Association between NT5C2 rs11191580 and autism spectrum disorder in the Chinese Han population

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Introduction

Autism spectrum disorders (ASD) are a range of neurodevelopmental disability characterized by deficits in social communication and social interaction, as well as the repetitive behavior, interests, or activities. The analysis of genome-wide SNP data in European population found that rs11191580 was associated with the combination of five traits, including schizophrenia, ASD, bipolar disorder, major depressive disorder and attention deficit-hyperactivity disorder (Cross-Disorder Group of the Psychiatric Genomics, 2013). As the chromosome 10q24.32-33 is one of the most significant regions for schizophrenia, the replication studies of rs11191580 in independent population were mainly focused on schizophrenia (Guan et al., 2012; Li et al., 2017). Considering the genetic overlap between schizophrenia and ASD (King and Lord, 2011), it is compelling to investigate whether NT5C2 rs11191580 confers susceptibility to ASD. Only Wang replicated rs11191580 in 640 Chinese Han autism trios (Wang et al., 2019), which showed no association between rs11191580 and autism. To compensate for the non-randomness of the family study design, we performed this case-control study to explore the association between NT5C2 rs11191580 and ASD. To further understand the potential function of NT5C2 rs11191580, we conducted spatio-temporal expression pattern analysis of NT5C2 and investigated the effect of rs11191580 on NT5C2 expression from available public datasets.

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Methods

Our study included 602 ASD patients and 604 healthy controls in Chinese Han population. ASD patients were diagnosed by professional neurologists based on the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition. The control children were healthy population without neurodevelopmental disorders, and they were matched with ASD patients in gender. Genomic DNA was extracted from oral swabs or blood samples. Genotyping was performed with the SequenomMassARRAY platform.

We used the

Results

602 cases (520 boys and 82 girls, 5.39 ± 2.431 years) and 604 healthy controls (515 boys and 89 girls, 6.24 ± 1.930 years) were recruited. There was no statistically significant difference in the distribution of gender between groups (P = 0.579). The ratio of boys to girls between cases and controls was 6 to 1. Rs11191580 followed the Hardy-Weinberg equilibrium (P > 0.05). The statistical power for detecting the effects of rs11191580 was 91.3 %. The dominant model of rs11191580 in boys was

Discussion

We confirmed a nominal association of rs11191580 in NT5C2 with ASD in boys of Chinese under the dominant model. The NT5C2 was widely expressed in the brain subtissues and the expression of NT5C2 was fluctuated with brain development, indicating that NT5C2 may be involved in brain development (Yang et al., 2018a). We also found that the expression of NT5C2 gene was dysregulated in the ASD cases. Moreover, rs11191580 could regulate the expression of NT5C2 gene in several brain subtissues.

Financial disclosure

This work was supported by the National Natural Science Foundation of China to Ranran Song (grant number 81872636).

The funding source had no involvement in study design, the collection, analysis and interpretation of data, in the writing of the article and in the decision to submit the article for publication.

Author contributions

All authors contributed toward data analysis, drafting and revising the paper, gave final approval of the version to be published and agree to be accountable for all aspects of the work.

Declaration of Competing Interest

None.

Acknowledgments

The authors would like to thank all the study participants for being involved in the study.

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Ranran Song and Pengxiang Zuo should be considered joint senior author.

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