Integrated exome-transcriptome analysis of a schizophrenia case with an exceptionally low polygenic risk score

In post-mortem schizophrenia case SZ07 with an exceptionally low schizophrenia polygenic risk score (below the first percentile), only an IZUMO4 splice-acceptor variant had direct RNA-level support.

• Why it matters: The work addresses how rare, larger-effect variants might be detected in individuals with very low common-variant burden, and how to connect genomic candidates to molecular effects in brain tissue.
• What they did: The study performed exome analysis using multiple variant-prediction tools to prioritize variants, then used RNA sequencing from three cortical regions to test RNA-level support.
• The result: Broader transcriptomic pathway analysis implicated innate immune processes, calcium signalling, synaptic biology, and axon remodelling, with results largely compatible with SZ07’s cerebrovascular disease history.

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