Genome-wide DNA methylation analysis in families with multiple individuals diagnosed with schizophrenia and intellectual disability

Abstract

Objectives

Schizophrenia (SZ) and intellectual disability (ID) are both included in the continuum of neurodevelopmental disorders (NDDs). DNA methylation is known to be important in the occurrence of NDDs. The family study is conducive to eliminate the effects of relative epigenetic backgrounds, and to screen for differentially methylated positions (DMPs) and regions (DMRs) that are truly associated with NDDs.

Methods

Four monozygotic twin families were recruited, and both twin individuals suffered from NDDs (either SZ, ID, or SZ plus ID). Genome-wide methylation analysis was performed in all samples and each family. DMPs and DMRs between NDD patients and unaffected individuals were identified. Functional and pathway enrichment analyses were performed on the annotated genes.

Results

Two significant DMPs annotated to CYP2E1 were found in all samples. In Family One, 1476 DMPs mapped to 880 genes, and 162 DMRs overlapping with 153 unique genes were recognised. Our results suggested that the altered methylation levels of FYN, STAT3, RAC1, and NR4A2 were associated with the development of SZ and ID. Neurodevelopment and the immune system may participate in the occurrence of SZ and ID.

Conclusions

Our findings suggested that DNA methylation participated in the development of NDDs by affecting neurodevelopment and the immune system.

Keywords:

• Schizophrenia
• intellectual disability
• family study
• DNA methylation
• neurodevelopmental disorder

Acknowledgements

We would like to thank the patients and all the family members participating in this study.

Statement of interest

There are no conflicts of interest.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (NSFC-32070589 and NSFC-82171500) and the National Key Research and Development Program of China (2016YFC1306802 and 2016YFC1306800).