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Updated: Aug 7, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
A significant, functional and replicable risk KTN1 variant block for schizophrenia
Qiao Mao1, Xiandong Lin2, Qin Yin3
1Department of Psychosomatic Medicine, People's Hospital of Deyang City, Deyang, 618000, Sichuan, China.
Genetic variants in the kinectin 1 gene (KTN1) are linked to schizophrenia risk. These variants influence KTN1 expression, brain structure, and intracranial volume, suggesting a role in schizophrenia pathogenesis.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Schizophrenia is associated with structural brain alterations, including enlarged basal ganglia gray matter volumes (GMVs).
- Genome-wide association studies identified the kinectin 1 gene (KTN1) as a key regulator of putamen GMV.
Purpose of the Study:
- To investigate the role of KTN1 variants in schizophrenia risk and pathogenesis.
- To analyze the association between KTN1 single nucleotide polymorphisms (SNPs) and schizophrenia in diverse populations.
Main Methods:
- Analyzed 849 SNPs across the KTN1 gene in large European, African-American, and mixed ancestry cohorts (totaling over 63,000 individuals).
- Examined the regulatory effects of schizophrenia-associated variants on KTN1 mRNA expression, intracranial volume (ICV), subcortical GMVs, and cortical surface area (SA) and thickness (TH).
Main Results:
- Identified a block of 26 KTN1 SNPs associated with schizophrenia risk across multiple samples.
- Schizophrenia-risk alleles (minor alleles) consistently increased KTN1 mRNA expression, ICV, and some cortical SA/TH.
- Conversely, these alleles significantly decreased basal ganglia GMVs, particularly the putamen, and some regional cortical SA/TH.
Conclusions:
- A significant, functional block of KTN1 variants plays a critical role in schizophrenia risk and pathogenesis.
- KTN1 variants influence brain structure and gene expression, providing a potential mechanism for their association with schizophrenia.
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