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Chronobiol Med > Volume 1(1); 2019 > Article
Chronobiology in Medicine 2019;1(1):40-48.
DOI: https://doi.org/10.33069/cim.2018.0002    Published online March 15, 2019.
A Genome-Wide Association Study of Bipolar Disorder Using a Subphenotype: Sleeplessness Symptom of Bipolar Mania
Chul-Hyun Cho1  , Ji-Hye Choi2, Hyun Goo Woo2, Heon-Jeong Lee1 
1Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
2Department of Physiology, Ajou University School of Medicine, Suwon, Korea
Correspondence:  Heon-Jeong Lee, Tel: 82-2-920-5815, Fax: 82-2-929-7679, 
Email: leehjeong@korea.ac.kr
Received: 4 December 2018   • Revised: 21 January 2019   • Accepted: 21 January 2019
Abstract
Objective
Dividing bipolar disorder (BD) into clinical subphenotypes is a possible approach to determine the genetic basis of BD. The goal of this study was to find genes associated with BD by performing a genome-wide association study (GWAS) based on the subphenotypes, i.e., sleeplessness symptom of bipolar mania (SBM) vs. non-sleeplessness symptom of bipolar mania (NSBM).
Methods
A total of 2,191 cases, 1,434 controls, and 703,012 single nucleotide polymorphisms (SNPs) in the merged samples from the Translational Genomics Institute and the Genetic Association Information Network were investigated. In individuals with bipolar I disorder, a GWAS of SBM vs. NSBM was performed.
Results
We identified 44 trait-associated SNPs with p<10-4 in a case-only analysis. The most statistically significant peak p-value was observed for rs10492908 (odds ratio=0.1832; p=9.27×10-7; Permuted p=1.00×10-6), which is located within the region of the genome encoding WW domain-containing oxidoreductase (WWOX) on chromosome 16q23. A total of eight genomic regions of interest (ROIs) on chromosomes 3, 5, 8, 9, 12, and 17 were also identified, and ROR2 and ANKFN1 in two ROIs may be related with SBM.
Conclusion
Our results suggest several candidate genes and pathways that are related to SBM. In particular, WWOX, ROR2, and ANKFN1 are candidate genes related to SBM. Additional replication studies are needed to confirm these results.
Key Words: Bipolar disorder; Genome-wide association study; Sleeplessness
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