Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia

• Published in: Genes, brain and behavior Vol. 16; no. 5; pp. 515 - 521
• Main Authors: Bruce, H. A., Kochunov, P., Paciga, S. A., Hyde, C. L., Chen, X., Xie, Z., Zhang, B., Xi, H. S., O'Donnell, P., Whelan, C., Schubert, C. R., Bellon, A., Ament, S. A., Shukla, D. K., Du, X., Rowland, L. M., O'Neill, H., Hong, L. E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2017; John Wiley & Sons, Inc
• Subjects: 3' Untranslated Regions; Action Potentials; Adult; Affective disorders; Anisotropy; Axons; Case-Control Studies; Central nervous system; Data processing; Diffusion tensor imaging; endophenotype; Female; fractional anisotropy; Functional anatomy; Genes; GWAS; Humans; imaging genetics; KCNQ1; KCNQ1 Potassium Channel - genetics; KCNQ1 protein; Male; Measuring techniques; Mental disorders; Middle Aged; Neuroimaging; Polymorphism, Single Nucleotide; Potassium; Potassium channels; Potassium channels (voltage-gated); Processing speed; psychiatric genetics; Psychology; Reaction Time; Schizophrenia; Schizophrenia - genetics; Schizophrenia - physiopathology; Signal transduction; Single-nucleotide polymorphism; Substantia alba; Temporal variations; Transcription; Transduction; white matter; White Matter - metabolism; White Matter - physiopathology; white matter; GWAS; psychiatric genetics; imaging genetics; KCNQ1; potassium channels; endophenotype; fractional anisotropy; Diffusion tensor imaging; processing speed
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/gbb.12372

Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons. We genotyped members of the large potassium channel gene family focusing on putatively functional single nucleotide polymorphisms (SNPs) in a population of 363 controls, 194 patients with schizophrenia spectrum disorder (SSD) and 28 patients with affective disorders with psychotic features who completed imaging and neuropsychological testing. We then performed three association analyses using three phenotypes – processing speed, whole‐brain white matter fractional anisotropy (FA) and schizophrenia spectrum diagnosis. We extracted SNPs showing an association at a nominal P value of <0.05 with all three phenotypes in the expected direction: decreased processing speed, decreased FA and increased risk of SSD. A single SNP, rs8234, in the 3′ untranslated region of voltage‐gated potassium channel subfamily Q member 1 (KCNQ1) was identified. Rs8234 has been shown to affect KCNQ1 expression levels, and KCNQ1 levels have been shown to affect neuronal action potentials. This exploratory analysis provides preliminary data suggesting that KCNQ1 may contribute to the shared risk for diminished processing speed, diminished white mater integrity and increased risk of schizophrenia. Potassium channel genes may impact white matter microstructures that regulate axonal electric signal transmission and influence processing speed deficits seen in schizophrenia. A single nucleotide polymorphism in potassium channel subfamily Q member 1 (KCNQ1) is jointly associated with processing speed and white matter deficits in schizophrenia.