Chunk #13 — Results — eQTL at a common inversion polymorphism on chromosome 17q21 — Identification of gene expression changes in fetal brain associated with neuropsychiatric traits
Given evidence for a potential role of fetal brain eQTL in neuropsychiatric traits, we next applied summary data-based Mendelian randomization (SMR) to identify genetically influenced changes in gene expression in the fetal brain that could mediate genetic risk for these conditions. This approach employs Mendelian randomization to test for pleiotropic associations between gene expression and complex traits using eQTL and trait GWAS summary data [44, 45]. We tested for joint associations between gene expression and risk for the seven neuropsychiatric traits (attention deficit hyperactivity disorder, anorexia nervosa, autism spectrum disorder, bipolar disorder, major depressive disorder, neuroticism, and schizophrenia) using the same GWAS datasets as we used for enrichment analyses [26, 31–36]. We considered only eGenes and eTranscripts for which fetal brain eQTL were identified at FDR < 0.05, and report associations that survive correction for multiple tests (eGenes, P-SMR = 3.76 × 10− 5; eTranscripts, P-SMR < 1.54 × 10− 5). In addition, we only report associations that are non-significant (P > 0.05) for the HEIDI (heterogeneity in dependent instruments) test, indicating that they are unlikely to be driven by
