A large-scale integrative analysis of GWAS and common meQTLs across whole life course identifies genes, pathways and tissue/cell types for three major psychiatric disorders

Yan Zhao; Xiao Liang; Feng Zhu; Yan Wen; Jiawen Xu; Jian Yang; Miao Ding; Bolun Cheng; Mei Ma; Lu Zhang; Shiqiang Cheng; Cuiyan Wu; Sen Wang; Xi Wang; Yujie Ning; Xiong Guo; Feng Zhang

doi:10.1016/j.neubiorev.2018.10.005

A large-scale integrative analysis of GWAS and common meQTLs across whole life course identifies genes, pathways and tissue/cell types for three major psychiatric disorders

Neurosci Biobehav Rev. 2018 Dec:95:347-352. doi: 10.1016/j.neubiorev.2018.10.005. Epub 2018 Oct 16.

Authors

Yan Zhao¹, Xiao Liang¹, Feng Zhu², Yan Wen¹, Jiawen Xu³, Jian Yang², Miao Ding¹, Bolun Cheng¹, Mei Ma¹, Lu Zhang¹, Shiqiang Cheng¹, Cuiyan Wu¹, Sen Wang¹, Xi Wang¹, Yujie Ning¹, Xiong Guo¹, Feng Zhang⁴

Affiliations

¹ School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China.
² Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
³ Health Science Center, Xi'an Jiaotong University, Xi'an, PR China.
⁴ School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China. Electronic address: fzhxjtu@mail.xjtu.edu.cn.

PMID: 30339835
DOI: 10.1016/j.neubiorev.2018.10.005

Abstract

Attention deficit hyperactivity disorder (ADHD), bipolar disorder (BP) and schizophrenia (SCZ) are complex psychiatric disorders. We conducted a large-scale integrative analysis of genome-wide association studies (GWAS) and life course consistent methylation quantitative trait loci (meQTLs) datasets. The GWAS data of ADHD (including 20,183 cases and 35,191 controls), BP (including 7481 cases and 9250 controls) and SCZ (including 36,989 cases and 113,075 controls) were derived from published GWAS. Life course consistent meQTLs dataset was obtained from a longitudinal meQTLs analysis of 1018 mother-child pairs. Gene prioritization, pathway and tissue/cell type enrichment analysis were conducted by DEPICT. We identified multiple genes and pathways with common or disease specific effects, such as NISCH (P = 9.87 × 10^-3 for BP and 2.49 × 10^-6 for SCZ), ST3GAL3 (P = 1.19 × 10^-2 for ADHD), and KEGG_MAPK_SIGNALING_PATHWAY (P = 1.56 × 10^-3 for ADHD, P = 4.71 × 10^-2 for BP, P = 4.60 × 10^-4 for SCZ). Our study provides novel clues for understanding the genetic mechanism of ADHD, BP and SCZ.

Keywords: Integrative analysis; Methylation quantitative trait loci; Psychiatric disorders.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review

MeSH terms

Attention Deficit Disorder with Hyperactivity / genetics*
Attention Deficit Disorder with Hyperactivity / metabolism
Bipolar Disorder / genetics*
Bipolar Disorder / metabolism
DNA Methylation
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Quantitative Trait Loci
Schizophrenia / genetics*
Schizophrenia / metabolism