Title
A genome-wide association study identifies novel gene associations with facial skin wrinkling and mole count in Latin Americans
Date Issued
01 November 2021
Access level
open access
Resource Type
journal article
Author(s)
Chen Y.
André M.
Adhikari K.
Blin M.
Bonfante B.
Fuentes-Guajardo M.
Palmal S.
Chacón-Duque J.C.
Hurtado M.
Granja V.
Jaramillo C.
Arias W.
Lozano R.B.
Everardo-Martínez P.
Gómez-Valdés J.
Villamil-Ramírez H.
de Cerqueira C.C.S.
Hünemeier T.
Ramallo V.
Gonzalez-José R.
Schüler-Faccini L.
Bortolini M.C.
Acuña-Alonzo V.
Canizales-Quinteros S.
Bedoya G.
Rothhammer F.
Balding D.
Tobin D.J.
Wang S.
Faux P.
Ruiz-Linares A.
Publisher(s)
John Wiley and Sons Inc
Abstract
Background: Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans. Objectives: To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America. Methods: Skin ageing and mole count scores were obtained from facial photographs of over 6000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina’s HumanOmniExpress chip. Association testing was performed on around 8 703 729 single-nucleotide polymorphisms (SNPs) across the autosomal genome. Results: Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13·3 and 21q21·2), one with mole count (in 1q32·3) and one with both wrinkling and mole count (in 5p13·2). Associated SNPs in 5p13·2 and in 1p13·3 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32·3 are near the SLC30A1 gene, and those in 21q21·2 occur in a gene desert. Analyses of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing. Conclusions: We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.
Start page
988
End page
998
Volume
185
Issue
5
Language
English
OCDE Knowledge area
Genética humana
Scopus EID
2-s2.0-85118522722
PubMed ID
Source
British Journal of Dermatology
ISSN of the container
00070963
Sponsor(s)
sources Work leading to this publication received funding from the National Natural Science Foundation of China (#31771393), the Scientific and Technology Committee of Shanghai Municipality (18490750300), the Ministry of Science and Technology of China (2020YFE0201600), Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the 111 Project (B13016), the Leverhulme Trust (F/07 134/DF), BBSRC (BB/I021213/1), the Excellence Initiative of Aix-Marseille University – A*MIDEX (a French ‘Investissements d’Avenir’ programme), Universidad de Antioquia (CODI sostenibilidad de grupos 2013-2014 and MASO 2013-2014), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Apoio a Núcleos de Excelência Program) and Fundação de Aperfeiçoamento de Pessoal de Nível Superior. B.B. is supported by a doctoral scholarship from Ecole Doctorale 251 Aix-Marseille Université.We thank the volunteers for their enthusiastic support for this research. We also thank Alvaro Alvarado, Mónica Ballesteros Romero, Ricardo Cebrecos, Miguel Ángel Contreras Sieck, Francisco de Ávila Becerril, Joyce De la Piedra, María Teresa Del Solar, William Flores, Martha Granados Riveros, Rosilene Paim, Ricardo Gunski, Sergeant João Felisberto Menezes Cavalheiro, Major Eugênio Correa de Souza Junior, Wendy Hart, Ilich Jafet Moreno, Paola León-Mimila, Francisco Quispealaya, Diana Rogel Diaz, Ruth Rojas and Vanessa Sarabia, for assistance with volunteer recruitment, sample processing and data entry. We are very grateful to the institutions that allowed the use of their facilities for the assessment of volunteers, including Escuela Nacional de Antropología e Historia and Universidad Nacional Autónoma de México (México); Universidade Federal do Rio Grande do Sul (Brazil); 13° Companhia de Comunicações Mecanizada do Exército Brasileiro (Brazil); and Pontificia Universidad Católica del Perú, Universidad de Lima and Universidad Nacional Mayor de San Marcos (Perú). We acknowledge the Centre de Calcul Intensif d’Aix-Marseille for granting access to high-performance computing resources. We thank Nick Martin, Matthew Law and David Duffy for helpful discussions.
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