孟德尔随机化
全基因组关联研究
优势比
萧条(经济学)
医学
内科学
遗传关联
人口
生物信息学
遗传学
生物
基因型
基因
单核苷酸多态性
宏观经济学
环境卫生
遗传变异
经济
作者
Sungho Won,Kyungtaek Park,Ah Ra,Yuree Chung,Min Ji Kim,Sang Jin Rhee,Duk Yong Yoon,Seung Ho Choi,Sung‐Joon Cho,Hanna Kim,Yong Min Ahn
出处
期刊:Research Square - Research Square
日期:2022-11-28
标识
DOI:10.21203/rs.3.rs-2282327/v1
摘要
Abstract 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 6 474 (1 484 cases and 4 990 controls) and 1 654 (557 cases and 1 097 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 1 757 controls) and the East Asian study of the Psychiatric Genomics Consortium (PGC) (15 771 cases and 178 777 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.
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