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Chunk #63 — Methods — Statistical analyses — Analysis of the imputed genetically regulated gene expression

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Genome-wide association study implicates CHRNA2 in cannabis use disorder.
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The genetically regulated gene expression was imputed in 11 brain tissues using PrediXcan77 (models downloaded from: https://github.com/hakyimlab/PrediXcan; version 6 data). PrediXcan was used to impute the transcriptome for cases and the control group using SNP weights derived from models trained on reference transcriptome data sets including 10 brain tissues from GTEx78 (https://www.gtexportal.org/home/) and transcriptome data from dorsolateral prefrontal cortex generated by the CommonMind Consortium79,80. The models were trained on 1000 genome SNPs and contained only gene expression prediction models with a false discovery rate less than 5%. Gene expression levels in the iPSYCH data were imputed wave-wise and subseqeuntly the imputed data were merged. We tested for association of 2,459 – 10,930 protein coding genes (depending on the tissue; see Supplementary Table 6) with CUD using logistic regression. The analysis was based on the same individuals which were included in the GWAS (thus, genetic outliers and related individuals were removed) and corrected using genotyping wave and psychiatric disorders as covariates as well as the same principal components from PCA which were used in the GWAS . Since gene expression among