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MAOA Variants and Genetic Susceptibility to Major Psychiatric Disorders

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Abstract

Monoamine oxidase A (MAOA) is a mitochondrial enzyme involved in the metabolism of several biological amines such as dopamine, norepinephrine, and serotonin, which are important neurochemicals in the pathogenesis of major psychiatric illnesses. MAOA is regarded as a functional plausible susceptibility gene for psychiatric disorders, whereas previous hypothesis-driven association studies obtained controversial results, a reflection of small sample size, genetic heterogeneity, or true negative associations. In addition, MAOA is not analyzed in most of genome-wide association studies (GWAS) on psychiatric disorders, since it is located on Chromosome Xp11.3. Therefore, the effects of MAOA variants on genetic predisposition to psychiatric disorders remain obscure. To fill this gap, we collected psychiatric phenotypic (schizophrenia, bipolar disorder, and major depressive disorder) and genetic data in up to 18,824 individuals from diverse ethnic groups. We employed classical fixed (or random) effects inverse variance weighted methods to calculate summary odds ratios (OR) and 95 % confidence intervals (CI). We identified a synonymous SNP rs1137070 showing significant associations with major depressive disorder (p = 0.00067, OR = 1.263 for T allele) and schizophrenia (p = 0.0039, OR = 1.225 for T allele) as well as a broad spectrum of psychiatric phenotype (p = 0.000066, OR = 1.218 for T allele) in both males and females. The effect size was similar between different ethnic populations and different gender groups. Collectively, we confirmed that MAOA is a risk gene for psychiatric disorders, and our results provide useful information toward a better understanding of genetic mechanism involving MAOA underlying risk of complex psychiatric disorders.

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Acknowledgments

This work was supported by the Key Disciplines (Ecology) Project of Yunnan Education Department and by grants from the Chinese National Natural Science Foundation (31360516). X.J.L was supported by the 100 Talents Program (BaiRenJiHua) of the Chinese Academy of Sciences.

Conflict of Interest

The authors declare no conflict of interest.

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    Authors and Affiliations

    1. Key Laboratory of Special Biological Resource Development and Utilization of Universities in Yunnan Province, Department of Biological Science and Technology, Kunming University, Kunming, Yunnan, People’s Republic of China

      Zichao Liu

    2. First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, People’s Republic of China

      Liang Huang

    3. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, People’s Republic of China

      Xiong-jian Luo & Ming Li

    4. School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, People’s Republic of China

      Lichuan Wu

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    Liu, Z., Huang, L., Luo, Xj. et al. MAOA Variants and Genetic Susceptibility to Major Psychiatric Disorders. Mol Neurobiol 53, 4319–4327 (2016). https://doi.org/10.1007/s12035-015-9374-0

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