Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

ICAR: endoscopic skull‐base surgery

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Quantitative In Vivo HR-pQCT Imaging of 3D Wrist and Metacarpophalangeal Joint Space Width in Rheumatoid Arthritis

In this technique development study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was applied to non-invasively image and quantify 3D joint space morphology of the wrist and metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA). HR-pQCT imaging (82μm voxel-size) of the dominant hand was performed in patients with diagnosed rheumatoid arthritis (RA, N=16, age:52.6±12.8) and healthy controls (CTRL, N=7, age:50.1±15.0). An automated computer algorithm was developed to segment wrist and MCP joint spaces. The 3D distance transformation method was applied to spatially map joint space width, and summarized by the mean joint space width (JSW), minimal and maximal JSW (JSW.MIN, JSW.MAX), asymmetry (JSW.AS), and distribution (JSW.SD) – a measure of joint space heterogeneity. In vivo precision was determined for each measure by calculating the smallest detectable difference (SDD) and root mean square coefficient of variation (RMSCV%) of repeat scans. Qualitatively, HR-pQCT images and pseudo-color JSW maps showed global joint space narrowing, as well as regional and focal abnormalities in RA patients. In patients with radiographic JSN at an MCP, JSW.SD was two-fold greater versus CTRL (p<0.01), and JSW.MIN was more than two-fold lower (p<0.001). Similarly, JSW.SD was significantly greater in the wrist of RA patients versus CTRL (p<0.05). In vivo precision was highest for JSW (SDD: 100μm, RMSCV: 2.1%) while the SDD for JSW.MIN and JSW.SD were 370 and 110μm, respectively. This study suggests that in vivo quantification of 3D joint space morphology from HR-pQCT, could improve early detection of joint damage in rheumatological diseases