Assessment of a causal relationship between body mass index and atopic dermatitis.
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ABSTRACT:
SUBMITTER: Budu-Aggrey A
PROVIDER: S-EPMC7794861 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Assessment of a causal relationship between body mass index and atopic dermatitis.
Budu-Aggrey Ashley A Watkins Sarah H SH Brumpton Ben B Løset Mari M Tyrrell Jess J Modalsli Ellen H EH Vie Gunnhild Åberge GÅ Palmer Tom T Fritsche Lars G LG Nielsen Jonas Bille JB Romundstad Pål Richard PR Davey Smith George G Åsvold Bjørn Olav BO Paternoster Lavinia L Brown Sara J SJ
The Journal of allergy and clinical immunology 20200517 1
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Project description:Population studies suggest that atopic dermatitis (AD) is associated with an increased risk of obesity, however a causal relationship between these two conditions remains to be established. We therefore use Mendelian randomization (MR) to evaluate whether obesity and AD are causally interlinked. We used summary statistics extracted from genome wide association studies of Body Mass Index (BMI) and AD. MR analysis was performed in both directions to establish the direction of causality between BMI and AD. We find that genetically determined increase in adiposity is associated with increased risk of AD (odds ratio of AD 1.08 [95% CI 1.01 to 1.14; p = 0.015] per unit increase in BMI). Conversely, genetically determined increased risk of AD is not associated with a higher BMI (change in BMI attributable to AD based on genetic information: 0.00; 95% CI - 0.02 to 0.02; p = 0.862). There was no evidence for confounding of these genetic analyses by horizontal pleiotropy. Our results indicate that the association of AD with obesity is likely to reflect a causal role for adiposity in the development of AD. Our findings enhance understanding of the etiology of AD, and the basis for experimental studies to evaluate the mechanistic pathways by which adiposity promotes AD.
| S-EPMC7498603 | biostudies-literature
Project description:ImportanceAtopic dermatitis may be associated with short stature and obesity in children, but most previous studies have been either small or cross-sectional.ObjectiveTo evaluate the association between atopic dermatitis and height, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and weight throughout childhood.Design, setting, and participantsTARGet Kids! (The Applied Research Group for Kids) is an ongoing prospective longitudinal cohort study that collects data at routine physician visits throughout childhood. In this cohort, children aged 5 or younger were followed up into adolescence at regular physician visits at general pediatric and family practices in Toronto, Canada, from June 2008 to February 2021.ExposureParental report of atopic dermatitis.Main outcomes and measuresPrimary outcomes were length-for-age and BMI-for-age z scores. The secondary outcome was weight-for-age z score. Linear mixed effects models were used to estimate associations between atopic dermatitis and each outcome. In secondary analyses, interaction terms were included between atopic dermatitis and age.ResultsA total of 10 611 children were included in the analysis, with mean (SD) baseline age of 23 (20) months; 5070 (47.8%) participants were female. Participants were followed for a median (range) of 28.5 (0.0-158.0) months. A total of 1834 (17.3%) children had atopic dermatitis during follow-up. Atopic dermatitis was associated with lower length-for-age z score (-0.13; 95% CI, -0.17 to -0.09; P < .001), higher BMI z score (0.05; 95% CI, 0.01 to 0.09; P = .008), and lower weight-for-age z score (-0.07; 95% CI, -0.10 to -0.04; P < .001) compared with children without atopic dermatitis. The associations between atopic dermatitis and height and BMI changed with age, diminishing by age 14 years and 5.5 years, respectively. Based on World Health Organization growth tables, children with atopic dermatitis were on average 0.5 cm shorter with 0.2 more BMI units at age 2 years and 0.6 cm shorter with no difference in BMI at age 5 years than children without atopic dermatitis after adjusting for covariates. There was no evidence of interaction between atopic dermatitis and age with respect to weight.Conclusions and relevanceIn this cohort study, atopic dermatitis was associated with shorter stature, higher BMI, and lower weight in early childhood, but these associations were small and, for height and BMI, attenuated with age and resolved by adolescence.
