Genome-wide meta-analysis identifies novel loci conferring risk of acne vulgaris

Teder‐Laving, Maris; Kals, Mart; Reigo, Anu; Ehin, Riin; Objärtel, Telver; Vaht, Mariliis; Nikopensius, Tiit; Metspalu, Andres; Kingo, Külli

doi:10.1038/s41431-023-01326-8

Cited by 7 publications

(7 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FADS2 is a gene associated with lipid metabolism, upregulation of its expression can induce pro-inflammatory sebaceous gland activity (Zouboulis and Angres, 2021). Recent genome-wide association studies and meta-analysis have shown that FADS2 is a risk gene for acne vulgaris (Teder-Laving et al, 2023). TIMP-3 is a secreted protein that has a broad inhibitory effect on matrix metalloproteinases (MMPs).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris

Wu,

Wang,

et al. 2024

Front. Microbiol.

View full text Add to dashboard Cite

BackgroundNumerous studies have suggested a correlation between gut microbiota and acne vulgaris; however, no specific causal link has been explored.Materials and methodsTo investigate the possible causal relationship between gut microbiota and acne vulgaris, this study employed a large-scale genome-wide association study (GWAS) summary statistic. Initially, a two-sample Mendelian randomization (MR) analysis was utilized to identify the specific gut microflora responsible for acne vulgaris. We used the Inverse Variance Weighted (IVW) method as the main MR analysis method. Additionally, we assessed heterogeneity and horizontal pleiotropy, while also examining the potential influence of individual single-nucleotide polymorphisms (SNPs) on the analysis results. In order to eliminate gut microbiota with reverse causal associations, we conducted reverse MR analysis. Multivariate Mendelian randomization analysis (MVMR) was then employed to verify the independence of the causal associations. Finally, we performed SNP annotation on the instrumental variables of independent gut microbiota and acne vulgaris to determine the genes where these genetic variations are located. We also explored the biological functions of these genes through enrichment analysis.ResultThe IVW method of forward MR identified nine gut microbes with a causal relationship with acne vulgaris (p < 0.05). The findings from the sensitivity analysis demonstrate the absence of heterogeneity or horizontal pleiotropy, and leave-one-out analysis indicates that the results are not driven by a single SNP. Additionally, the Reverse MR analysis excluded two reverse-correlated pathogenic gut microbes. And then, MVMR was used to analyze seven gut microbes, and it was found that Cyanobacterium and Family XIII were risk factors for acne vulgaris, while Ruminococcus1 and Ruminiclostridium5 were protective factors for acne vulgaris. After conducting biological annotation, we identified six genes (PLA2G4A, FADS2, TIMP17, ADAMTS9, ZC3H3, and CPSF4L) that may be associated with the pathogenic gut microbiota of acne vulgaris patients. The enrichment analysis results indicate that PLA2G4A/FADS2 is associated with fatty acid metabolism pathways.ConclusionOur study found independent causal relationships between four gut microbes and acne vulgaris, and revealed a genetic association between acne vulgaris patients and gut microbiota. Consider preventing and treating acne vulgaris by interfering with the relative content of these four gut microbes.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Acne vulgaris data are derived from GWAS studies and metaanalyses in European cohorts of EstBB, FinnGen and Lifelines, including 34,422 acne patients and 364,991 normal controls (Teder-Laving et al, 2023).…”

Section: Data Sourcesmentioning

confidence: 99%

Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris

Wu,

Wang,

et al. 2024

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…The serum metabolite data were derived from a GWAS of 486 metabolites in blood from 7824 adults from two European populations, published by SoYoun Shin et al The 309 known metabolites were selected from this dataset 19 . The data on acne vulgaris were derived from a GWAS data of 34,422 patients with acne and 364,991 controls from three independent cohorts of European ancestry, published by Maris Teder-Laving et al in 2023 20 .…”

Section: Methodsmentioning

confidence: 99%

The causal relationship between serum metabolites and acne vulgaris: a Mendelian randomization study

Wang,

Wu,

Zhao

et al. 2024

Sci Rep

View full text Add to dashboard Cite

In individuals with acne vulgaris, alterations occur in serum metabolite composition, yet the exact causal link between these metabolites and acne development remains elusive. Using genome-wide association datasets, we performed bidirectional Mendelian randomization (MR) to investigate the potential causal relationship between 309 serum metabolites and acne vulgaris. We performed sensitivity analysis to evaluate the presence of heterogeneity and pleiotropy. Forward MR analysis found 14 serum metabolites significantly associated with acne vulgaris, and reverse MR analysis found no significant association between acne vulgaris and these serum metabolites. Through validation using data from the FinnGen database of acne vulgaris studies, we found a conclusive and significant correlation between stearoylcarnitine and acne vulgaris. This provides new evidence in the search for new targets for the treatment of acne vulgaris.

show abstract

“… 19 For acne vulgaris, insights were integrated from the study by Teder‐Laving et al., which included 34 422 cases and 364 991 controls, identifying novel risk loci. 20 Genetic summaries for atopic dermatitis, psoriasis vulgaris, and urticaria were also sourced from the IEU Open GWAS database, with populations of 6224, 5072, and 1057 cases, respectively, and corresponding controls numbering 475 075, 478 102, and 482 892. 19 GWAS data for rosacea, involving 1195 cases and 211 139 controls, were procured from the FinnGen research consortium ( https://gwas.mrcieu.ac.uk/datasets/finn‐b‐L12_ROSACEA/ ).…”

Section: Methodsmentioning

confidence: 99%

Causal relationship between inflammatory skin diseases and breast cancer: A bidirectional Mendelian randomization study

Yang,

Zhao

2024

Skin Research and Technology

View full text Add to dashboard Cite

IntroductionPrior research has explored the relationship between inflammatory skin disorders and breast cancer (BC), yet the causality of this association remains uncertain.MethodsUtilizing a bidirectional two‐sample Mendelian randomization (MR) approach, this study aimed to elucidate the causal dynamics between various inflammatory skin conditions—namely acne, atopic dermatitis, psoriasis vulgaris, urticaria, and rosacea—and BC. Genetic variants implicated in these disorders were sourced from comprehensive genome‐wide association studies representative of European ancestry. In the forward MR, BC was posited as the exposure, while the reverse MR treated each inflammatory skin disease as the exposure. A suite of analytical methodologies, including random effects inverse variance weighted (IVW), weighted median (WME), and MR‐Egger, were employed to probe the causative links between inflammatory skin diseases and BC. Sensitivity analyses, alongside evaluations for heterogeneity and pleiotropy, were conducted to substantiate the findings.ResultsThe MR analysis revealed an increased risk of acne associated with BC (IVW: OR = 1.063, 95% CI = 1.011–1.117, p = 0.016), while noting a decreased risk of atopic dermatitis (AD) in BC patients (IVW: OR = 0.941, 95% CI = 0.886–0.999, p = 0.047). No significant associations were observed between BC and psoriasis vulgaris, urticaria, or rosacea. Conversely, reverse MR analyses detected no effect of BC on the incidence of inflammatory skin diseases. The absence of pleiotropy and the consistency of these outcomes strengthen the study's conclusions.ConclusionFindings indicate an elevated incidence of acne and a reduced incidence of AD in individuals with BC within the European population.

show abstract

Genome-wide meta-analysis identifies novel loci conferring risk of acne vulgaris

Cited by 7 publications

References 55 publications

Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris

Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris

The causal relationship between serum metabolites and acne vulgaris: a Mendelian randomization study

Causal relationship between inflammatory skin diseases and breast cancer: A bidirectional Mendelian randomization study

Contact Info

Product

Resources

About