Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
About GenEpi
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
40666320
TITLE
Genome-wide association meta-regression identifies stem cell lineage orchestration as a key driver of acne risk.
ABSTRACT
Over 85% of the population experience acne at some point in their lives, with its severity spanning 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. The analytical approach taken in this study aimed to address the impact of variation in the dichotomisation of acne case control status, driven by ascertainment and study design, on effect size estimates across independent genetic association studies of acne. Through a fixed intercept meta-regression framework, we combined evidence genome-wide for association with acne across studies in which case-control status had been ascertained in different settings, allowing for different severity threshold definitions. Across a combined sample of 73,997 cases and 1,103,940 controls of European, South Asian and African American ancestry we identify genetic variation at 165 genomic loci that influence acne risk. There is evidence for both shared and ancestry specific components to the genetic susceptibility to acne and for sex differences in the magnitude of effect of risk alleles at three loci. We observe that common genetic variation explains 13.4% of acne heritability on the liability scale. Consistent with the hypothesis that genetic risk primarily operates at the level of individual pilosebaceous units, a polygenic score derived from this case-control study of acne susceptibility is associated with both self-reported and clinically assessed acne severity in adolescence, further strengthening the link between genetic risk and disease severity. Prioritisation of causal genes at the identified acne risk loci, provides genetic validation of the targets of established and emerging acne therapies, including retinoid treatments. The identified acne risk loci are enriched for genes encoding downstream effectors of signalling, including and components of the and p53 pathways. Illustrating that the control of stem cell lineage plasticity and cellular fate are important mechanisms through which genetic variation influences acne susceptibility within the pilosebaceous unit.
DATE PUBLISHED
2025 Jun 28
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2025/07/16 06:25
medline 2025/07/16 06:26
entrez 2025/07/16 05:29
pmc-release 2025/07/15
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Maxwell J Maxwell Jessye J Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, United Kingdom.
Mitchell BL Mitchell Brittany L BL School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
DuHarpur X DuHarpur Xinyi X St John's Institute of Dermatology, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
Pardo LM Pardo Luba M LM Department of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Witkam WCAM Witkam Willemijn C A M WCAM Department of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Dand N Dand Nick N Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, United Kingdom.
Bartels M Bartels Meike M Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
Betti MJ Betti Michael J MJ Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Boomsma DI Boomsma Dorret I DI Amsterdam Reproduction & Development (AR&D) research institute, Amsterdam, the Netherlands.
Dong X Dong Xianjun X Adams Center of Parkinson's Disease Research, Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT, USA.
Gerring Z Gerring Zachary Z Walter and Eliza Hall Institute of Medical Research, VIC, Australia.
Finer S Finer Sarah S Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
Genes & Health Research Team
Hagenbeek FA Hagenbeek Fiona A FA Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
Hottenga JJ Hottenga Jouke Jan JJ Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
Hripcsak G Hripcsak George G Department of Biomedical Informatics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Huilaja L Huilaja Laura L Medical Research Center, Oulu University Hospital, Oulu, Finland.
Hveem K Hveem Kristian K Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
Jacobs BM Jacobs Benjamin M BM Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
Kals M Kals Mart M Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Kaufman-Cook J Kaufman-Cook James J Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, United Kingdom.
Kettunen J Kettunen Johannes J Systems Epidemiology, Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland.
Khan A Khan Atlas A Division of Nephrology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Kingo K Kingo Külli K Tartu University Hospital, Tartu, Estonia.
Kiryluk K Kiryluk Krzysztof K Division of Nephrology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Løset M Løset Mari M Department of Dermatology, Clinic of Orthopaedy, Rheumatology and Dermatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Lunter G Lunter Gerton G Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Lupton MK Lupton Michelle K MK School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
Min JL Min Josine L JL Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Martin NG Martin Nicholas G NG School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
Medland SE Medland Sarah E SE School of Psychology and Counselling, Queensland University of Technology (QUT), Brisbane, Australia.
Neijzen D Neijzen Dorien D Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Nijsten TEC Nijsten Tamar E C TEC Department of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Nikopensius T Nikopensius Tiit T Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Olsen CM Olsen Catherine M CM Population Health program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Petukhova L Petukhova Lynn L Department of Population Health, NYU Grossman School of Medicine, NYU Langone Health, New York, New York, USA.
Reigo A Reigo Anu A Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Rentería ME Rentería Miguel E ME School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
Rispoli R Rispoli Rossella R Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, United Kingdom.
Saklatvala J Saklatvala Jake J Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, United Kingdom.
Sliz E Sliz Eeva E Systems Epidemiology, Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland.
Tasanen-Määttä K Tasanen-Määttä Kaisa K Medical Research Center, Oulu University Hospital, Oulu, Finland.
Thomas L Thomas Laurent L BioCore - Bioinformatics Core Facility, NTNU - Norwegian University of Science and Technology, Trondheim. Norway.
Trembath RC Trembath Richard C RC Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, United Kingdom.
Vaht M Vaht Mariliis M Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
van Heel DA van Heel David A DA Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Weng C Weng Chunhua C Department of Biomedical Informatics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Whiteman DC Whiteman David C DC Population Health program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Barker JN Barker Jonathan N JN St John's Institute of Dermatology, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
Smith C Smith Catherine C St John's Institute of Dermatology, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
Simpson MA Simpson Michael A MA Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, United Kingdom.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: medRxiv : the preprint server for health sciences
ISOABBREVIATION: medRxiv
YEAR: 2025
MONTH: Jun
DAY: 28
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN:
ISSNTYPE:
MEDLINE JOURNAL
MEDLINETA: medRxiv
COUNTRY: United States
ISSNLINKING:
NLMUNIQUEID: 101767986
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Preprint
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
RC2 MH089951 NIMH NIH HHS United States
U01 HG008676 NHGRI NIH HHS United States
R01 MH081802 NIMH NIH HHS United States
RC2 MH089995 NIMH NIH HHS United States
U01 HG008657 NHGRI NIH HHS United States
R01 HD042157 NICHD NIH HHS United States
R01 AR080796 NIAMS NIH HHS United States
U01 HG008672 NHGRI NIH HHS United States
U01 HG008679 NHGRI NIH HHS United States
U01 HG008666 NHGRI NIH HHS United States
U24 MH068457 NIMH NIH HHS United States
U54 MD007593 NIMHD NIH HHS United States
U01 HG008685 NHGRI NIH HHS United States
U01 HG006379 NHGRI NIH HHS United States
U01 HG008664 NHGRI NIH HHS United States
U01 HG008701 NHGRI NIH HHS United States
U01 HG008684 NHGRI NIH HHS United States
EP-C-15-001 EPA United States
K01 AR075111 NIAMS NIH HHS United States
U01 HG008680 NHGRI NIH HHS United States
TL1 TR001875 NCATS NIH HHS United States
Wellcome Trust United Kingdom
U01 HG008673 NHGRI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
Designed by: GenEpi IT
Maintained by: GenEpi IT
Feedback: webmaster
Copyright © 2007 QIMR
For more information Contact Us
epiit@qimr.edu.au
Last Modified: Oct 15 2007