Risk Of Atopy Research Articles

Paternal adverse childhood experiences are associated with a low risk of atopy in the offspring.

Parental adverse childhood experiences (ACE) might affect the offspring health through intergenerational inheritance. The aim of this study was to investigate how paternal ACE associate with offspring sensitisation and allergic rhinitis (AR). The study included 590 Finnish father-child dyads from the FinnBrain Birth Cohort Study. Outcomes were offspring sensitisation against allergens and AR at age 5.5 years. Paternal ACE up to 18 years were assessed using the Trauma and Distress Scale (TADS) with the lowest quarter as the reference group. Of the children, 317 (54%) were males. Sensitisation occurred in 162/533 (30%) and AR in 122/590 (21%). Paternal TADS (median 17 points; interquartile range 11-27) was inversely associated with the risk of sensitisation. Children whose fathers scored the highest quarter had the lowest risk of sensitisation (adjusted odds ratio 0.42; 95% confidence interval 0.24-0.75), followed by those in the second highest quarter (0.58; 0.34-0.99). The association between the highest quarter and reduced risk of AR was similar. Paternal ACE were associated with a low risk of offspring sensitisation and AR, suggesting paternal childhood stress might influence immune responses in their offspring.

Low glycaemic index diet in pregnancy and child asthma: follow-up of the ROLO trial.

Epidemiological evidence suggests that a higher intake of sugar during pregnancy is associated with a higher risk of childhood asthma and atopy. However, randomised trial evidence supporting such a link is lacking. This study aimed to examine whether a low glycaemic index (GI) dietary intervention during pregnancy decreases the risk of childhood asthma and eczema. This is a secondary analysis of 514 children from the ROLO trial. Healthy women were randomised to receive an intervention of low GI dietary advice or routine care from early pregnancy. Mothers reported current doctor-diagnosed eczema in their children at 2 years (n 271) and current doctor-diagnosed asthma and eczema in their children at 5 (n 357) and 9-11 years (n 391) of age. Multivariable logistic regression models were used test the effect of the intervention on child outcomes overall and stratified by maternal education. There was a suggestion of a reduction in asthma at 5 years of age in children whose mothers received the low GI dietary intervention during pregnancy compared with usual care (adjusted OR 0·46 (95 % CI 0·19, 1·09); P = 0·08). In stratified adjusted analyses, the intervention was associated with a reduced risk of asthma at 5 years of age in children born to mothers with incomplete tertiary level education but not in those with complete tertiary level education (OR 0·14 (95 % CI 0·02, 0·69); P = 0·010 and OR 1·03 (95 % CI 0·34, 3·13); P = 0·94, respectively). A low GI diet in pregnancy may reduce the risk of developing asthma in childhood, particularly amongst children born to mothers with lower educational attainment.

Elevated circulating group-2 innate lymphoid cells expressing activation markers and correlated tryptase AB1 levels in active ascariasis

IntroductionAscaris lumbricoides infection is one of the most common soil-transmitted helminthiasis and IgE response to this helminth may increase the risk of asthma, bronchial hyperreactivity and atopy. There is not enough evidence showing the role of group-2 innate lymphoid cells (ILC2) in the pathogenesis of helminth infections in humans. Here, we aimed to investigate and characterize the influence of Ascaris lumbricoides infection on circulating ILCs in endemically exposed subjects.MethodsNon-infected (NI; n=16) and Ascaris-infected (AI; n=16) subjects from an endemic area were included. Two consecutive stool samples from each subject were examined by Kato-Katz to define parasite infection. Antibodies to the ABA-1 antigen of Ascaris and Ascaris extract were measured by ELISA. ILC subsets and their activation markers (CD25, CD69, thymic stromal lymphopoietin receptor (TSLPR) were evaluated in its PBMC by flow cytometry. Proximity extension assay (PEA) was performed to explore plasma proteins associated to infection.ResultsNo significant differences in the relative or absolute frequencies of total ILCs, ILC1, ILC2 and ILC3 cells were observed regarding the infection status. However, within AI group, IgE-sensitized subjects to ABA-1 had higher frequencies and counts of ILC2 (p<0.05). Frequencies of CD25+, CD69+ and TSLPR+ ILC2 were higher in AI compared to the NI (p<0.01). Additionally, egg burden was positively correlated with CD69+ ILC2 frequencies (r=0.67; p=0.005). Tryptase alpha/beta 1 (TPSAB1), GP6 and several plasma proteins associated with cell growth and granulocyte chemotaxis were highly expressed in the AI group (p<0.05). Interestingly, TPSAB1 levels were positively correlated with ILC2 expressing activation markers frequencies, egg burden and IgE levels against Ascaris.DiscussionAscaris infection is associated with increased expression of ILC2 activation markers and TPSAB1, which may contribute to the type-2 response.

