Single-nucleotide polymorphisms (SNPs) were genotyped using the Human OmniExpressExome-8 v1.0 Bead Chip (Illumina, Inc.) in DNA samples from 42 cases, and 67 controls. Sample and SNP quality control (QC) and SNP imputation are described in the Supplementary Materials . A total of 95 samples (33 clozapine-induced myocarditis cases, 62 clozapine-tolerant controls) and 587,647 SNPs passed QC. Phasing and imputation were performed using the Haplotype Reference Consortium (HRC) panel v1.1 2016 14 (link). Post-imputation SNP QC was performed (Supplementary Methods ) and a final set of 6,822,414 bi-allelic SNPs remained and were used for association analysis.
Analysis of genotype data was conducted using an additive logistic regression model in SNPTEST v2.5 adjusting for clinical variables reaching statistical significance (P < 0.05) and the first four principal components from a genetic relatedness matrix to account for population stratification. The conventional genome-wide association study (GWAS) threshold of P < 5 × 10−8 was regarded as genome-wide significant (Bonferroni-corrected for 1 million SNPs). Since this threshold is conservative for small sample sizes, SNPs with P < 1 × 10−5 were considered suggestive of genome-wide significance.
Analysis of genotype data was conducted using an additive logistic regression model in SNPTEST v2.5 adjusting for clinical variables reaching statistical significance (P < 0.05) and the first four principal components from a genetic relatedness matrix to account for population stratification. The conventional genome-wide association study (GWAS) threshold of P < 5 × 10−8 was regarded as genome-wide significant (Bonferroni-corrected for 1 million SNPs). Since this threshold is conservative for small sample sizes, SNPs with P < 1 × 10−5 were considered suggestive of genome-wide significance.