| S-EPMC8600455 | biostudies-literature
Project description:ObjectiveThe study aimed to explore the causal effect of body mass index (BMI) on osteoarthritis.MethodsThe genome-wide association data of BMI and osteoarthritis were obtained via the Mendelian randomization (MR)-base platform. Single nucleotide polymorphisms (SNPs) significantly associated with BMI were identified and used as instrumental variables, and the causal relationship between BMI and osteoarthritis was examined using the two-sample MR research method. Three statistical methods including inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were employed.ResultsA total of 79 SNPs significantly associated with BMI were identified in the study (P<5×10-8; linkage disequilibrium r2 <0.1). Consistent association between BMI and osteoarthritis was observed when evaluated by different methods (IVW: odds ratio (OR) 1.028, 95% confidence interval (CI) 1.021-1.036; weighted median estimator: OR 1.028, 95% CI 1.019-1.037; MR-Egger regression: OR 1.028, 95% CI 1.009-1.046), which suggests that BMI is positively associated with increased risk of osteoarthritis. There was no evidence that the observed causal effect between BMI and the risk of osteoarthritis was affected by genetic pleiotropy (MR-Egger intercept 1.3×10-5, P=0.959).ConclusionThe MR analysis provided the strong evidence to indicate that BMI might be causally associated with the risk of osteoarthritis.
| S-EPMC8180293 | biostudies-literature
Project description:BackgroundPsoriasis is a common inflammatory skin disease that has been reported to be associated with obesity. We aimed to investigate a possible causal relationship between body mass index (BMI) and psoriasis.Methods and findingsFollowing a review of published epidemiological evidence of the association between obesity and psoriasis, mendelian randomization (MR) was used to test for a causal relationship with BMI. We used a genetic instrument comprising 97 single-nucleotide polymorphisms (SNPs) associated with BMI as a proxy for BMI (expected to be much less confounded than measured BMI). One-sample MR was conducted using individual-level data (396,495 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (356,926 individuals) from published BMI and psoriasis genome-wide association studies (GWASs). The one-sample and two-sample MR estimates were meta-analysed using a fixed-effect model. To test for a potential reverse causal effect, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis were used to test whether genetic risk for this skin disease has a causal effect on BMI. Published observational data showed an association of higher BMI with psoriasis. A mean difference in BMI of 1.26 kg/m2 (95% CI 1.02-1.51) between psoriasis cases and controls was observed in adults, while a 1.55 kg/m2 mean difference (95% CI 1.13-1.98) was observed in children. The observational association was confirmed in UK Biobank and HUNT data sets. Overall, a 1 kg/m2 increase in BMI was associated with 4% higher odds of psoriasis (meta-analysis odds ratio [OR] = 1.04; 95% CI 1.03-1.04; P = 1.73 × 10(-60)). MR analyses provided evidence that higher BMI causally increases the odds of psoriasis (by 9% per 1 unit increase in BMI; OR = 1.09 (1.06-1.12) per 1 kg/m2; P = 4.67 × 10(-9)). In contrast, MR estimates gave little support to a possible causal effect of psoriasis genetic risk on BMI (0.004 kg/m2 change in BMI per doubling odds of psoriasis (-0.003 to 0.011). Limitations of our study include possible misreporting of psoriasis by patients, as well as potential misdiagnosis by clinicians. In addition, there is also limited ethnic variation in the cohorts studied.ConclusionsOur study, using genetic variants as instrumental variables for BMI, provides evidence that higher BMI leads to a higher risk of psoriasis. This supports the prioritization of therapies and lifestyle interventions aimed at controlling weight for the prevention or treatment of this common skin disease. Mechanistic studies are required to improve understanding of this relationship.
