Genome-wide association study implicates the role of TBXAS1 in the pathogenesis of depressive symptoms among the Korean population.

Autor: Park K; Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea., Do AR; Interdisciplinary Program of Bioinformatics, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea., Chung Y; Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea., Kim MJ; Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea., Rhee SJ; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea., Yoon DH; Department of Psychiatry, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea., Choi SH; Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea., Cho SJ; Department of Psychiatry, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.; Workplace Mental Health Institute, Kangbuk Samsung Hospital, Seoul, Republic of Korea., Kim HN; Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea. hanna147942@gmail.com.; Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea. hanna147942@gmail.com., Ahn YM; Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea. aym@snu.ac.kr.; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea. aym@snu.ac.kr.; Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea. aym@snu.ac.kr., Won S; Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea. won1@snu.ac.kr.; Interdisciplinary Program of Bioinformatics, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea. won1@snu.ac.kr.; Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea. won1@snu.ac.kr.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2024 Feb 06; Vol. 14 (1), pp. 80. Date of Electronic Publication: 2024 Feb 06.
DOI: 10.1038/s41398-024-02777-3
Abstrakt: Although depression is an emerging disorder affecting many people worldwide, most genetic studies have been performed in European descent populations. Herein, a genome-wide association study (GWAS) was conducted in Korean population to elucidate the genomic loci associated with depressive symptoms. Two independent cohorts were used as discovery datasets, which consisted of 6474 (1484 cases and 4990 controls) and 1654 (557 cases and 1097 controls) Korean participants, respectively. The participants were divided into case and control groups based on the Beck Depression Inventory (BDI). Meta-analysis using the two cohorts revealed that rs6945590 was significantly associated with the risk of depressive symptoms [P = 2.83 × 10 -8 ; odds ratio (OR) = 1.23; 95% confidence interval (CI): 1.15-1.33]. This association was validated in other independent cohorts which were another Korean cohort (258 cases and 1757 controls) and the East Asian study of the Psychiatric Genomics Consortium (PGC) (12,455 cases and 85,548 controls). The predicted expression levels of thromboxane A synthase 1 gene (TBXAS1), which encodes the enzyme thromboxane A synthase 1 and participates in the arachidonic acid (AA) cascade, was significantly decreased in the whole blood tissues of the participants with depressive symptoms. Furthermore, Mendelian randomization (MR) analysis showed a causal association between TBXAS1 expression and the risk of depressive symptoms. In conclusion, as the number of risk alleles (A) of rs6945590 increased, TBXAS1 expression decreased, which subsequently caused an increase in the risk of depressive symptoms.
(© 2024. The Author(s).)
Databáze: MEDLINE
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