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Genotypic Association of the DAOA Gene with Resting-State Brain Activity in Major Depression

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Abstract

Compelling evidence suggests that the glutamatergic system may contribute to the pathophysiology of major depression (MDD). While the D-amino acid oxidase activator (DAOA) gene can affect glutamatergic function, its genetic associations with MDD and abnormal resting-state brain activity have yet to be elucidated. A total of 488 patients with MDD and 480 controls were recruited to examine MDD association for the DAOA gene in a Chinese population, of whom 53 medication-free patients and 46 well-matched controls underwent resting-state functional magnetic resonance imaging for regional homogeneity (ReHo) analysis. The differences in ReHo between genotypes of interest were initially tested by the Student’s t test, and the 2 × 2 (genotypes × disease status) ANOVA was then performed to identify the main effects of genotypes, disease status, and their interactions in MDD. Allelic association of the DAOA gene with MDD was observed for rs2391191, rs3918341, and rs778294 and haplotypic association for 2- and 3-SNP haplotypes. Six clusters in the cerebellum, right middle frontal gyrus and left middle temporal gyrus showed genotypic association between altered ReHo and rs2391191. The main effects of rs2391191 genotypes were found in the right culmen and right middle frontal gyrus. The left uvula and left middle temporal gyrus showed a genotypes × disease status interaction. Our results suggest that the DAOA gene may confer genetic risk of MDD. Genotypic effect of rs2391191 and its interaction with disease status may contribute to the altered ReHo in patients with MDD. Glutamatergic modulation may play an important role in alteration of the resting-state brain activities.

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Acknowledgments

We sincerely thank all the subjects for their participation in this study. We also thank the Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China and Department of MRI, Shanxi Provincial People's Hospital, Taiyuan, China, for their help with recruitments of subjects and sample collection.

Financial Disclosure

The work was supported by the research grants from the National Basic Research Program of China (2010CB529603and 2012CB517902), the National Natural Science Foundation of China (30971001, 30971054, 31021091, and 81171290), the Beijing Natural Science Foundation (7102109) and the Fok Ying Tong Education Foundation (121024). The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. All the authors listed have read through the manuscript, approved for publication, and declared no conflict of interest. Jun Chen and Yong Xu had full access to all of the data in the study and took their responsibility for the integrity of the data and the accuracy of data analysis.

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  1. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, and Peking Union Medical College, Tsinghua University, No.5 Dong Dan San Tiao, Beijing, 100005, People’s Republic of China

    Jun Chen, Juan Zhang, Yan Shen & Qi Xu

  2. Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030002, People’s Republic of China

    Yong Xu, Zhifen Liu & Kerang Zhang

  3. Department of MRI, Shanxi Provincial People’s Hospital, Taiyuan, 030002, People’s Republic of China

    Cheng Xu

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  1. Jun Chen
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  2. Yong Xu
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  3. Juan Zhang
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  4. Zhifen Liu
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  5. Cheng Xu
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  6. Kerang Zhang
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  7. Yan Shen
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  8. Qi Xu
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Correspondence to Kerang Zhang or Qi Xu.

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Jun Chen and Yong Xu contributed equally to this study.

This work was performed at the National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College

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Chen, J., Xu, Y., Zhang, J. et al. Genotypic Association of the DAOA Gene with Resting-State Brain Activity in Major Depression. Mol Neurobiol 46, 361–373 (2012). https://doi.org/10.1007/s12035-012-8294-5

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