Genome-wide association meta-analysis identifies 29 new acne susceptibility loci

Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.

3 nature research | reporting summary April 2020 Commonly misidentified lines (See ICLAC register) Palaeontology and Archaeology Specimen provenance Specimen deposition

Dating methods
Tick this box to confirm that the raw and calibrated dates are available in the paper or in Supplementary Information.

Ethics oversight
Note that full information on the approval of the study protocol must also be provided in the manuscript.

Animals and other organisms
Policy information about studies involving animals; ARRIVE guidelines recommended for reporting animal research Laboratory animals

Wild animals
Field-collected samples

Ethics oversight
Note that full information on the approval of the study protocol must also be provided in the manuscript.

Human research participants
Policy information about studies involving human research participants Population characteristics

Recruitment
Ethics oversight Note that full information on the approval of the study protocol must also be provided in the manuscript.

Clinical data Policy information about clinical studies
All manuscripts should comply with the ICMJEguidelines for publication of clinical research and a completedCONSORT checklist must be included with all submissions.

Clinical trial registration
Study protocol

Data collection
Name any commonly misidentified cell lines used in the study and provide a rationale for their use.
Provide provenance information for specimens and describe permits that were obtained for the work (including the name of the issuing authority, the date of issue, and any identifying information).
Indicate where the specimens have been deposited to permit free access by other researchers.
If new dates are provided, describe how they were obtained (e.g. collection, storage, sample pretreatment and measurement), where they were obtained (i.e. lab name), the calibration program and the protocol for quality assurance OR state that no new dates are provided.
Identify the organization(s) that approved or provided guidance on the study protocol, OR state that no ethical approval or guidance was required and explain why not.
For laboratory animals, report species, strain, sex and age OR state that the study did not involve laboratory animals.
Provide details on animals observed in or captured in the field; report species, sex and age where possible. Describe how animals were caught and transported and what happened to captive animals after the study (if killed, explain why and describe method; if released, say where and when) OR state that the study did not involve wild animals.
For laboratory work with field-collected samples, describe all relevant parameters such as housing, maintenance, temperature, photoperiod and end-of-experiment protocol OR state that the study did not involve samples collected from the field.
Identify the organization(s) that approved or provided guidance on the study protocol, OR state that no ethical approval or guidance was required and explain why not. This is a meta-analysis of several cohorts of European-origin participants from Australia, Finland, Norway, the Netherlands, the UK and the USA. Age, sex distribution and genotyping conditions were all varied, with an overview in Supplementary  Table 1 and a comprehensive description in the Supplementary Note. Recruitment was conducted either through dermatology clinics (KCL cohort) or from volunteers in population-based studies (all other cohorts). Acne diagnosis was performed using either clinical assessment, self-report questionnaires or linkage to electronic health record diagnoses -this heterogeneity in cohort definitions may introduce bias into the effect size estimates, with estimates from clinically ascertained cohorts typically larger. Volunteers in population-based studies are more likely to be health-conscious with a well established "healthy volunteer" effect -if this includes correlation with acne prevalence it may introduce bias into effect size estimates.

nature research | reporting summary
April 2020 Flow Cytometry Plots Confirm that: The axis labels state the marker and fluorochrome used (e.g. CD4-FITC).
The axis scales are clearly visible. Include numbers along axes only for bottom left plot of group (a 'group' is an analysis of identical markers).
All plots are contour plots with outliers or pseudocolor plots.
A numerical value for number of cells or percentage (with statistics) is provided.