Shared genetic liability between major depressive disorder and osteoarthritis

Bone & Joint Research

article

Fuquan Zhang¹  Shuquan Rao²  Ancha Baranova³ 

[1] Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University;State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College;School of Systems Biology, George Mason University

关键词: ESR1;    Mendelian randomization;    SOX5;    GPX1;    major depressive disorder;    Osteoarthritis (OA);    oestrogen;    genetic variations;    depressive symptoms;    single nucleotide polymorphism (SNP);    Protein-coding genes;    medical comorbidities;    brain;    osteoporosis;   

DOI  :  10.1302/2046-3758.111.BJR-2021-0277.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsDeciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations.MethodsLinkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases.ResultsMDD has a significant genetic correlation with OA (rg = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (bxy = 0.24) and genetic liability to OA conferred a causal effect on MDD (bxy = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 (ESR1), SRY-Box Transcription Factor 5 (SOX5), and Glutathione Peroxidase 1 (GPX1) may have therapeutic implications for both MDD and OA.ConclusionThe study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA.

【 授权许可】

CC BY-NC