Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ2 meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico–replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has had a profound and prolonged impact on healthcare services and healthcare workers.AimsThe Australian COVID-19 Frontline Healthcare Workers Study aimed to investigate the severity and prevalence of mental health issues, as well as the social, workplace and financial disruptions experienced by Australian healthcare workers during the COVID-19 pandemic.MethodsA nationwide, voluntary, anonymous, single timepoint, online survey was conducted between 27 August and 23 October 2020. Individuals self-identifying as frontline healthcare workers in secondary or primary care were invited to participate. Participants were recruited through health organisations, professional associations or colleges, universities, government contacts and national media. Demographics, home and work situation, health and psychological well-being data were collected.ResultsA total of 9518 survey responses were received; of the 9518 participants, 7846 (82.4%) participants reported complete data. With regard to age, 4110 (52.4%) participants were younger than 40 years; 6344 (80.9%) participants were women. Participants were nurses (n=3088, 39.4%), doctors (n=2436, 31.1%), allied health staff (n=1314, 16.7%) or in other roles (n=523, 6.7%). In addition, 1250 (15.9%) participants worked in primary care. Objectively measured mental health symptoms were common: mild to severe anxiety (n=4694, 59.8%), moderate to severe burnout (n=5458, 70.9%) and mild to severe depression (n=4495, 57.3%). Participants were highly resilient (mean (SD)=3.2 (0.66)). Predictors for worse outcomes on all scales included female gender; younger age; pre-existing psychiatric condition; experiencing relationship problems; nursing, allied health or other roles; frontline area; being worried about being blamed by colleagues and working with patients with COVID-19.ConclusionsThe COVID-19 pandemic is associated with significant mental health symptoms in frontline healthcare workers. Crisis preparedness together with policies and practices addressing psychological well-being are needed.

BackgroundThe aetiology of juvenile idiopathic arthritis (JIA) is largely unknown. We have established a JIA biobank in Melbourne, Australia called CLARITY – ChiLdhood Arthritis Risk factor Identification sTudY, with the broad aim of identifying genomic and environmental disease risk factors. We present here study protocols, and a comparison of socio-demographic, pregnancy, birth and early life characteristics of cases and controls collected over the first 3 years of the study.MethodsCases are children aged ≤18 years with a diagnosis of JIA by 16 years. Controls are healthy children aged ≤18 years, born in the state of Victoria, undergoing a minor elective surgical procedure. Participant families provide clinical, epidemiological and environmental data via questionnaire, and a blood sample is collected.ResultsClinical characteristics of cases (n = 262) are similar to those previously reported. Demographically, cases were from families of higher socio-economic status. After taking this into account, the residual pregnancy and perinatal profiles of cases were similar to control children. No case-control differences in breastfeeding commencement or duration were detected, nor was there evidence of increased case exposure to tobacco smoke in utero. At interview, cases were less likely to be exposed to active parental smoking, but disease-related changes to parent behaviour may partly underlie this.ConclusionsWe show that, after taking into account socio-economic status, CLARITY cases and controls are well matched on basic epidemiological characteristics. CLARITY represents a new study platform with which to generate new knowledge as to the environmental and biological risk factors for JIA.