Early-life exposure to residential greenness and risk of asthma in a U.S. bronchiolitis cohort.

Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) is linked to childhood asthma development. Despite a growing understanding of risk factors for developing post-bronchiolitis asthma, protective factors remain unclear. In this study, we aimed to investigate whether exposure to residential greenness between birth and bronchiolitis hospitalization is associated with asthma and atopic asthma development by age 6 years. We analyzed a US severe bronchiolitis cohort from hospitalization to age 6 years, investigating how the normalized difference vegetation index (NDVI) and chlorophyll index green (CI green), measured in small (100 m) and large (500 m) radiuses around homes, relate to asthma and atopic asthma by age 6 years. We also explored whether maternal antibiotic use, daycare attendance, and respiratory virus type during hospitalization act as effect modifiers. The study cohort included 861 infants, with 239 (28%) developing asthma by age 6 years-152 atopic, 17 nonatopic, and 70 unclassified. Early life residential exposure to high NDVI and CI green levels was associated with lower odds of asthma (ORAdj for NDVI within a 100 m radius, 0.18; 95% CI, 0.05-0.78; and ORAdj for CI green levels within a 100 m radius, 0.53; 95% CI, 0.31-0.90). Associations also were significant for the development of atopic asthma (ORAdj 0.16; 95% CI, 0.03-0.96; and ORAdj 0.46; 95% CI, 0.25-0.92; respectively). Results were similar for the 500 m radius exposures. No effect modification was noted. In a U.S. bronchiolitis cohort, exposure to residential greenness between birth and bronchiolitis hospitalization is linked to lower asthma and atopic asthma risk by age 6 years.

Development and Validation of a Prognostic Clinical Risk Score for Subsequent Atopic Dermatitis Risk.

Development and Validation of a Prognostic Clinical Risk Score for Subsequent Atopic Dermatitis Risk.

53712 Atopic dermatitis and Risk of Venous thromboembolism: A Systematic Review and Meta-analysis

53712 Atopic dermatitis and Risk of Venous thromboembolism: A Systematic Review and Meta-analysis

50835 Air Quality Index (AQI) and atopic dermatitis risk in Taiwan: A nationwide population-based cohort study

50835 Air Quality Index (AQI) and atopic dermatitis risk in Taiwan: A nationwide population-based cohort study

Serum leptin and adiponectin function as indicators of allergic sensitization in pediatric adenotonsillar hypertrophy.

Obesity is commonly linked to both adenotonsillar hypertrophy (ATH) and allergic disorders, in which the roles of adipokines are not fully illuminated. This study aims to investigate the levels of leptin and adiponectin and their associations with allergic sensitization in pediatric ATH. Serum levels of specific immunoglobulin E (IgE), leptin and adiponectin were quantified in 35 controls and 111 ATH children, in which 54 were non-atopic and 57 were atopic. Spearman's correlation analysis and polynomial linear trend test were conducted. The odds ratios and 95% confidence intervals were calculated by binary logistic regression after multivariable adjustment. The serum level of leptin and leptin/adiponectin (L/A) ratio was significantly increased in children with ATH. An increase in leptin level and L/A ratio and a decrease in adiponectin level were observed in atopic children compared with non-atopic children. Among ATH children, the level of adiponectin was negatively while L/A ratio was positively correlated with specific IgE. After multivariable adjustment, leptin was significantly associated with increased risk of atopy to D. pteronyssinus and D. farina, and adiponectin was significantly associated with decreased risk of atopy to willow and mugwort. Leptin was associated with higher odds while adiponectin was associated with lower odds of overall atopy. Besides, significant multiplicative interactions of obesity with leptin and adiponectin on atopy were observed respectively. Leptin and adiponectin were both associated with allergic sensitization and function differently in pediatric ATH. Mechanistic studies are needed to elucidate the involvement of adipokines in allergic sensitization of pediatric ATH.

