The KCNH2 gene is associated with neurocognition and the risk of schizophrenia

Abstract

Objectives. A genetic variant (rs3800779; M30) in the KCNH2 gene has been associated with schizophrenia, a lower intelligence quotient (IQ) and processing speed scores, altered brain functions and increased KCNH2-3.1. mRNA levels in the hippocampus. The aims of this study were to investigate whether the KCNH2 polymorphism is associated with schizophrenia-related neurocognitive deficits and to confirm the association between the variant and schizophrenia. Methods. The effects of the risk genotype on IQ and seven neurocognitive batteries were examined by the analysis of covariance in 191 healthy subjects. We performed a meta-analysis of the association between M30 and schizophrenia using five independent ethnic groups (1,720 cases; 2,418 controls). Results. Consistent with the previous study, we provided evidence that subjects with the risk T carriers had significantly lower IQ scores than those with the G/G genotype (P = 0.048). Of the seven neurocognitive batteries, subjects with the risk genotype demonstrated lower performances on attention/vigilance (P = 0.0079) and working memory (P = 0.0066) relative to subjects with the G/G genotype. Meta-analysis demonstrated evidence for an association between M30 and schizophrenia without showing heterogeneity across studies (odds ratio = 1.18; P = 0.0017). Conclusions. These data suggest that the KCNH2 polymorphism could be associated with schizophrenia-related neuropsychological deficits and the risk of developing schizophrenia.

Key words::

• schizophrenia
• KCNH2 (potassium channel, voltage-gated subfamily H, member 2)
• intelligence quotient (IQ)
• single nucleotide polymorphism (SNP)
• meta-analysis
• neurocognition

Acknowledgments

We thank all individuals who participated in this study. We also appreciate Daniel R. Weinberger for critical comments on the manuscript. This work was supported in part by Grants-in-Aid from the Japanese Ministry of Health, Labor and Welfare (H18-kokoro-005, H19-kokoro-002, Comprehensive Research on Disability Health and Welfare, and the Research Committee of System Development for Clinical Trials in Psychiatry and Neurology), the Japanese Ministry of Education, Culture, Sports, Science and Technology (18689030), CREST of JST, and Japan Foundation for Neuroscience and Mental Health.

Statement of Interest

None to declare.