Psychiatry · 2 h ago
Study identifies genetic differences across three schizophrenia symptom subtypes
A study of 2,416 Chinese Han patients used symptom clustering to identify three schizophrenia subtypes, with the classification tested in a separate cohort of 480 patients. Subtype-specific genetic analyses found differences in associated loci and polygenic risk patterns, particularly for the subtype marked by prominent negative symptoms.
- Three symptom-defined schizophrenia subtypes were identified.
- The classification was tested in an independent cohort of 480.
- Most subtype-specific significant genes were linked to negative symptoms.
- Genetic findings do not yet guide treatment.
Researchers used K-means clustering of symptom profiles in 2,416 Chinese Han patients with schizophrenia to define clinical subtypes, then assessed the classification in an independent cohort of 480 patients. They identified three groups: low symptom severity (Cluster-L), severe symptoms (Cluster-S), and predominant negative symptoms (Cluster-N). The subtypes were also associated with different symptom-network structures.
Subtype-specific genome-wide association analyses detected three independent genome-wide significant loci. One locus in CNTN2 was associated with Cluster-N (lead SNP rs3767295; P=6.40×10⁻¹⁰; OR=0.62). Gene-based analyses identified eight significant risk genes, seven of them specific to Cluster-N. Polygenic risk patterns also differed: GABA-related and oligodendrocyte-progenitor-cell scores were elevated in Cluster-N, while astrocyte scores were elevated in Cluster-S; oligodendrocyte scores were elevated in both groups.
The findings suggest that symptom-based stratification may help identify genetic associations obscured by clinical heterogeneity. The study does not establish that these genetic patterns can guide diagnosis or treatment. Its results come from Chinese Han cohorts and require replication and assessment of clinical utility in other populations.
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BMC Medicine: Genetic architecture of schizophrenia clinical subtype ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.