Features of the parietal and cavity intestinal microbiota in infants born to mothers with bronchial asthma, depending on the mode of delivery

Introduction. Intestinal microbiota is a complex and unique system in its composition, performing a huge number of diverse functions in the body. Its formation begins in utero.Aim. To study the features of the parietal and cavity intestinal microbiota in children born to mothers suffering from moderate bronchial asthma, depending on the mode of delivery.Material and methods. A prospective longitudinal study was carried out, which included children from the first day of life to 12 months. A total of 68 children at high risk of atopy (HRA) from mothers with asthma were included, of whom 22 were born by cesarean section and 46 were born through the vaginal birth canal. Qualitative and quantitative analysis of GM was carried out by real-time PCR with group- and species-specific primers: in the examined children, the dynamics of 4 phylums including 31 microorganisms was assessed. The child’s feces and brush-biopsy were taken from the rectum at 7 control points of measurement.Results and discussion. The data obtained showed that the method of delivery has an impact on the formation of the intestinal microbiota: in children born by cesarean section, in the parietal microbiota, starting from the age of 1–2 months, and in the cavity microbiota – 3–4 months, representatives of phylum Firmicutes (Clostridium leptum gr m.). In children born through the vaginal birth canal, all the first 8 months of life in the cavity and parietal microbiota were dominated by representatives of phylum Bacteroidetes (Bacteroides spp., Prevotella spp.). Clostridium leptum can be a marker of an inflammatory process in the intestinal mucosa in children at high risk of atopy. The research conducted over the past few years has found that Clostridium leptum promotes the secretion of anti-inflammatory (IL-10 and IL-12) and inhibition of the production of pro-inflammatory (IL-8) cytokines, and also boosts the number of Treg cells.Conclusion. The mode of delivery in children with a high risk of atopy is an additional epigenetic factor that influences the nature of both the parietal and cerebrospinal microbiota.

The Role of Infant Gut Microbiota Modulation by Perinatal Maternal Probiotic Intervention in Atopic Eczema Risk Reduction

Introduction: Probiotics have shown potential in reducing the occurrence of atopic eczema in high-risk infants. We aimed here to assess whether the preventive effect of maternal probiotic administration stems from compositional changes in early gut microbiota. Methods: This study included 46 mother-infant pairs from an original randomized controlled trial assessing the impact of maternal probiotic intervention with either the combinations of Lacticaseibacillus rhamnosus LPR and Bifidobacterium longum BL999, or Lacticaseibacillus paracasei ST11 and Bifidobacterium longum BL999, or placebo beginning 2 months before expected delivery and ending 2 months after birth. All children were vaginally delivered, full term and breastfed. During the 2-year follow-up period, the children were clinically evaluated by physicians for atopic eczema, and their gut microbiota was profiled at 1 and 6 months of age by 16S rRNA gene sequencing using an Illumina sequencing platform. Results: Altogether, 19 of 46 children developed atopic eczema by the age of 2 years. At 1 and 6 months of age, gut microbial diversity was similar between children who developed atopic eczema and their healthy controls, but at the age of 6 months, children who developed atopic eczema manifested with significantly higher relative abundance of Clostridia. Probiotic intervention did not significantly influence microbial diversity, and the effects on microbial composition were not consistent with the changes associated with the development of atopic eczema. Conclusion: The reduction of the risk of atopic eczema achieved by perinatal maternal probiotic intervention does not seem to require substantial gut microbiota modulation.

