Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

Navarini, Alexander A.; Simpson, Michael A.; Weale, Michael E.; Knight, Jo; Carlavan, Isabelle; Reiniche, Pascale; Burden, David; Layton, Alison; Bataille, Véronique; Allen, Michael; Pleass, Robert; Pink, Andrew E.; Creamer, Daniel; English, John; Munn, S.E.; Walton, Shernaz; Willis, Carolyn; Déret, Sophie; Voegel, Johannes J.; Spector, Tim D.; Smith, Catherine; Trembath, Richard C.; Barker, Jonathan

doi:10.1038/ncomms5020

Cited by 73 publications

(74 citation statements)

References 44 publications

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“…Genome‐wide arrays, genomic genotyping technologies and computing power have now made it feasible, and affordable, to approach genetic associations with large case–control study designs. Five genome‐wide association studies (GWASs) for acne vulgaris have been completed in four distinct geographical locations covering North America, Northern Europe, China and Australia . Four studies recruited Caucasian patients and the fifth was performed with a cohort of Han Chinese patients.…”

Section: Genome‐wide Association Studiesmentioning

confidence: 99%

What does acne genetics teach us about disease pathogenesis?

2019

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Summary Background Acne vulgaris is a highly prevalent inflammatory skin disorder with a complex pathogenesis, characterized by comedones, papules, pustules and nodules. Familial preponderance clearly indicates a genetic basis for acne vulgaris, but until recently solid genetic associations were lacking. Results The advent of high‐resolution genotyping array technologies has allowed for large‐scale studies with both family‐based and cross‐sectional designs. These studies have revealed genetic loci encompassing genes that could be active in biological pathways and processes underlying acne vulgaris. However, specific functional consequences of those variants remain elusive. In parallel, investigations into rare disorders and syndromes that incorporate features of acne or acne‐like lesions have recently accelerated our understanding of disease pathogenesis. The genes revealed by these rare disorders highlight mechanisms cardinal for pilosebaceous biology and therefore anchor our insights from genetic association studies for acne vulgaris. Conclusions The next phase of research will require more in‐depth mechanistic investigations of loci and genes implicated in acne phenotypes to define the key molecular players driving the disorder. Concurrently, new treatments for acne vulgaris could be developed by dissecting the candidate molecular pathways to identify druggable targets.

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Section: Genome‐wide Association Studiesmentioning

confidence: 99%

What does acne genetics teach us about disease pathogenesis?

2019

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“…Relevant gene polymorphisms have been found in various genes, including those encoding the androgen receptor, enzymes of androgen metabolism (cytochrome P450 1A1 or 21-hydroxylase), tumor necrosis factor-α (TNF α ), and insulin-like growth factor 1 (IGF-1). Genome-wide analysis has shown an association of severe acne with genes of the transforming growth factor-β (TGF β )-mediated signaling cascade [ 11 ] .…”

Section: Genetic Backgroundmentioning

confidence: 99%

“…10 Indirect evidence from nodular acne and conglobate acne as well as expert opinion. 11 Indirect evidence from severe papulopustular acne. 12 Indirect evidence from a study that also used chlorhexidine, recommendation is also based on expert opinion.…”

Section: Patient Managementmentioning

confidence: 99%

Acne

Degitz

Ochsendorf

2017

J Deutsche Derma Gesell

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Summary Acne is a chronic disease with a high prevalence among adolescents. Key pathogenetic factors (and their clinical correlates) are increased sebum production (seborrhea), follicular hyperkeratosis (comedones), and perifollicular inflammation (papules and pustules). The disease is modulated by a variety of endogenous (androgens, IGF‐1, neuroendocrine factors) and exogenous (Propionibacterium acnes, diet, friction, ingredients of medical or cosmetic topical products) triggers. Acne is associated with high morbidity, and even mild manifestations may potentially cause considerable impairment in quality of life. Effective topical and systemic treatments are available. Optimal therapeutic results require continuous patient management over the course of the entire treatment period as well as adjustment of treatment modalities based on symptoms and disease severity.

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“…Over the past several decades, a large set of genes and genomic regions involved in acne susceptibility were revealed through linkage analysis and association studies, including human leukocyte antigen class II haplotypes, DDB2 and SELL . The number of convincingly established genetic associations with acne has increased sharply using genome‐wide association study (GWAS) and relative studies . Interaction studies among parts of these associated loci would be important for clarifying the biological and biochemical pathways that underlie the disease.…”

Section: Introductionmentioning

confidence: 99%

Variants in SELL,MRPS36P2,TP63,DDB2,CACNA1H,ADAM19,GNAI1,CDH13 and GABRG2 interact to confer risk of acne in Chinese population

Wang

Guo

Shen

et al. 2015

The Journal of Dermatology

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Acne vulgaris is a common skin disease characterized by chronic inflammation of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinization, inflammation and bacterial colonization of hair follicles by propionibacterium acnes. Our previous genome-wide association study on acne has identified two new susceptibility loci. To search for potential gene-gene interactions and investigate the best-fit association models for the single nucleotide polymorphisms (SNP) from these interacting genes, we implemented logistic regression analysis in the combined sample of 2916 cases with severe acne and 4716 controls. The most significant association evidence was observed under an additive model for rs6896064 and under a dominant model the rest of these SNP. Significant interactions between these SNP were observed in this study: the SELL × MRPS36P2 (Padjusted = 4.15 × 10(-10)), TP63 × DDB2 (Padjusted = 7.62 × 10(-08)), DDB2 × CACNA1H (Padjusted = 1.89 × 10(-07)), ADAM19 × GNAI1 × CDH13 (Padjusted = 1.22 × 10(-04)) and ADAM19 × GABRG2 × GNAI2 × CDH13 (Pad justed = 6.33 × 10(-05)). These results may contribute to our understanding of acne genetic etiology and account for the additional risk of certain patients.

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Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

Cited by 73 publications

References 44 publications

What does acne genetics teach us about disease pathogenesis?

What does acne genetics teach us about disease pathogenesis?

Acne

Variants in SELL,MRPS36P2,TP63,DDB2,CACNA1H,ADAM19,GNAI1,CDH13 and GABRG2 interact to confer risk of acne in Chinese population

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