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Compr Psychiatry. 2019 Jan;88:65-69. doi: 10.1016/j.comppsych.2018.11.006. Epub 2018 Nov 28.

Integrative analysis of genome-wide association study and chromosomal enhancer maps identified brain region related pathways associated with ADHD.

Author information

1
School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China.
2
School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China. Electronic address: fzhxjtu@mail.xjtu.edu.cn.
3
School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China. Electronic address: maxiancang@xjtu.edu.cn.

Abstract

Attention deficit/hyperactivity disorder (ADHD) is among the most common childhood onset psychiatric behavioral disorders, and the pathogenesis of ADHD is still unclear. Utilizing the latest genome wide association studies (GWAS) data and enhancer map, we explored the brain region related biological pathways associated with ADHD. The GWAS summary data of ADHD was driven from a published study, involving 20,183 ADHD cases and 35,191 healthy controls. The brain-related enhancer map was collected from ENCODE and Roadmap Epigenomics (ENCODE + Roadmap) including 489,581 enhancers. Firstly, the chromosomal enhancer maps of four brain regions were aligned with the ADHD GWAS summary data in order to obtain enhancer SNPs. Then the significant enhancers SNPs were subjected to the gene set enrichment analysis (GSEA) for identifying ADHD associated gene sets. A total of 866 pathways and 4 brain tissues were analyzed in this study. We detected several candidate genes for ADHD, such as AHI1, ALG2 and DNM1. We also detected several candidate biological pathways associated with ADHD, such as Reactome SEMA4D in semaphorin signaling and Reactome NCAM1 interactions. Our findings may provide a novel insight into the complex genetic mechanism of ADHD.

KEYWORDS:

Attention deficit/hyperactivity disorder; Brain region; Enhancer; GWAS

PMID:
30529763
DOI:
10.1016/j.comppsych.2018.11.006
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