Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 60,207 bioRxiv papers from 267,649 authors.

Integrating brain methylome with GWAS for psychiatric risk gene discovery

By Shizhong Han, Ying Lin, Minghui Wang, Fernando S. Goes, Kai Tan, Peter Zandi, Thomas Hyde, Daniel R Weinberger, James B. Potash, Joel E Kleinman, Andrew E Jaffe

Posted 11 Oct 2018
bioRxiv DOI: 10.1101/440206

DNA methylation (DNAm) is heritable and plays a role in brain development and function through transcriptional regulation. Aberrant DNAm in human brain has been linked to psychiatric disorders, potentially as mediators of common genetic risk variants. In this study, we hypothesize that common risk variants for psychiatric disorders may act through affecting DNAm level in human brain. We first aimed to investigate the heritability pattern of DNAm levels in the human prefrontal cortex. Secondly, through imputation-driven methylome-wide association study (MWAS), we aimed to identify CpG sites whose methylation levels are genetically associated and that show methylation-trait associations in the prefrontal cortex of patients with schizophrenia or bipolar disorder. Our heritability analysis showed that, of ~370,000 CpG sites measured with the Illumina HumanMethylation450 microarray, 17% were heritable (p < 0.05), with a mean heritability of 0.22. Heritable CpG sites were enriched in intergenic regions, CpG shore, and regulatory regions in prefrontal cortex. Our MWAS approach identified known and potentially novel risk genes harboring CpG sites of methylation-trait associations for schizophrenia or bipolar disorder, which were not detectable using three alternative strategies (blood-based methylome reference, transcriptome-wide association study, and two gene-based association tests). Gene set enrichment analysis for genes with methylation-trait association evidence revealed pathways clearly related to neuronal functions, but also highlighted additional biological mechanisms that may underlie psychiatric disorders, such as microRNA-related regulation. In conclusion, our results showed the power of integrating brain methylation data with GWAS for psychiatric risk gene discovery, with potential applications in brain-related disorders or traits.

Download data

  • Downloaded 310 times
  • Download rankings, all-time:
    • Site-wide: 30,578 out of 60,207
    • In bioinformatics: 3,962 out of 6,077
  • Year to date:
    • Site-wide: 24,256 out of 60,207
  • Since beginning of last month:
    • Site-wide: 24,193 out of 60,207

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News