Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer

Bonilla, Carolina - Bertoni, Bernardo - Min, Josine L. - Hemani, Gibran - Elliott, Hannah R. - Genetics of DNA Methylation Consortium

Resumen:

Pigmentation characteristics are well-known risk factors for skin cancer. Polymorphisms in pigmentation genes have been associated with these traits and with the risk of malignancy. However, the functional relationship between genetic variation and disease is still unclear. This study aims to assess whether pigmentation SNPs are associated with pigmentary traits and skin cancer via DNA methylation (DNAm). Using a meta-GWAS of whole-blood DNAm from 36 European cohorts (N = 27,750; the Genetics of DNA Methylation Consortium, GoDMC), we found that 19 out of 27 SNPs in 10 pigmentation genes were associated with 391 DNAm sites across 30 genomic regions. We examined the effect of 25 selected DNAm sites on pigmentation traits, sun exposure phenotypes and skin cancer and on gene expression in whole blood. We uncovered an association of DNAm site cg07402062 with red hair in the Avon Longitudinal Study of Parents and Children (ALSPAC). We also found that the expression of ASIP and CDK10 was associated with hair colour, melanoma and basal cell carcinoma. Our results indicate that DNAm and expression of pigmentation genes may play a role as potential mediators of the relationship between genetic variants, pigmentation phenotypes and skin cancer and thus deserve further scrutiny.

