample were genotyped by the Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (Cardiff, United Kingdom) using a custom ‘Illumina HumanCoreExome-24 BeadChip’ genotyping array, covering 570 038 genetic variants. As described elsewhere (Di Forti et al., 2019b ), the PRS-SZ were generated using PRSice from the summary results of the Psychiatric Genomics Consortium (PGC), wave 2 (Schizophrenia Working Group of the PGC, 2014 (link)). Clumping was performed to obtain SNPs in approximate linkage disequilibrium with an r² < 0.25 within a 250 kb window. PRS-SZ were calculated, at p-value thresholds of 0.05, because this threshold best captures liability to the disorder according to the PGC analysis (Schizophrenia Working Group of the PGC, 2014 (link)). The sample was restricted to 706 European descendant subjects (due to over-representation of European descendant subjects in the PGC2 training sample used to calculate the PRS-SZ).

Genomic DNA was obtained from saliva using Oragene OG‐500 saliva kits. Genotyping was performed using custom genotyping arrays (Illumina HumanCoreExome‐24 BeadChip), which contain 570 038 genetic variants (Illumina, Inc., San Diego, CA, USA). Quality control was implemented in plink (Purcell et al.2007) to ensure that the genotypes did not display ambiguous sex, cryptic relatedness (up to third‐degree relatives by the identity of descent), genotyping completeness <97% and non‐European ethnicity admixture (detected as outliers in iterative eigenstrat analyses of an LD‐pruned data set) (Price et al.2006). The SNPs were excluded where the minor allele frequency was <1%, if the call rate <98% or if the χ²‐test for Hardy–Weinberg Equilibrium had a P‐value <1 e‐04. Individuals' genotypes were imputed using the pre‐phasing/imputation stepwise approach implemented in impute2/shapeit (Delaneau et al.2012; Howie et al.2009) and 1000Genomes (December 2013, release 1000 Genome haplotypes Phase I integrated variant set) as the reference data set.

The NEO participants were genotyped on the Illumina HumanCoreExome-24 BeadChip (Illumina), at the Centre National de Génotypage (Evry Cedex, France). Following genotype QC steps, as previously described [38 ], sample were imputed to the Haplotype Reference Consortium release 1.1 [39 (link)], with further details in the study by Li-Gao et al. [29 (link)].

The general description of the NEO study is provided above. Genotyping was performed in participants form European ancestry, using the Illumina HumanCoreExome-24 BeadChip (Illumina Inc., San Diego, California, USA). Related individuals as well as individuals of a non-European ancestry were excluded for genotyping [38 (link)]. Subsequently, genotypes were imputed to the 1000 Genome Project reference panel (v3 2011). 4734 NEO participants were included in the GWAS that provided data for this study.