School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China.
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
Neurosci Biobehav Rev. 2018 Dec;95:347-352. doi: 10.1016/j.neubiorev.2018.10.005. Epub 2018 Oct 16.
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 for BP and 2.49 × 10 for SCZ), ST3GAL3 (P = 1.19 × 10 for ADHD), and KEGG_MAPK_SIGNALING_PATHWAY (P = 1.56 × 10 for ADHD, P = 4.71 × 10 for BP, P = 4.60 × 10 for SCZ). Our study provides novel clues for understanding the genetic mechanism of ADHD, BP and SCZ.
注意缺陷多动障碍（ADHD）、双相情感障碍（BP）和精神分裂症（SCZ）是复杂的精神疾病。我们对全基因组关联研究（GWAS）和全生命周期一致的甲基化定量性状基因座（meQTL）数据集进行了大规模综合分析。ADHD（包括 20183 例病例和 35191 例对照）、BP（包括 7481 例病例和 9250 例对照）和 SCZ（包括 36989 例病例和 113075 例对照）的 GWAS 数据来自已发表的 GWAS。全生命周期一致的 meQTL 数据集来自对 1018 对母婴进行的纵向 meQTL 分析。通过 DEPICT 进行基因优先级、途径和组织/细胞类型富集分析。我们确定了多个具有共同或疾病特异性效应的基因和途径，例如 NISCH（BP 的 P=9.87×10，SCZ 的 P=2.49×10）、ST3GAL3（ADHD 的 P=1.19×10）和 KEGG_MAPK_SIGNALING_PATHWAY（ADHD 的 P=1.56×10，BP 的 P=4.71×10，SCZ 的 P=4.60×10）。我们的研究为理解 ADHD、BP 和 SCZ 的遗传机制提供了新的线索。