Association of Atopic Dermatitis and Risk of Glaucoma Surgery: A Global Population-Based Study

Précis: Severe atopic dermatitis (AD) in patients with glaucoma heightens the risk of requiring surgical intervention, necessitating prompt specialist care and strict surveillance. Objective: The impact of AD on the prognosis of patients with glaucoma is rarely studied. This study aims to assess the risk of requiring glaucoma surgery among patients with glaucoma with and without AD. Materials and Methods: In this retrospective cohort analysis, we assessed patients with glaucoma initially diagnosed from December 5, 2003 to December 3, 2018 using the TriNetX database, dividing them into AD and non-AD cohorts. 1:1 propensity-score matching created balanced groups for baseline traits and comorbidities. We compared the cohorts’ risk and cumulative incidence of needing glaucoma surgery (minimally invasive glaucoma surgery, trabeculectomy, aqueous shunt, or transscleral cyclophotocoagulation). A subgroup analysis was also conducted for patients with severe AD. Results: Out of 528,469 patients with glaucoma, 2624 were in the AD group. Among the AD group, 584 had severe AD. The AD group showed a comparable risk of requiring surgery to the non-AD group (hazard ratio: 1.03; 95% CI: 0.72, 1.47). In contrast, the severe AD group demonstrated a significantly greater risk and cumulative incidence of surgery (hazard ratio: 2.80; 95% CI: 1.37, 5.73; log-rank P = 0.003) compared with the non-AD group. Conclusion: Patients with glaucoma with severe AD are significantly more likely to need surgical intervention, with AD severity being a correlating factor for increased risk.

Evaluation of atopic diseases in patients with allergic contact dermatitis.

Background: There is controversy on whether allergic contact dermatitis (ACD) is associated with atopy. Research on eczema and the risk of ACD is mixed, and there is sparse literature on other atopic conditions. Objective: Our study examined the prevalence of several atopic conditions, including allergic rhinitis, eczema, asthma, and food allergies in patients with ACD, and compared these to patients without ACD. Methods: We retrospectively reviewed adult patients ages ≥ 18 years with ACD (n = 162) with positive patch testing results and documented any history of atopy, including childhood eczema, asthma, allergic rhinitis, and immunoglobulin E-mediated food allergy. The prevalence of atopic conditions was compared between our ACD cohort and controls without ACD (n = 163) from our electronic medical records system (age and gender matched). Results: Among our patients with ACD, 53 (33%) had allergic rhinitis, 22 (14%) had childhood eczema, 32 (20%) had asthma, and 8 (5%) had food allergies. We observed that the odds of atopy overall (n = 76) in the ACD group compared with the control group were increased (odds ratio [OR] 1.88; p = 0.007). Allergic rhinitis was the highest risk factor (n = 53) with an OR of 12.64 (p < 0.001). Childhood eczema (n = 22) was also increased in the ACD group (OR 2.4; p = 0.026). The odds of asthma and food allergy in the ACD group were also increased; however, the difference was not statistically significant from the control group (OR 1.76 [p = 0.071] and OR 2.76 [p = 0.139], respectively). Conclusion: Patients with ACD had increased odds of eczema, allergic rhinitis, and atopic conditions overall. Asthma and food allergies were not found to have a statistically significant correlation. Larger studies that delve into atopic risk factors in ACD would be important to confirm these findings.

