Common variants in the MKL1 gene confer risk of schizophrenia

Xiong Jian Luo, Liang Huang, Edwin J. Van Den Oord, Karolina A. Aberg, Lin Gan, Zhongming Zhao, Yong Gang Yao

Research output: Contribution to journalArticle

Abstract

Genome-wide association studies (GWAS) of schizophrenia have identified multiple risk variants with robust association signals for schizophrenia. However, these variants could explain only a small proportion of schizophrenia heritability. Furthermore, the effect size of these risk variants is relatively small (eg, most of them had an OR less than 1.2), suggesting that additional risk variants may be detected when increasing sample size in analysis. Here, we report the identification of a genome-wide significant schizophrenia risk locus at 22q13.1 by combining 2 large-scale schizophrenia cohort studies. Our meta-analysis revealed that 7 single nucleotide polymorphism (SNPs) on chromosome 22q13.1 reached the genome-wide significance level (P < 5.0 × 10-8) in the combined samples (a total of 38 441 individuals). Among them, SNP rs6001946 had the most significant association with schizophrenia (P = 2.04 × 10-8). Interestingly, all 7 SNPs are in high linkage disequilibrium and located in the MKL1 gene. Expression analysis showed that MKL1 is highly expressed in human and mouse brains. We further investigated functional links between MKL1 and proteins encoded by other schizophrenia susceptibility genes in the whole human protein interaction network. We found that MKL1 physically interacts with GSK3B, a protein encoded by a well-characterized schizophrenia susceptibility gene. Collectively, our results revealed that genetic variants in MKL1 might confer risk to schizophrenia. Further investigation of the roles of MKL1 in the pathogenesis of schizophrenia is warranted.

Original languageEnglish (US)
Pages (from-to)715-727
Number of pages13
JournalSchizophrenia Bulletin
Volume41
Issue number3
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Schizophrenia
Genes
Single Nucleotide Polymorphism
Genome
Protein Interaction Maps
Genome-Wide Association Study
Linkage Disequilibrium
Sample Size
Meta-Analysis
Cohort Studies
Chromosomes
Brain

Keywords

  • Genetic association
  • GSK3B
  • MKL1
  • Protein-protein interaction
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Luo, X. J., Huang, L., Van Den Oord, E. J., Aberg, K. A., Gan, L., Zhao, Z., & Yao, Y. G. (2015). Common variants in the MKL1 gene confer risk of schizophrenia. Schizophrenia Bulletin, 41(3), 715-727. https://doi.org/10.1093/schbul/sbu156

Common variants in the MKL1 gene confer risk of schizophrenia. / Luo, Xiong Jian; Huang, Liang; Van Den Oord, Edwin J.; Aberg, Karolina A.; Gan, Lin; Zhao, Zhongming; Yao, Yong Gang.

In: Schizophrenia Bulletin, Vol. 41, No. 3, 01.01.2015, p. 715-727.

Research output: Contribution to journalArticle

Luo, XJ, Huang, L, Van Den Oord, EJ, Aberg, KA, Gan, L, Zhao, Z & Yao, YG 2015, 'Common variants in the MKL1 gene confer risk of schizophrenia', Schizophrenia Bulletin, vol. 41, no. 3, pp. 715-727. https://doi.org/10.1093/schbul/sbu156
Luo XJ, Huang L, Van Den Oord EJ, Aberg KA, Gan L, Zhao Z et al. Common variants in the MKL1 gene confer risk of schizophrenia. Schizophrenia Bulletin. 2015 Jan 1;41(3):715-727. https://doi.org/10.1093/schbul/sbu156
Luo, Xiong Jian ; Huang, Liang ; Van Den Oord, Edwin J. ; Aberg, Karolina A. ; Gan, Lin ; Zhao, Zhongming ; Yao, Yong Gang. / Common variants in the MKL1 gene confer risk of schizophrenia. In: Schizophrenia Bulletin. 2015 ; Vol. 41, No. 3. pp. 715-727.
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