| S-EPMC6354959 | biostudies-literature
Project description: Not available
| S-EPMC10545112 | biostudies-literature
Project description:BackgroundThe association between atopic dermatitis and childhood overweight and obesity has been studied extensively, but the results are inconclusive; most studies have focused on body mass index as a measure of obesity, with few investigating the relationship with underweight. Therefore, this study aimed to investigate the association between body mass index levels and atopic dermatitis in Korean adolescents.Methods3-year (2019-2021) of Korea Youth Risk Behavior Web-based Survey were used. Body mass index was used to measure obesity and a recent diagnosis within the past year was used as the criterion for atopic dermatitis. Multiple logistic regression analyses were performed to explore the associations. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsA total of 144,183 adolescents aged 12-18 years were included in this study (74,704 males and 69,479 females). Over the past year, 5.4% of males and 7.3% of females were diagnosed with atopic dermatitis in the study population. Adolescents with normal weight (males [OR: 1.19, CI: 1.02-1.38]; females [OR: 1.26, CI: 1.10-1.43]) and overweight (males [OR: 1.37, CI: 1.16-1.61]; females [OR: 1.37, CI: 1.19-1.58]) were more likely to develop atopic dermatitis than underweight.ConclusionIncreased degree of obesity may contribute to the development of atopic dermatitis. The normal-weight and obese adolescents had higher likelihood of developing atopic dermatitis compared with the underweight adolescents.
| S-EPMC11259265 | biostudies-literature
Project description:Accumulating evidence indicates a correlation between gut microbiota (GM) and atopic dermatitis (AD). Nevertheless, the causal relationship between specific pathogenic bacterial taxa and AD remains uncertain. This investigation utilized a two-sample Mendelian randomization (MR) analysis to assess the causal association between GM and AD, identifying the most influential GM taxa. An MR study was conducted utilizing summary statistics derived from genome-wide association studies encompassing 207 GM taxa and their association with AD risk. The genome-wide association studies summary statistics for 207 GM taxa (from phylum to species level) were generated by the Dutch Microbiome Project. The genetic variants (P < 1 × 10-5) correlated with GM (n = 7738) were identified from this investigation. Additionally, 4 supplementary MR approaches, simple mode, MR-Egger, weighted mode, and weighted median, supported the inverse-variance weighted approach. Furthermore, sensitivity analyses were executed using leave-one-out analysis, Cochran Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier global test, and MR Steiger test. The MR analysis identified 17 distinct bacterial taxa involving 2 orders, 4 families, 5 genera, and 6 species. The inverse-variance weighted method demonstrated that 6 bacterial taxa were positively associated with AD. These taxa included the order Pasteurellales, family Burkholderiales noname, family Pasteurellaceae, genus Burkholderiales noname, species Burkholderiales bacterium_1_1_47, and species Desulfovibrio piger. Eleven bacterial taxa were negatively associated with AD, comprising the order Actinomycetales, family Micrococcaceae, family Oscillospiraceae, genus Rothia, genus Collinsella, genus Oscillibacter, genus Pseudoflavonifractor, species Oscillibacter_unclassified, species Roseburia hominis, species R mucilaginosa, and species Parabacteroides merdae. Moreover, the MR-Egger intercept test and MR pleiotropy residual sum and outlier global test validated that the MR analysis remained unaffected by horizontal pleiotropy (P > .05). Furthermore, the leave-one-out analysis contributed to validating the robustness of the outcomes. Finally, an MR Steiger directionality test confirmed the assessment of potential causal direction (P < .001). This investigation identified specific intestinal flora causally associated with AD risk, offering novel insights for future investigations and innovative avenues for AD diagnosis, therapeutic intervention, and prognostic assessment.
