Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes

Schmitt, Jochen; Schwarz, Kristin; Baurecht, Hansjörg; Hotze, Melanie; Fölster‐Holst, Regina; Rodríguez, Elke; Lee, Young A.E.; Franke, André; Degenhardt, Frauke; Lieb, Wolfgang; Gieger, Christian; Kabesch, Michael; Nöthen, Markus M.; Irvine, Alan D.; McLean, W. H. Irwin; Deckert, Stefanie; Stephan, V.; Schwarz, Peter E. H.; Aringer, Martin; Novak, Natalija; Weidinger, Stephan

doi:10.1016/j.jaci.2015.06.029

Cited by 173 publications

(178 citation statements)

References 63 publications

(58 reference statements)

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…This haplogroup also carries the primary susceptibility variant in Asians, and is the primary contributor to a significant signal of the selective sweep observed in Chinese population. A combination of these physically linked variants may have contributed to atopic dermatitis susceptibility, as well as other allergic reactions known to co-occur with atopic dermatitis, such as rheumatoid arthritis and inflammatory bowel disease (Schmitt et al 2016). In addition, it is likely that a currently unknown adaptive force acting on one of these variants is the primary driver for the observed selective sweep.…”

Section: Resultsmentioning

confidence: 99%

Atopic Dermatitis Susceptibility Variants in FilaggrinHitchhikeHornerin Selective Sweep

Eaaswarkhanth

Flanagan

et al. 2016

Genome Biol Evol

View full text Add to dashboard Cite

Human skin has evolved rapidly, leaving evolutionary signatures in the genome. The filaggrin (FLG) gene is widely studied for its skin-barrier function in humans. The extensive genetic variation in this gene, especially common loss-of-function (LoF) mutations, has been established as primary risk factors for atopic dermatitis. To investigate the evolution of this gene, we analyzed 2,504 human genomes and genotyped the copy number variation of filaggrin repeats within FLG in 126 individuals from diverse ancestral backgrounds. We were unable to replicate a recent study claiming that LoF of FLG is adaptive in northern latitudes with lower ultraviolet light exposure. Instead, we present multiple lines of evidence suggesting that FLG genetic variation, including LoF variants, have little or no effect on fitness in modern humans. Haplotype-level scrutinization of the locus revealed signatures of a recent selective sweep in Asia, which increased the allele frequency of a haplotype group (Huxian haplogroup) in Asian populations. Functionally, we found that the Huxian haplogroup carries dozens of functional variants in FLG and hornerin (HRNR) genes, including those that are associated with atopic dermatitis susceptibility, HRNR expression levels and microbiome diversity on the skin. Our results suggest that the target of the adaptive sweep is HRNR gene function, and the functional FLG variants that involve susceptibility to atopic dermatitis, seem to hitchhike the selective sweep on HRNR. Our study presents a novel case of a locus that harbors clinically relevant common genetic variation with complex evolutionary trajectories.

show abstract

Section: Resultsmentioning

confidence: 99%

Atopic Dermatitis Susceptibility Variants in FilaggrinHitchhikeHornerin Selective Sweep

Eaaswarkhanth

Flanagan

et al. 2016

Genome Biol Evol

View full text Add to dashboard Cite

show abstract

“…It is to be noted that these comorbidities may be in addition to other comorbidities of AD which have been recently identified. For example, a German retrospective cohort study demonstrated that patients with AD were at increased risk for incident rheumatoid arthritis (risk ratio, 1.72; 95% confidence interval [CI], 1.25–2.37) with no disproportionate occurrence of known genetic risk alleles 31. A similar observation was reported in a study conducted in Taiwan, with a significant association between rheumatoid arthritis and atopy (hazard ratio, 1.74; 95% CI, 1.31–2.33) 32.…”

Section: Discussionmentioning

confidence: 99%

Burden of atopic dermatitis in Japanese adults: Analysis of data from the 2013 National Health and Wellness Survey