Reduced atopic march risk in pediatric atopic dermatitis patients prescribed dupilumab versus conventional immunomodulatory therapy: A population-based cohort study

Dupilumab effectively treats atopic dermatitis (AD); however, its role in halting the atopic march remains uncertain. To investigate dupilumab's effect on atopic march in pediatric AD patients versus conventional immunomodulators. This retrospective cohort study utilized data from the TriNetX US Collaborative Network (2011-2024). Pediatric AD patients (≤18years) were categorized into DUPI-cohort (newly prescribed dupilumab) or CONV-cohort (prescribed conventional immunomodulators without dupilumab). After 1:1 propensity-score matching, we analyzed atopic march progression, defined by the incident asthma or allergic rhinitis (AR). Cumulative incidence was plotted using Kaplan-Meier, with risk assessment via Cox regression. The study included 2192 patients in each cohort. The 3-year cumulative incidence of atopic march progression was lower in the DUPI-cohort than the CONV-cohort (20.09% vs 27.22%; P<.001). The DUPI-cohort demonstrated significant risk reduction in atopic march progression (hazard ratio [HR] 0.68, 95% CI 0.55-0.83), individual asthma (HR 0.60, 0.45-0.81), and individual AR (HR 0.69, 0.54-0.88). Younger patients on dupilumab exhibited a greater risk reduction for atopic march progression and individual asthma, contrasting with the opposite age-related pattern for individual AR. Observational study. Among pediatric AD patients, dupilumab was associated with reduced risk of atopic march progression compared with conventional therapies.

Low glycaemic index diet in pregnancy and child asthma and eczema: follow-up of the ROLO trial

Atopic diseases, including asthma and eczema, represent a substantial public health problem in children and adolescents globally; asthma is the commonest chronic disorder of childhood(1). Research suggests that the origins of childhood asthma lie in utero, and several components of the maternal diet during pregnancy have been investigated in relation to atopic outcomes in children. Epidemiological evidence suggests that a higher intake of sugar during pregnancy is associated with a higher risk of childhood asthma and atopy(2,3). However, randomised trial evidence supporting such a link is lacking.Aims 1.To examine whether a low glycaemic index (GI) dietary intervention during pregnancy decreases the risk of asthma and eczema in childhood.2.To assess observationally whether maternal intake of sugar during pregnancy is positively associated with asthma and eczema in childhood.This is a secondary analysis of children from the ROLO trial. Healthy women were randomised to receive an intervention of low GI dietary advice or routine antenatal care from early pregnancy. All women completed a 3-day food diary in each trimester of pregnancy. Estimates of maternal intake of sugar in each trimester were averaged to provide mean intakes during pregnancy. Mothers reported current doctor-diagnosed eczema in their children at 2-years of age (n=271), and current doctor-diagnosed asthma and eczema in their children at 5 (n=357) and 9-11 years (n=391) of age. Multivariable logistic regression models were used a) to test the effect of the intervention on child outcomes overall, and stratified by maternal education level (with, versus without, a complete tertiary level education), and b), in observational analyses, to analyse the relation between sugar and carbohydrate intake in pregnancy and child outcomes.There was weak evidence overall for a reduction in asthma at 5-years of age in children whose mothers received the low GI dietary intervention during pregnancy compared to usual care [adjusted odds ratio (OR) 0.43 (95% CI 0.18, 1.03); P=0.06]. However, in stratified analyses the intervention was associated with a marked reduction in risk of asthma at 5-years of age in children born to mothers with lower educational attainment [adjusted OR 0.16 (0.03, 0.85); P=0.032]. Intake of sugar during pregnancy was positively associated with the development of asthma at any time point in childhood [adjusted OR per quartile of mean sugar intake 1.40 (0.99, 1.97), P-trend=0.048] and at 5-years of age [adjusted OR per quartile 1.55 (1.00, 2.40), P-trend=0.046]. No associations with eczema outcomes were found.This novel study provides stronger evidence that higher sugar intake during pregnancy is associated with an increased risk of asthma among offspring. An intervention to reduce sugar intake in pregnancy may have potential as a primary prevention strategy, particularly amongst children born to mothers with lower educational attainment.

Neonatal skin health and associated dermatological conditions.