| S-EPMC11688022 | biostudies-literature
Project description:Previous studies suggest that a high body mass index (BMI) may be a risk factor for keratoconus (KC), but the causal relationship remains unclear. This study used Mendelian randomization (MR) to investigate this connection and explore the mediating role of circulating serum metabolites and inflammatory factors in this association. Two-sample MR analysis was conducted to assess the relationship between BMI and KC. The study employed a two-step MR approach to evaluate the mediating roles of 91 inflammatory markers and 249 serum metabolites in the BMI-KC relationship. Inverse variance weighting (IVW) was the primary method, and multiple sensitivity analyses were performed to ensure robustness. IVW analysis revealed a positive causal relationship between BMI and KC (OR IVW = 1.811, 95% CI 1.005-3.262, P = 0.048). Although IL-12β and IL-4 were causally associated with KC, they did not mediate the BMI-KC relationship. Five serum metabolites were identified as potential mediators, with HDL cholesterol and triglyceride ratios showing significance. This study clarified the causal relationship between high BMI and KC, suggesting that high BMI may induce KC through lipid metabolism abnormalities. These findings underscore the importance of managing BMI for KC prevention.
| S-EPMC11467444 | biostudies-literature
Project description:Newly emerging evidence indicates that body mass index (BMI) is a potential risk factor for autoimmune diseases (ADs). Nevertheless, the exact causal connection between ADs and BMI in children remains uncertain. To investigate the relationship between BMI in children and ADs, a 2-sample Mendelian randomization (MR) analysis was conducted. In this analysis, several regression methods were utilized, including the inverse-variance weighted (IVW), weighted mode, weighted median, and MR-Egger regression. Publicly available summary statistics datasets from meta-analyses of genome-wide association studies (GWAS) were employed, specifically focusing on BMI in children of European descent (n = 39,620) from the UK Biobank (ebi-a-GCST90002409) as the exposure group. The outcomes were derived from individuals included in the Finnish biobank study FinnGen, with 42,202 cases and 176,590 controls representing the ADs group (finngen_R5_AUTOIMMUNE). For instrumental variables, we carefully selected 16 single nucleotide polymorphisms (SNPs) from GWAS on BMI in children. Our analysis implemented the IVW method, which demonstrated supporting evidence for a causal association between BMI in children and ADs. The results indicated a significant effect with a beta coefficient of 0.22, standard error (SE) of 0.05, odds ratio (OR) of 1.25, and a 95% confidence interval (CI) ranging from 1.13 to 1.38, with a P-value of <.05. We also utilized the weighted median method, which yielded similar findings to the IVW method. The OR estimates from the weighted median analysis showed a beta coefficient of 0.20, SE of 0.06, OR of 1.22, and a 95% CI ranging from 1.08 to 1.36, with a P-value of <.05. No significant association was observed in the MR-Egger and Weighted mode analyses. The findings from the MR analysis suggest that there is evidence supporting a potential causal link between BMI in children and an increased susceptibility to ADs.
| S-EPMC11479409 | biostudies-literature
Project description:BackgroundIt is unclear whether the relationship between cigarette smoking and atopy is mediated by body fat mass, such as the Body Mass Index (BMI). We assessed the mediating role of BMI on the relationship between smoking and atopy in Chinese adults.MethodsA hospital-based case-control study of 786 atopic cases and 2771 controls was conducted in adults aged 18 years or older from March 2010 to September 2014 in Harbin, China. Mediation models were used to estimate the indirect effects of smoking on atopic sensitization through BMI.ResultsCompared to non-smokers, light smokers and moderate smokers had a lower risk of inhalant allergen sensitization. The indirect effect of smoking and sensitization to aeroallergens were only observed in light smokers (point estimate, -0.026; 95% CI, -0.062 to -0.004). The mediating roles of BMI on the relationships between smoking and other types of allergic sensitization were not statistically significant.ConclusionBMI appeared to partially mediate the effect of light smoking on sensitization to aeroallergens. However, considering the other harmful health effects of cigarette smoking, the effective method to lower the incidence of atopy would be to decrease body fat mass by physical exercise and employing other more healthy ways of living rather than smoking.
| S-EPMC4377972 | biostudies-literature