The following is the summary of “A genome-wide association study of chronic spontaneous urticaria risk and heterogeneity,” published in the May 2023 issue of Allergy & Clinical Immunology by Chang, et al.


Chronic spontaneous urticaria (CSU) is a skin disorder defined by spontaneous, itchy hives and/or angioedema that lasts for at least six weeks without any identifiable trigger. While some patients with CSU experience relief from their symptoms through antihistamines and second-line therapies such as omalizumab, others continue to experience symptoms that significantly impact their quality of life. In addition, the variable response to treatment and varying levels of autoantibodies observed in CSU patients emphasize the existence of clinically diverse subgroups within the patient population.

The objective was to shed light on the mechanisms underlying CSU by examining the genetics of CSU risk and its subgroups.

For a study, researchers conducted a genome-wide association analysis (GWAS) on 679 patients diagnosed with CSU and compared them to 4,446 control subjects. They also examined the genetic basis of chronic urticaria (CU) by analyzing the CU-index, which measures the levels of IgG autoantibodies, in a group of 447 CU-index low and 183 CU-index high patients. Additionally, they assessed whether polygenic scores for autoimmune-related disorders were associated with CSU risk and CU index.

The study yielded two loci that showed significant association with disease risk. The strongest association was detected at position 56 of HLA-DQA1 (P = 1.69 × 10−9), with the arginine residue found to be associated with an increased risk (odds ratio = 1.64). The second association signal co-localized with expression-quantitative trait loci for ITPKB in whole blood (Pcolocalization = .997). The arginine residue at position 56 of HLA-DQA1 was also associated with an increased risk of CU index–high (P = 6.15 × 10−5, odds ratio = 1.86), whereas the ITKPB association was not (P = .64). Additionally, the findings revealed that polygenic scores for three autoimmune-related disorders (hypothyroidism, type 1 diabetes, and vitiligo) were associated with both CSU risk and CU index (P < 2.34 × 10−3, odds ratio > 1.72).

From genome-wide association study (GWAS) of CSU identified two loci that were found to be significant on a genome-wide level. These findings underscore the shared genetic underpinnings of CSU and autoimmune disorders, as highlighted by the overlap between these loci and the genetics of CU index.

Reference – https://www.sciencedirect.com/science/article/pii/S0091674922014762