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

Brittany L. Mitchell; Jake R. Saklatvala; Nick Dand; Fiona A. Hagenbeek; Xin Li; Josine L. Min; Laurent Thomas; Meike Bartels; Jouke Jan Hottenga; Michelle K. Lupton; Dorret I. Boomsma; Xianjun Dong; Kristian Hveem; Mari Løset; Nicholas G. Martin; Jonathan N. Barker; Jiali Han; Catherine H. Smith; Miguel E. Rentería; Michael A. Simpson

doi:10.1038/s41467-022-28252-5

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

Brittany L. Mitchell, Jake R. Saklatvala, Nick Dand, Fiona A. Hagenbeek, Xin Li, Josine L. Min, Laurent Thomas, Meike Bartels, Jouke Jan Hottenga, Michelle K. Lupton, Dorret I. Boomsma, Xianjun Dong, Kristian Hveem, Mari Løset, Nicholas G. Martin, Jonathan N. Barker, Jiali Han, Catherine H. Smith, Miguel E. Rentería^*, Michael A. Simpson

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	702
Pages (from-to)	1-9
Number of pages	9
Journal	Nature Communications
Volume	13
Early online date	7 Feb 2022
DOIs	https://doi.org/10.1038/s41467-022-28252-5
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
We thank the participants who donated their time, life experiences and DNA to this research, and the clinical and scientific teams that worked with them. We acknowledge support from the National Institute for Health Research (NIHR), through the NIHR Biomedical Research Centre based at Guy?s and St Thomas? NHS Foundation Trust and King?s College London. Health Data Research UK (MR/S003126/1). Acknowledgments for each cohort that contributed to this meta-analysis can be found in the supplementary information.

Funding Information:
We thank the participants who donated their time, life experiences and DNA to this research, and the clinical and scientific teams that worked with them. We acknowledge support from the National Institute for Health Research (NIHR), through the NIHR Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. Health Data Research UK (MR/S003126/1). Acknowledgments for each cohort that contributed to this meta-analysis can be found in the supplementary information.

Publisher Copyright:
© 2022, The Author(s).

Funding

We thank the participants who donated their time, life experiences and DNA to this research, and the clinical and scientific teams that worked with them. We acknowledge support from the National Institute for Health Research (NIHR), through the NIHR Biomedical Research Centre based at Guy\u2019s and St Thomas\u2019 NHS Foundation Trust and King\u2019s College London. Health Data Research UK (MR/S003126/1). Acknowledgments for each cohort that contributed to this meta-analysis can be found in the supplementary information.

Funders	Funder number
King’s College London	MR/S003126/1
Manchester Biomedical Research Centre
National Institute for Health and Care Research
Guy's and St Thomas' NHS Foundation Trust

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Mitchell, B. L., Saklatvala, J. R., Dand, N., Hagenbeek, F. A., Li, X., Min, J. L., Thomas, L., Bartels, M., Jan Hottenga, J., Lupton, M. K., Boomsma, D. I., Dong, X., Hveem, K., Løset, M., Martin, N. G., Barker, J. N., Han, J., Smith, C. H., Rentería, M. E., & Simpson, M. A. (2022). Genome-wide association meta-analysis identifies 29 new acne susceptibility loci. Nature Communications, 13, 1-9. Article 702. https://doi.org/10.1038/s41467-022-28252-5

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title = "Genome-wide association meta-analysis identifies 29 new acne susceptibility loci",

abstract = "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.",

author = "Mitchell, {Brittany L.} and Saklatvala, {Jake R.} and Nick Dand and Hagenbeek, {Fiona A.} and Xin Li and Min, {Josine L.} and Laurent Thomas and Meike Bartels and {Jan Hottenga}, Jouke and Lupton, {Michelle K.} and Boomsma, {Dorret I.} and Xianjun Dong and Kristian Hveem and Mari L{\o}set and Martin, {Nicholas G.} and Barker, {Jonathan N.} and Jiali Han and Smith, {Catherine H.} and Renter{\'i}a, {Miguel E.} and Simpson, {Michael A.}",

note = "Funding Information: We thank the participants who donated their time, life experiences and DNA to this research, and the clinical and scientific teams that worked with them. We acknowledge support from the National Institute for Health Research (NIHR), through the NIHR Biomedical Research Centre based at Guy?s and St Thomas? NHS Foundation Trust and King?s College London. Health Data Research UK (MR/S003126/1). Acknowledgments for each cohort that contributed to this meta-analysis can be found in the supplementary information. Funding Information: We thank the participants who donated their time, life experiences and DNA to this research, and the clinical and scientific teams that worked with them. We acknowledge support from the National Institute for Health Research (NIHR), through the NIHR Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London. Health Data Research UK (MR/S003126/1). Acknowledgments for each cohort that contributed to this meta-analysis can be found in the supplementary information. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-28252-5",

language = "English",

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Mitchell, BL, Saklatvala, JR, Dand, N, Hagenbeek, FA, Li, X, Min, JL, Thomas, L, Bartels, M , Jan Hottenga, J, Lupton, MK, Boomsma, DI, Dong, X, Hveem, K, Løset, M, Martin, NG, Barker, JN, Han, J, Smith, CH, Rentería, ME & Simpson, MA 2022, 'Genome-wide association meta-analysis identifies 29 new acne susceptibility loci', Nature Communications, vol. 13, 702, pp. 1-9. https://doi.org/10.1038/s41467-022-28252-5

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T1 - Genome-wide association meta-analysis identifies 29 new acne susceptibility loci

AU - Mitchell, Brittany L.

AU - Saklatvala, Jake R.

AU - Dand, Nick

AU - Hagenbeek, Fiona A.

AU - Li, Xin

AU - Min, Josine L.

AU - Thomas, Laurent

AU - Bartels, Meike

AU - Jan Hottenga, Jouke

AU - Lupton, Michelle K.

AU - Boomsma, Dorret I.

AU - Dong, Xianjun

AU - Hveem, Kristian

AU - Løset, Mari

AU - Martin, Nicholas G.

AU - Barker, Jonathan N.

AU - Han, Jiali

AU - Smith, Catherine H.

AU - Rentería, Miguel E.

AU - Simpson, Michael A.

N1 - Funding Information: We thank the participants who donated their time, life experiences and DNA to this research, and the clinical and scientific teams that worked with them. We acknowledge support from the National Institute for Health Research (NIHR), through the NIHR Biomedical Research Centre based at Guy?s and St Thomas? NHS Foundation Trust and King?s College London. Health Data Research UK (MR/S003126/1). Acknowledgments for each cohort that contributed to this meta-analysis can be found in the supplementary information. Funding Information: We thank the participants who donated their time, life experiences and DNA to this research, and the clinical and scientific teams that worked with them. We acknowledge support from the National Institute for Health Research (NIHR), through the NIHR Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. Health Data Research UK (MR/S003126/1). Acknowledgments for each cohort that contributed to this meta-analysis can be found in the supplementary information. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

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ER -

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

Abstract

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