This review describes recent developments in neonatal skincare management and situates these findings within the preexisting literature on neonatal dermatology. The studies included in this review expand research methods evaluating skincare management to different contexts across the world. Several studies explore the roles of emollient therapy, disinfection, and skin-to-skin contact on improving neonates' long-term health outcomes. Recent findings also assess the impact of neonatal interventions on atopic dermatitis risk later in life as well as epidemiological and microbiome variables that may predict this risk. Additionally, updates on various dermatological conditions unique to neonates are discussed in further detail. Neonatal skincare management differs in notable ways from that of other age groups. The presentation of dermatologic diseases as well as the rare conditions that affect neonates make their clinical management unique. The recent literature on neonatal dermatology can help inform clinicians regarding important considerations in treating their neonatal population.

Effect of Bifidobacterium bifidum Supplementation in Newborns Born from Cesarean Section on Atopy, Respiratory Tract Infections, and Dyspeptic Syndromes: A Multicenter, Randomized, and Controlled Clinical Trial.

Cesarean section is considered a possible trigger of atopy and gut dysbiosis in newborns. Bifidobacteria, and specifically B. bifidum, are thought to play a central role in reducing the risk of atopy and in favoring gut eubiosis in children. Nonetheless, no trial has ever prospectively investigated the role played by this single bacterial species in preventing atopic manifestations in children born by cesarean section, and all the results published so far refer to mixtures of probiotics. We have therefore evaluated the impact of 6 months of supplementation with B. bifidum PRL2010 on the incidence, in the first year of life, of atopy, respiratory tract infections, and dyspeptic syndromes in 164 children born by cesarean (versus 249 untreated controls). The results of our multicenter, randomized, and controlled trial have shown that the probiotic supplementation significantly reduced the incidence of atopic dermatitis, upper and lower respiratory tract infections, and signs and symptoms of dyspeptic syndromes. Concerning the gut microbiota, B. bifidum supplementation significantly increased α-biodiversity and the relative values of the phyla Bacteroidota and Actinomycetota, of the genus Bacteroides, Bifidobacterium and of the species B. bifidum and reduced the relative content of Escherichia/Shigella and Haemophilus. A 6-month supplementation with B. bifidum in children born by cesarean section reduces the risk of gut dysbiosis and has a positive clinical impact that remains observable in the following 6 months of follow-up.

Helicobacter pylori Infection Does Not Protect Against Allergic Diseases: Evidence From a Pediatric Cohort From Northern Sardinia, Italy

ABSTRACTBackgroundThe “hygiene hypothesis” states that reduced exposure to microbial antigens due to an excessively hygienic environment can increase the risk of developing autoimmune diseases, including atopic disorders and asthma. In recent decades, there has been a progressive decline in the prevalence of numerous microorganisms following improved hygienic‐sanitary conditions. More specifically, several studies reported an inverse association between the reduction in Helicobacter pylori infection and the rise of asthma and allergic disorders.AimTo evaluate the prevalence of atopic disorders in a pediatric population in relation to seropositivity against H. pylori.MethodsChildren from Northern Sardinia, Italy, referred to the local Children's Hospital for any reason, were investigated to identify risk factors, especially H. pylori infection, associated with atopic disorders. A validated questionnaire, including demographics, house size, history of breastfeeding, residence, school or daycare center attendance, exposure to animals, and a defined diagnosis of atopy—including asthma—was filled out by a trained pediatrician according to parents' answers and child records. A blood sample was collected from each participant and immunoglobulin G against H. pylori was assessed by a locally validated ELISA test.ResultsThe seroprevalence of H. pylori infection was 11.7% among 492 children (240 females). Thirty‐two children had a confirmed diagnosis of asthma and 12 of allergy. No one child showed both conditions. Statistically significant differences in H. pylori seropositivity were not detected between children with or without atopy (8.4% vs. 12.6; p = 0.233). Although atopic disorders were more frequent in children exposed to traditional atopic risk factors, none of them showed to be significant after adjusting for all covariates.ConclusionsSerologically assessed H. pylori infection was not significantly associated with a reduced risk of atopic diseases in children.