Detalles Bibliográficos
2021
ASIP
MC1R
ALSPAC
DNA methylation
GoDMC
Pigmentation
Skin cancer
PROTEÍNA DE SEÑALIZACIÓN AGOUTI
GENÉTICA
METABOLISMO
CARCINOMA BASOCELULAR
NEOPLASIAS CUTÁNEAS
QUINASAS CICLINA-DEPENDIENTES
METILACIÓN DE ADN
HUMANOS
ESTUDIO DE ASOCIACIÓN DEL GENOMA COMPLETO
ADN DE NEOPLASIAS
MELANOMA
ESTUDIOS LONGITUDINALES
PROTEÍNAS DE NEOPLASIAS
PIGMENTACIÓN DE LA PIEL
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/55444
Acceso abierto
Licencia Creative Commons Atribución (CC - By 4.0)
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author Bonilla, Carolina
author2 Bertoni, Bernardo
Min, Josine L.
Hemani, Gibran
Elliott, Hannah R.
Genetics of DNA Methylation Consortium
author2_role author
author
author
author
author
author_facet Bonilla, Carolina
Bertoni, Bernardo
Min, Josine L.
Hemani, Gibran
Elliott, Hannah R.
Genetics of DNA Methylation Consortium
author_role author
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collection COLIBRI
dc.contributor.filiacion.none.fl_str_mv Bonilla Carolina, Universidade de São Paulo (Brasil). Faculdade de Medicina. Departamento de Medicina Preventiva; University of Bristol (E.E.U.U.). Bristol Medical School. Population Health Sciences
Bertoni Bernardo, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Genética
Min Josine L., University of Bristol (E.E.U.U.). Bristol Medical School. Population Health Sciences and MRC Integrative Epidemiology Unit
Hemani Gibran, University of Bristol (E.E.U.U.). Bristol Medical School. Population Health Sciences and MRC Integrative Epidemiology Unit
Elliott Hannah R., University of Bristol (E.E.U.U.). Bristol Medical School. Population Health Sciences and MRC Integrative Epidemiology Unit
Genetics of DNA Methylation Consortium, Autor corporativo
dc.creator.none.fl_str_mv Bonilla, Carolina
Bertoni, Bernardo
Min, Josine L.
Hemani, Gibran
Elliott, Hannah R.
Genetics of DNA Methylation Consortium
dc.date.accessioned.none.fl_str_mv 2026-06-11T12:41:49Z
dc.date.available.none.fl_str_mv 2026-06-11T12:41:49Z
dc.date.issued.none.fl_str_mv 2021
dc.description.abstract.none.fl_txt_mv Pigmentation characteristics are well-known risk factors for skin cancer. Polymorphisms in pigmentation genes have been associated with these traits and with the risk of malignancy. However, the functional relationship between genetic variation and disease is still unclear. This study aims to assess whether pigmentation SNPs are associated with pigmentary traits and skin cancer via DNA methylation (DNAm). Using a meta-GWAS of whole-blood DNAm from 36 European cohorts (N = 27,750; the Genetics of DNA Methylation Consortium, GoDMC), we found that 19 out of 27 SNPs in 10 pigmentation genes were associated with 391 DNAm sites across 30 genomic regions. We examined the effect of 25 selected DNAm sites on pigmentation traits, sun exposure phenotypes and skin cancer and on gene expression in whole blood. We uncovered an association of DNAm site cg07402062 with red hair in the Avon Longitudinal Study of Parents and Children (ALSPAC). We also found that the expression of ASIP and CDK10 was associated with hair colour, melanoma and basal cell carcinoma. Our results indicate that DNAm and expression of pigmentation genes may play a role as potential mediators of the relationship between genetic variants, pigmentation phenotypes and skin cancer and thus deserve further scrutiny.
dc.format.extent.es.fl_str_mv 13 p.
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dc.identifier.citation.es.fl_str_mv Bonilla C, Bertoni B, Min J y otros. Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer. Pigment Cell and Melanoma Research [en línea]. 2021;34(5):892-904
dc.identifier.doi.none.fl_str_mv 10.1111/pcmr.12948
dc.identifier.eissn.none.fl_str_mv 1755-148X
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12008/55444
dc.language.iso.none.fl_str_mv en
eng
dc.publisher.es.fl_str_mv Wiley
dc.relation.none.fl_str_mv Pigment Cell and Melanoma Research. 2021;34(5):892-904
dc.rights.license.none.fl_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.es.fl_str_mv ASIP
MC1R
ALSPAC
DNA methylation
GoDMC
Pigmentation
Skin cancer
dc.subject.other.es.fl_str_mv PROTEÍNA DE SEÑALIZACIÓN AGOUTI
GENÉTICA
METABOLISMO
CARCINOMA BASOCELULAR
NEOPLASIAS CUTÁNEAS
QUINASAS CICLINA-DEPENDIENTES
METILACIÓN DE ADN
HUMANOS
ESTUDIO DE ASOCIACIÓN DEL GENOMA COMPLETO
ADN DE NEOPLASIAS
MELANOMA
ESTUDIOS LONGITUDINALES
PROTEÍNAS DE NEOPLASIAS
PIGMENTACIÓN DE LA PIEL
dc.title.none.fl_str_mv Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer
dc.type.es.fl_str_mv Artículo
dc.type.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
description Pigmentation characteristics are well-known risk factors for skin cancer. Polymorphisms in pigmentation genes have been associated with these traits and with the risk of malignancy. However, the functional relationship between genetic variation and disease is still unclear. This study aims to assess whether pigmentation SNPs are associated with pigmentary traits and skin cancer via DNA methylation (DNAm). Using a meta-GWAS of whole-blood DNAm from 36 European cohorts (N = 27,750; the Genetics of DNA Methylation Consortium, GoDMC), we found that 19 out of 27 SNPs in 10 pigmentation genes were associated with 391 DNAm sites across 30 genomic regions. We examined the effect of 25 selected DNAm sites on pigmentation traits, sun exposure phenotypes and skin cancer and on gene expression in whole blood. We uncovered an association of DNAm site cg07402062 with red hair in the Avon Longitudinal Study of Parents and Children (ALSPAC). We also found that the expression of ASIP and CDK10 was associated with hair colour, melanoma and basal cell carcinoma. Our results indicate that DNAm and expression of pigmentation genes may play a role as potential mediators of the relationship between genetic variants, pigmentation phenotypes and skin cancer and thus deserve further scrutiny.
eu_rights_str_mv openAccess
format article
id COLIBRI_ae1a9d7a46da286fba6916e3f54c50b9
identifier_str_mv Bonilla C, Bertoni B, Min J y otros. Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer. Pigment Cell and Melanoma Research [en línea]. 2021;34(5):892-904