Arima

Gupta

Gadkari

et al. 2018

The Journal of Dermatology

View full text Add to dashboard Cite

Atopic dermatitis is a chronic inflammatory skin disease. The objective of this study was to characterize the burden of atopic dermatitis in Japanese adult patients relative to the general population. Japanese adults (≥18 years) with a self‐reported diagnosis of atopic dermatitis and adult controls without atopic dermatitis/eczema/dermatitis were identified from the 2013 Japan National Health and Wellness Survey. Atopic dermatitis patients were propensity‐score matched with non‐atopic dermatitis controls (1:2 ratio) on demographic variables. Patient‐reported outcome data on comorbidities, mood and sleep disorders, health‐related quality of life, work productivity and activity impairment, and health‐care resource utilization were analyzed in atopic dermatitis patients and matched controls. A total of 638 Japanese adult patients with atopic dermatitis were identified, of whom 290 (45.5%) rated their disease as “moderate/severe” and 348 (54.5%) as “mild”. The analysis cohort comprised 634 atopic dermatitis patients and 1268 matched controls. Atopic dermatitis patients reported a significantly higher prevalence of arthritis, asthma, nasal allergies/hay fever, anxiety, depression and sleep disorders compared with controls (all P < 0.001). Atopic dermatitis patients also reported a significantly poorer health‐related quality of life, higher overall work and activity impairment, and higher health‐care resource utilization (all P < 0.001). Self‐rated disease severity was not associated with disease burden, except for a significantly higher overall work and activity impairment. In conclusion, Japanese adult patients with atopic dermatitis reported a substantial disease burden relative to adults without atopic dermatitis, suggesting an unmet need for effective strategies targeting disease management.

show abstract

“…Patient stratification based on cell-specific transcriptomic data was recently reported (19, 20). In addition, comorbidity of immune disorders, for example, in patients with inflammatory bowel diseases, psoriasis, or rheumatoid arthritis (21, 22) demonstrates that common mechanisms probably underlie immune disorders (23). Recent work in the field of systems medicine (24, 25) shows commonalities at the molecular and cellular level between subgroups of patients diagnosed with different CIDs.…”

Section: Common Pathways In Cidsmentioning

confidence: 99%

Embracing Complexity beyond Systems Medicine: A New Approach to Chronic Immune Disorders

Velde

Bezema²,

Kampen

et al. 2016

Front. Immunol.

View full text Add to dashboard Cite

In order to combat chronic immune disorders (CIDs), it is an absolute necessity to understand the bigger picture, one that goes beyond insights at a one-disease, molecular, cellular, and static level. To unravel this bigger picture we advocate an integral, cross-disciplinary approach capable of embracing the complexity of the field. This paper discusses the current knowledge on common pathways in CIDs including general psychosocial and lifestyle factors associated with immune functioning. We demonstrate the lack of more in-depth psychosocial and lifestyle factors in current research cohorts and most importantly the need for an all-encompassing analysis of these factors. The second part of the paper discusses the challenges of understanding immune system dynamics and effectively integrating all key perspectives on immune functioning, including the patient’s perspective itself. This paper suggests the use of techniques from complex systems science in describing and simulating healthy or deviating behavior of the immune system in its biopsychosocial surroundings. The patient’s perspective data are suggested to be generated by using specific narrative techniques. We conclude that to gain more insight into the behavior of the whole system and to acquire new ways of combatting CIDs, we need to construct and apply new techniques in the field of computational and complexity science, to an even wider variety of dynamic data than used in today’s systems medicine.

show abstract

Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes

Cited by 173 publications

References 63 publications

Atopic Dermatitis Susceptibility Variants in FilaggrinHitchhikeHornerin Selective Sweep

Atopic Dermatitis Susceptibility Variants in FilaggrinHitchhikeHornerin Selective Sweep

Burden of atopic dermatitis in Japanese adults: Analysis of data from the 2013 National Health and Wellness Survey

Embracing Complexity beyond Systems Medicine: A New Approach to Chronic Immune Disorders

Contact Info

Product

Resources

About