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J Affect Disord. 2015 Oct 1;185:149-55. doi: 10.1016/j.jad.2015.06.040. Epub 2015 Jun 25.

The GSK3B gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population.

Author information

1
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China; Shanghai Changning Mental Health Center, 299 Xiehe Road, Shanghai 200042, PR China.
2
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China.
3
College of Life Science, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, PR China.
4
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China.
5
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China; Shanghai Changning Mental Health Center, 299 Xiehe Road, Shanghai 200042, PR China; Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai 200042, PR China. Electronic address: shiyongyong@gmail.com.
6
Shanghai Changning Mental Health Center, 299 Xiehe Road, Shanghai 200042, PR China; Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai 200042, PR China. Electronic address: jidong1999@126.com.

Abstract

BACKGROUND:

Glycogen synthease kinase-3B is a key gene encoding a protein kinase which is abundant in brain, and is involved in signal transduction cascades of neuronal cell development and energy metabolism. Previous researches proposed GSK3B as a potential region for schizophrenia.

METHOD:

To validate the susceptibility of GSK3B to major depressive disorder, and to investigate the overlapping risk conferred by GSK3B for mental disorders, we performed a large-scale case-control study, analyzed 6 tag single nucleotide polymorphisms using TaqMan® technology in 1,045 major depressive disorder patients, 1,235 schizophrenia patients and 1,235 normal controls of Han Chinese origin.

RESULTS:

We found rs334535 (Pallele=2.79E-03, Pgenotype=5.00E-03, OR=1.429) and rs2199503 (Pallele=0.020, Pgenotype= 0.040, OR=1.157) showed association with major depressive disorder before Bonferroni correction. rs6771023 (adjusted Pallele=1.64E-03, adjusted Pgenotype=6.00E-03, OR=0.701) and rs2199503 (adjusted Pallele=0.001, adjusted Pgenotype=0.002, OR=1.251) showed significant association with schizophrenia after Bonferroni correction. rs2199503 (adjusted Pallele=1.70E-03, adjusted Pgenotype=0.006, OR=1.208) remained to be significant in the combined cases of major depressive disorder and schizophrenia after Bonferroni correction.

LIMITATIONS:

Further validations of our findings in samples with larger scale are suggested, and functional genomic study is needed to elucidate the role of GSK3B in signal pathway and psychiatric disorders.

CONCLUSIONS:

Our results provide evidence that the GSK3B gene could be a promising region which contains genetic risk for both major depressive disorder and schizophrenia in the Han Chinese population. The study on variants conferring overlapping risk for multiple psychiatric disorders could be tangible pathogenesis support and clinical or diagnostic references.

KEYWORDS:

Association Study; GSK3B gene; Major depressive disorder; Overlapping genetic risk factors; SNP; Schizophrenia

PMID:
26186530
DOI:
10.1016/j.jad.2015.06.040
[Indexed for MEDLINE]

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