Antibiotics taken within the first year of life are linked to infant gut microbiome disruption and elevated atopic dermatitis risk

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in both pediatric and adult populations. The development of AD has been linked to antibiotic usage, which causes perturbation of the microbiome and has been associated with abnormal immune system function. However, imbalances in the gut microbiome itself associated with antibiotic usage have been inconsistently linked to AD. This study aimed to elucidate the timing and specific factors mediating the relationship between systemic (oral or intravenous) antibiotic usage and AD. We used statistical modeling and differential analysis to link CHILD Cohort Study participants' history of antibiotic usage and early-life gut microbiome alterations to AD. Here we report that systemic antibiotics during the first year of life, as compared to later, are associated with AD risk (adjusted odds ratio [aOR]= 1.81; 95% CI: 1.28-2.57; P< .001), with an increased number of antibiotic courses corresponding to a dose response-like increased risk of AD risk (1 course: aOR: 1.67; 95% CI: 1.17-2.38; 2 or more courses: aOR: 2.16; 95% CI: 1.30-3.59). Further, we demonstrate that microbiome alterations associated with both AD and systemic antibiotic usage fully mediate the effect of antibiotic usage on the development of AD (βindirect= 0.072; P< .001). Alterations in the 1-year infant gut microbiome of participants who would later develop AD included increased Tyzzerella nexilis, increased monosaccharide utilization, and parallel decreased Bifidobacterium and Eubacterium spp, and fermentative pathways. These findings indicate that early-life antibiotic usage, especially in the first year of life, modulates key gut microbiome components that may be used as markers to predict and possibly prevent the development of AD.

Identifying Atopic Dermatitis Risk Loci in 1,094,060 Individuals with Subanalysis of Disease Severity and Onset

Atopic dermatitis (AD) is a common inflammatory skin disease highly attributable to genetic factors. In this study, we report results from a genome-wide meta-analysis of AD in 37,541 cases and 1,056,519 controls with data from the FinnGen project, the Estonian Biobank, the UK Biobank, the EAGLE Consortium, and the BioBank Japan. We detected 77 independent AD-associated loci, of which 10 were, to our knowledge, previously unreported. The associated loci showed enrichment in various immune regulatory processes. We further performed subgroup analyses of mild and severe AD and of early- and late-onset AD, with data from the FinnGen project. Fifty-five of the 79 tested variants in the associated loci showed larger effect estimates for severe than for mild AD as determined through administered treatment. The age of onset, as determined by the first hospital visit with AD diagnosis, was lower in patients with particular AD-risk alleles. Our findings add to the knowledge of the genetic background of AD and may underlie the development of new therapeutic strategies.

Causal role of vitamin E in atopic dermatitis risk: A Mendelian randomization study.

Prior studies suggested that vitamin E might be beneficial in alleviating atopic dermatitis, but confirming a causal link was hindered by limitations such as sample sizes and unaccounted confounders. The present study aimed to clarify this through Mendelian randomization (MR) analysis. GWAS summary statistics was obtained from public databases encompassing a study on vitamin E and two studies related to atopic dermatitis. Two sets of instrumental variables (IVs) were selected using lenient (p < 1e-5) and strict (p < 5e-6) thresholds for separate MR analyses. Inverse variance weighted (IVW) was used as the primary MR method, supplemented by six additional MR methods, and followed by a meta-analysis to consolidate the impact of vitamin E on atopic dermatitis from two independent studies. Furthermore, various sensitivity tests were performed to assess the reliability of the MR results. A meta-analysis of IVW analyses deriving from two different atopic dermatitis cohorts under lenient IV selection thresholds demonstrated that vitamin E exhibited a significant lowering risk of atopic dermatitis effect (OR = 0.817, 95% CI: 0.673-0.991, p = .041), which was validated under strict IV selection thresholds (OR = 0.822, 95% CI: 0.709-0.954, p = .010). In addition, six other MR methods remained parallel to IVW (OR > 1). Multiple sensitivity tests showed that MR analyses were not affected by heterogeneity and horizontal pleiotropy. Overall, this MR study supported vitamin E reducing the risk of atopic dermatitis. Consequently, maintaining an adequate intake of vitamin E could potentially serve as an effective preventive measure against atopic dermatitis.