Shared genetic liability between major depressive disorder and osteoarthritis

Abstract

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 (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. 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.

Causal associations of tea intake with COVID-19 infection and severity

“…To achieve this, genetic variants are utilized as instrumental variables ( 34 ). The MR framework has been widely used in recent studies to explore relationships between related phenotypes ( 35 – 39 ). This study used the MR approach to test whether habitual tea intake exerts any causal influences on contracting SARS-CoV-2 and severe outcomes of COVID-19.…”

Depression and anxiety are associated with an increased risk of infection, revision, and reoperation following total hip or knee arthroplasty

“…An awareness of the influence of these conditions on pain and physical wellbeing has increased among providers in recent years. [1][2][3] Mental and social health factors have been identified as potential contributors to persistent pain, dissatisfaction, and complication rates following total hip arthroplasty (THA) and total knee arthroplasty (TKA). [4][5][6][7][8] Previous investigations have suggested that up to 20% of patients are dissatisfied following primary TKA.…”

No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization

“…For example, an existing MR analysis demonstrated that high iron levels have a positive causality with gout but a negative causality with rheumatoid arthritis (RA) (17). In addition, the genetic causal association between major depressive disorder (MDD) and osteoarthritis (OA) has also been documented in a recent MR study (19). However, few studies have focused on the association between iron status and OP using MR analysis.…”