10.1111/pcmr.12948
1755-148X
instacron_str Universidad de la República
institution Universidad de la República
instname_str Universidad de la República
language eng
language_invalid_str_mv en
network_acronym_str COLIBRI
network_name_str COLIBRI
oai_identifier_str oai:colibri.udelar.edu.uy:20.500.12008/55444
publishDate 2021
reponame_str COLIBRI
repository.mail.fl_str_mv karina.camps@seciu.edu.uy
repository.name.fl_str_mv COLIBRI - Universidad de la República
repository_id_str 4771
rights_invalid_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
spelling Bonilla Carolina, Universidade de São Paulo (Brasil). Faculdade de Medicina. Departamento de Medicina Preventiva; University of Bristol (E.E.U.U.). Bristol Medical School. Population Health SciencesBertoni Bernardo, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de GenéticaMin Josine L., University of Bristol (E.E.U.U.). Bristol Medical School. Population Health Sciences and MRC Integrative Epidemiology UnitHemani Gibran, University of Bristol (E.E.U.U.). Bristol Medical School. Population Health Sciences and MRC Integrative Epidemiology UnitElliott Hannah R., University of Bristol (E.E.U.U.). Bristol Medical School. Population Health Sciences and MRC Integrative Epidemiology UnitGenetics of DNA Methylation Consortium, Autor corporativo2026-06-11T12:41:49Z2026-06-11T12:41:49Z2021Bonilla C, Bertoni B, Min J y otros. Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer. Pigment Cell and Melanoma Research [en línea]. 2021;34(5):892-904https://hdl.handle.net/20.500.12008/5544410.1111/pcmr.129481755-148XPigmentation characteristics are well-known risk factors for skin cancer. Polymorphisms in pigmentation genes have been associated with these traits and with the risk of malignancy. However, the functional relationship between genetic variation and disease is still unclear. This study aims to assess whether pigmentation SNPs are associated with pigmentary traits and skin cancer via DNA methylation (DNAm). Using a meta-GWAS of whole-blood DNAm from 36 European cohorts (N = 27,750; the Genetics of DNA Methylation Consortium, GoDMC), we found that 19 out of 27 SNPs in 10 pigmentation genes were associated with 391 DNAm sites across 30 genomic regions. We examined the effect of 25 selected DNAm sites on pigmentation traits, sun exposure phenotypes and skin cancer and on gene expression in whole blood. We uncovered an association of DNAm site cg07402062 with red hair in the Avon Longitudinal Study of Parents and Children (ALSPAC). We also found that the expression of ASIP and CDK10 was associated with hair colour, melanoma and basal cell carcinoma. Our results indicate that DNAm and expression of pigmentation genes may play a role as potential mediators of the relationship between genetic variants, pigmentation phenotypes and skin cancer and thus deserve further scrutiny.Submitted by Almiñana María Cecilia (marialminana@gmail.com) on 2026-06-09T16:39:42Z No. of bitstreams: 2 license_rdf: 25630 bytes, checksum: e7132498e7c1fe99f7096667baa99b25 (MD5) Investigating DNA methylation as a potential mediator between pigmentation genes.pdf: 11522762 bytes, checksum: 093caca4a034ad2c21c0d1b5a811a1ff (MD5)Approved for entry into archive by Almiñana María Cecilia (marialminana@gmail.com) on 2026-06-09T18:30:07Z (GMT) No. of bitstreams: 2 license_rdf: 25630 bytes, checksum: e7132498e7c1fe99f7096667baa99b25 (MD5) Investigating DNA methylation as a potential mediator between pigmentation genes.pdf: 11522762 bytes, checksum: 093caca4a034ad2c21c0d1b5a811a1ff (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@seciu.edu.uy) on 2026-06-11T12:41:49Z (GMT). No. of bitstreams: 2 license_rdf: 25630 bytes, checksum: e7132498e7c1fe99f7096667baa99b25 (MD5) Investigating DNA methylation as a potential mediator between pigmentation genes.pdf: 11522762 bytes, checksum: 093caca4a034ad2c21c0d1b5a811a1ff (MD5) Previous issue date: 202113 p.application/pdfenengWileyPigment Cell and Melanoma Research. 2021;34(5):892-904Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)ASIPMC1RALSPACDNA methylationGoDMCPigmentationSkin cancerPROTEÍNA DE SEÑALIZACIÓN AGOUTIGENÉTICAMETABOLISMOCARCINOMA BASOCELULARNEOPLASIAS CUTÁNEASQUINASAS CICLINA-DEPENDIENTESMETILACIÓN DE ADNHUMANOSESTUDIO DE ASOCIACIÓN DEL GENOMA COMPLETOADN DE NEOPLASIASMELANOMAESTUDIOS LONGITUDINALESPROTEÍNAS DE NEOPLASIASPIGMENTACIÓN DE LA PIELInvestigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancerArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaBonilla, CarolinaBertoni, BernardoMin, Josine L.Hemani, GibranElliott, Hannah R.Genetics of DNA Methylation ConsortiumLICENSElicense.txtlicense.txttext/plain; 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- Universidad de la Repúblicafalse
spellingShingle Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer
Bonilla, Carolina
ASIP
MC1R
ALSPAC
DNA methylation
GoDMC
Pigmentation
Skin cancer
PROTEÍNA DE SEÑALIZACIÓN AGOUTI
GENÉTICA
METABOLISMO
CARCINOMA BASOCELULAR
NEOPLASIAS CUTÁNEAS
QUINASAS CICLINA-DEPENDIENTES
METILACIÓN DE ADN
HUMANOS
ESTUDIO DE ASOCIACIÓN DEL GENOMA COMPLETO
ADN DE NEOPLASIAS
MELANOMA
ESTUDIOS LONGITUDINALES
PROTEÍNAS DE NEOPLASIAS
PIGMENTACIÓN DE LA PIEL
status_str publishedVersion
title Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer
title_full Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer
title_fullStr Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer
title_full_unstemmed Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer
title_short Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer
title_sort Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer
topic ASIP
MC1R
ALSPAC
DNA methylation
GoDMC
Pigmentation
Skin cancer
PROTEÍNA DE SEÑALIZACIÓN AGOUTI
GENÉTICA
METABOLISMO
CARCINOMA BASOCELULAR
NEOPLASIAS CUTÁNEAS
QUINASAS CICLINA-DEPENDIENTES
METILACIÓN DE ADN
HUMANOS
ESTUDIO DE ASOCIACIÓN DEL GENOMA COMPLETO
ADN DE NEOPLASIAS
MELANOMA
ESTUDIOS LONGITUDINALES
PROTEÍNAS DE NEOPLASIAS
PIGMENTACIÓN DE LA PIEL
url https://hdl.handle.net/20.500.12008/55444

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