Profesor John McGrath
Queensland Brain Institute
University of Queensland

Title: "Is complement component 4 (C4) associated with risk of schizophrenia: new data from Danish biobank samples."


The complement system, including complement components 3 and 4 (C3, C4), traditionally has been linked to innate immunity. More recently, complement components have also been implicated in brain development and the risk of schizophrenia. Based on a large, population-based case-cohort study, we measured the blood concentrations of C3 and C4 in 68,768 neonates. A genome-wide association study (GWAS) for C4 protein concentration identified 36 independent loci, 30 of which were in or near the major histocompatibility complex on chromosome 6 (which includes the C4 gene), while 6 loci were found on 6 other chromosomes. A GWAS for C3 identified 15 independent loci, 7 of which were located in the C3 gene on chromosome 19, and 8 loci on 5 other chromosomes.

We found no consistent evidence linking measured neonatal C3 and C4 concentrations, imputed C4 haplotypes, or predicted C4 gene expression with schizophrenia (SCZ), bipolar disorder (BIP), depression (DEP), autism spectrum disorder, attention deficit hyperactivity disorder or anorexia nervosa diagnosed in later life.

We present evidence from Mendelian randomisation (MR) and Phenomewide Association Studies (PheWAS) that explored this hypothesis. While we found no evidence linking C3 or C4 with risk of mental disorders, there was convergent evidence linking C4 with risk of a range of autoimmune disorders (in particular SLE).

This presentation will outline the utility of linking Danish registers and neonatal dried blood spots.



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