Gene Discovery and Biological Insights into Anxiety Disorders from a Multi-Ancestry Genome-wide Association Study of >1.2 Million Participants.

We leveraged information from more than 1.2 million participants to investigate the genetics of anxiety disorders across five continental ancestral groups. Ancestry-specific and cross-ancestry genome-wide association studies identified 51 anxiety-associated loci, 39 of which are novel. Additionally, polygenic risk scores derived from individuals of European descent were associated with anxiety in African, Admixed-American, and East Asian groups. The heritability of anxiety was enriched for genes expressed in the limbic system, the cerebral cortex, the cerebellum, the metencephalon, the entorhinal cortex, and the brain stem. Transcriptome- and proteome-wide analyses highlighted 115 genes associated with anxiety through brain-specific and cross-tissue regulation. We also observed global and local genetic correlations with depression, schizophrenia, and bipolar disorder and putative causal relationships with several physical health conditions. Overall, this study expands the knowledge regarding the genetic risk and pathogenesis of anxiety disorders, highlighting the importance of investigating diverse populations and integrating multi-omics information.

All-Polyethylene Versus Metal-Backed Tibial Components in Total Knee Arthroplasty: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: In the literature, there is no evidence suggesting the superiority in clinical performance between all-polyethylene (AP) and metal-backed (MB) tibial implants in total knee arthroplasty. The aim of this study was to systematically review the literature to collect only high-quality studies investigating the differences in terms of clinical and radiostereometric analysis (RSA) outcomes of AP compared to MB implants. METHODS: Only randomized controlled trials (RCTs) reporting either clinical or RSA outcomes have been included. Data sources were Embase, Medline, and the Cochrane Central Register of Controlled Trials. RESULTS: We included eleven RCTs evaluating the outcomes of 1,377 patients. Of the RCTs, 9 of them showed a low risk and 2 showed moderate risk of bias. There was no statistically significant difference in terms of clinical outcomes and survival rate between the AP and MB group; however, a statistically significant lower mean lift-off in the AP group (0.19 mm) compared to the MB group (0.3 mm) was observed on RSA. CONCLUSIONS: The performance of AP total knee arthroplasty in terms of clinical outcomes and 5-year survival was not statistically different when compared to the MB group. However, the RSA showed a statistically significant lower mean lift-off in the AP group.