O10 Acne polygenic risk score derived from genome-wide association metaregression enables prediction of severity

Abstract Acne vulgaris is highly prevalent, with 85% of the population experiencing it at some point in their lives. Disease severity spans a quantitative spectrum, from mild, transient outbreaks to more persistent, severe forms of the condition. Moderate-to-severe disease poses a substantial global burden arising from both the physical and psychological impacts of this highly visible condition (Layton AM, Thiboutot D, Tan J. Reviewing the global burden of acne: how could we improve care to reduce the burden? Br J Dermatol 2021; 184: 219–25). Acne pathogenesis is due to factors contributing to comedogenesis and inflammation within the pilosebaceous unit. This study aims to characterize the genetic contribution to acne through a genome-wide association metaregression. Through a fixed-intercept metaregression framework, we combined evidence from genome-wide studies encompassing 73 997 cases and 1 103 940 controls of European, South Asian and African American ancestry. Our approach addressed the impact of variation in the dichotomization of acne case–control status, enabling generation of a more accurate polygenic risk score (PRS) for acne. We evaluated the performance of our PRS using two independent cohorts totalling 4540 individuals with varying acne severity. Our study also incorporated identification of ancestry-specific components to genetic susceptibility, as well as sex-stratified analysis. We identified genetic variation at 165 genomic loci that influence acne risk and found that common genetic variation explains 13.4% of acne heritability on the liability scale. We established evidence for both shared and ancestry-specific components to the genetic susceptibility to acne, and identified sex differences in the magnitude of effect of risk alleles at three loci. PRS performance was initially evaluated using an independent cohort of 2058 individuals with self-reported acne (severity classed as none, mild, moderate, severe). We found that the mean of the PRS distribution significantly increased with self-reported disease severity, with one SD increase in PRS corresponding to 1.63-fold increase in the likelihood of reporting more severe disease. To further validate this tool, we then investigated the distribution of PRS in a cross-sectional cohort of 2482 teenage patients. Within this cohort acne severity was categorized (clear/almost clear, mild, moderate/severe) by trained dermatologists from three-dimensional facial photographs taken at age ∼13 years. Consistently with the findings for self-reported acne, a single SD increase in polygenic risk corresponded to a 1.53-fold increase in the odds of being one severity category higher. A PRS model derived from a genome-wide association metaregression enables prediction of acne severity, demonstrating proof-of-principle of a genomics-based precision medicine tool.

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Publication Details

Journal
British Journal of Dermatology
Published
2025-06-27
DOI
https://doi.org/10.1093/bjd/ljaf085.025
Citations
1
Primary Topic
Acne and Rosacea Treatments and Effects
Type
article
Field-Weighted Citation Impact
2.00
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article

O10 Acne polygenic risk score derived from genome-wide association metaregression enables prediction of severity

Tamar E. C. Nijsten, Mart Kals, Külli Kingo, Kaisa Tasanen-Määttä et al.
1 citations
British Journal of Dermatology
Acne and Rosacea Treatments and Effects
2.00
article

O10 Acne polygenic risk score derived from genome-wide association metaregression enables prediction of severity

Tamar E. C. Nijsten, Mart Kals, Külli Kingo, Kaisa Tasanen-Määttä, Luba M. Pardo, Nick Dand, Sarah Elizabeth Medland, Nicholas G. Martin, Josine L. Min, Benjamin M. Jacobs, Xinyi Du-Harpur, David A. van Heel, Michelle K. Lupton, Miguel E. Rentería, Michael J. Betti, Atlas Khan, Johannes Kettunen, Laura Huilaja, David C. Whiteman, Jouke‐Jan Hottenga, Fiona A. Hagenbeek, Meike Bartels, Mariliis Vaht, Kristian Hveem, Jessye Maxwell, Michael A. Simpson, Richard C. Trembath, Jake Saklatvala, Anu Reigo, Catherine M. Olsen, James Kaufman-Cook, Krzysztof Kiryluk, Brittany L. Mitchell, Chunhua Weng, George Hripcsak, Xianjun Dong, Gerton A. Lunter, Sarah Finer, Juliet N. Barker, Lynn Petukhova, Tiit Nikopensius, Dorret Irene Boomsma, Laurent F. Thomas, Eeva Sliz, Rossella Rispoli, Mari Løset, Zachary F. Gerring, Catherine Smith, Dorien Neijzen, Willemijn C. A. M. Witkam
article en
1 citations

