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Common SNPs and haplotypes in DGKH are associated with bipolar disorder and schizophrenia in the Chinese Han population

Molecular Psychiatry volume 16, pages 473–475 (2011)Cite this article

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Diacylglycerol kinase eta (DGKH) was the first bipolar disorder (BPD) susceptibility gene identified by genome-wide association study.1 It is located on 13q14, a region having shown some linkage evidence for BPD and schizophrenia (SCZ).2 DGKH encodes an important protein in the lithium-sensitive phosphatidyl inositol signaling pathway. A number of studies have been conducted in different European populations to replicate the association between DGKH and BPD. Although one study found positive haplotypic association in a Sardinian sample,3 all the others reported negative results.4, 5, 6 However, our preliminary meta-analysis (data not shown) indicated that the association of the three single-nucleotide polymorphisms (SNPs) (rs9315885, rs1012053 and rs1170191) found in all these studies, as well as in Welcome Trust Case Control Consortium (WTCCC) imputed data was all in the same direction. For further study of the possible role of DGKH in the pathogenesis of major psychiatric disorders and considering the genetic etiology overlap of BPD, SCZ and major depressive disorder, we carried out large-scale case–control studies to test the association between DGKH and these three disorders in the Chinese Han population.

Our sample sets consisted of 1139 unrelated BPD patients (645 type I BPD), 1122 unrelated SCZ patients, 1122 unrelated major depressive disorder patients and 1138 shared healthy controls. All subjects were of Chinese Han origin. Taqman assay was used to genotype 13 tag SNPs, including the three broadly replicated SNPs (rs9315885, rs1012053 and rs1170191). Main association analyses were performed on Haploview 4.1.7 Only haplotypes with an estimated frequency >3% were evaluated. 10 000 permutations were carried out to correct the multiple tests. The statistical power to detect a significant association at α⩽0.05 was above 85% in each single-site comparison and above 70% in the haplotype analyses, with a medium effect size (odds ratio (OR)=1.5). No severe deviations from Hardy–Weinberg equilibrium in controls were found.

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Acknowledgements

We warmly thank all patients and healthy individuals who participated in our study. This work was supported by Grants (2006AA02A407, 2009AA022701 and 2010CB529600), the Shanghai Changning Health Bureau program (2008406002) and the Shanghai Municipal Health Bureau program (2008095).

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Authors and Affiliations

  1. Bio-X Center and Affiliated Changning Mental Health Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China

    Z Zeng, T Wang, T Li, Y Li, P Chen, Q Zhao, J Liu, J Li, L He & Y Shi

  2. Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China

    Z Zeng, T Wang, T Li, Y Li, P Chen, Q Zhao, J Liu, J Li, L He & Y Shi

  3. Shanghai Institute of Mental Health, Shanghai, PR China

    G Feng

  4. Institutes of Biomedical Sciences, Fudan university, Shanghai, PR China

    L He

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  1. Z Zeng
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Correspondence to Y Shi.

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Zeng, Z., Wang, T., Li, T. et al. Common SNPs and haplotypes in DGKH are associated with bipolar disorder and schizophrenia in the Chinese Han population. Mol Psychiatry 16, 473–475 (2011). https://doi.org/10.1038/mp.2010.86

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