PMID- 35023758 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220223 IS - 2046-3758 (Print) IS - 2046-3758 (Electronic) IS - 2046-3758 (Linking) VI - 11 IP - 1 DP - 2022 Jan TI - Shared genetic liability between major depressive disorder and osteoarthritis. PG - 12-22 LID - 10.1302/2046-3758.111.BJR-2021-0277.R1 [doi] AB - AIMS: Deciphering 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. METHODS: Linkage 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. RESULTS: MDD has a significant genetic correlation with OA (r(g) = 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 (b(xy) = 0.24) and genetic liability to OA conferred a causal effect on MDD (b(xy) = 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. CONCLUSION: The 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. Cite this article: Bone Joint Res 2022;11(1):12-22. FAU - Zhang, Fuquan AU - Zhang F AUID- ORCID: 0000-0003-3204-8191 AD - Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. FAU - Rao, Shuquan AU - Rao S AD - State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. FAU - Baranova, Ancha AU - Baranova A AD - School of Systems Biology, George Mason University, Fairfax, Virginia, USA. AD - Research Centre for Medical Genetics, Moscow, Russia. LA - eng PT - Journal Article PL - England TA - Bone Joint Res JT - Bone & joint research JID - 101586057 PMC - PMC8801173 OTO - NOTNLM OT - ESR1 OT - GPX1 OT - Mendelian randomization OT - Osteoarthritis (OA) OT - Protein-coding genes OT - SOX5 OT - brain OT - depressive symptoms OT - genetic variations OT - major depressive disorder OT - medical comorbidities OT - oestrogen OT - osteoporosis OT - single nucleotide polymorphism (SNP) EDAT- 2022/01/14 06:00 MHDA- 2022/01/14 06:01 PMCR- 2022/01/13 CRDT- 2022/01/13 12:19 PHST- 2022/01/13 12:19 [entrez] PHST- 2022/01/14 06:00 [pubmed] PHST- 2022/01/14 06:01 [medline] PHST- 2022/01/13 00:00 [pmc-release] AID - BJR-11-12 [pii] AID - 10.1302/2046-3758.111.BJR-2021-0277.R1 [doi] PST - ppublish SO - Bone Joint Res. 2022 Jan;11(1):12-22. doi: 10.1302/2046-3758.111.BJR-2021-0277.R1.