Abstract

Abstract Acne vulgaris is highly prevalent, with 85% of the population experiencing it at some point in their lives. Disease severity spans a quantitative spectrum, from mild, transient outbreaks to more persistent, severe forms of the condition. Moderate-to-severe disease poses a substantial global burden arising from both the physical and psychological impacts of this highly visible condition (Layton AM, Thiboutot D, Tan J. Reviewing the global burden of acne: how could we improve care to reduce the burden? Br J Dermatol 2021; 184: 219–25). Acne pathogenesis is due to factors contributing to comedogenesis and inflammation within the pilosebaceous unit. This study aims to characterize the genetic contribution to acne through a genome-wide association metaregression. Through a fixed-intercept metaregression framework, we combined evidence from genome-wide studies encompassing 73 997 cases and 1 103 940 controls of European, South Asian and African American ancestry. Our approach addressed the impact of variation in the dichotomization of acne case–control status, enabling generation of a more accurate polygenic risk score (PRS) for acne. We evaluated the performance of our PRS using two independent cohorts totalling 4540 individuals with varying acne severity. Our study also incorporated identification of ancestry-specific components to genetic susceptibility, as well as sex-stratified analysis. We identified genetic variation at 165 genomic loci that influence acne risk and found that common genetic variation explains 13.4% of acne heritability on the liability scale. We established evidence for both shared and ancestry-specific components to the genetic susceptibility to acne, and identified sex differences in the magnitude of effect of risk alleles at three loci. PRS performance was initially evaluated using an independent cohort of 2058 individuals with self-reported acne (severity classed as none, mild, moderate, severe). We found that the mean of the PRS distribution significantly increased with self-reported disease severity, with one SD increase in PRS corresponding to 1.63-fold increase in the likelihood of reporting more severe disease. To further validate this tool, we then investigated the distribution of PRS in a cross-sectional cohort of 2482 teenage patients. Within this cohort acne severity was categorized (clear/almost clear, mild, moderate/severe) by trained dermatologists from three-dimensional facial photographs taken at age ∼13 years. Consistently with the findings for self-reported acne, a single SD increase in polygenic risk corresponded to a 1.53-fold increase in the odds of being one severity category higher. A PRS model derived from a genome-wide association metaregression enables prediction of acne severity, demonstrating proof-of-principle of a genomics-based precision medicine tool.

British Journal of DermatologyVol. 193(Supplement_1)
Brigham and Women's Hospital (US), University of Helsinki (FI), Queensland University of Technology (AU), The University of Queensland (AU), Queen Mary University of London (GB), University of Groningen (NL), King's College London (GB), Walter and Eliza Hall Institute of Medical Research (AU), Guy's and St Thomas' NHS Foundation Trust (GB), Norwegian University of Science and Technology (NO), QIMR Berghofer Medical Research Institute (AU), Oulu University Hospital (FI), Levanger Hospital (NO), Erasmus MC (NL), Tartu University Hospital (EE), Yale University (US), University of Bristol (GB), NYU Langone Health (US), St Olav's University Hospital (NO), Institute of Dermatology (TH), University of Tartu (EE), Columbia University (US), Vrije Universiteit Amsterdam (NL), Vanderbilt University Medical Center (US), University of Oulu (FI)
Openalex Percentile: Top 14%
Acne and Rosacea Treatments and Effects
2.00
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