A hypothesis-driven pathway analysis reveals myelin-related pathways that contribute to the risk of schizophrenia and bipolar disorder.
Schizophrenia (SZ) and bipolar disorder (BD) are both severe neuropsychiatric disorders with a strong and potential overlapping genetic background. Multiple lines of evidence, including genetic studies, gene expression studies and neuroimaging studies, have suggested that both disorders are closely related to myelin and oligodendrocyte dysfunctions. In the current study, we hypothesized that the holistic effect of the myelin-related pathway contributes to the genetic susceptibility to both SZ and BD. We extracted pathway data from the canonical pathway database, Gene Ontology (GO), and selected a 'compiled' pathway based on previous literature. We then performed hypothesis-driven pathway analysis on GWAS data from the Psychiatric Genomics Consortium (PGC). As a result, we identified three myelin-related pathways with a joint effect significantly associated with both disorders: 'Myelin sheath' pathway (P(SZ) = 2.45E-7, P(BD) = 1.22E-3), 'Myelination' pathway (P(SZ) = 2.10E-4, P(BD) = 2.53E-24), and 'Compiled' pathway (P(SZ) = 4.57E-8, P(BD) = 2.61E-9). In comparing the SNPs and genes in these three pathways across the two diseases, we identified a substantial overlap in nominally associated SNPs and genes, which could be susceptibility SNPs and genes for both disorders. From these observations, we propose that myelin-related pathways may be involved in the etiologies of both SZ and BD.
Institute of Mental Health, Peking University, 51 Hua Yuan Bei Road, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, China.
Hao
H
Yu
Academy of Mathematics and Systems Science, Chinese Academy Of Sciences, Beijing, China.
Wenjian
W
Bi
Peking-Tsinghua Center for Life Sciences, Beijing 100871, China.
Chenxing
C
Liu
Academy of Mathematics and Systems Science, Chinese Academy Of Sciences, Beijing, China.
Yanlong
Y
Zhao
Institute of Mental Health, Peking University, 51 Hua Yuan Bei Road, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, China; Peking-Tsinghua Center for Life Sciences, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
Dai
D
Zhang
Institute of Mental Health, Peking University, 51 Hua Yuan Bei Road, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, China. Electronic address: dryue@bjmu.edu.cn.
Weihua
W
Yue
D001714:Bipolar Disorder / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009185:Myelin Proteins / Q000235:genetics*; D009186:Myelin Sheath / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D059467:Transcriptome
D009185:Myelin Proteins
Bipolar disorder; Genome-wide association study; Myelin; Pathway-based analysis; Schizophrenia