Abstract

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.

Pigmentation variation in humans is influenced by complex genetic architecture in different populations. Here, the authors perform a genome-wide association analysis involving > 6,000 Latin Americans for pigmentation of skin and eyes, and identify known and novel genetic associations.

Details

Title
A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia
Author
Adhikari Kaustubh 1 ; Mendoza-Revilla, Javier 2 ; Anood, Sohail 3 ; Fuentes-Guajardo, Macarena 4 ; Lampert, Jodie 5 ; Chacón-Duque, Juan Camilo 1   VIAFID ORCID Logo  ; Hurtado Malena 6 ; Villegas, Valeria 6 ; Granja Vanessa 6 ; Acuña-Alonzo, Victor 7 ; Jaramillo, Claudia 8 ; Arias, William 8 ; Lozano Rodrigo Barquera 9 ; Everardo Paola 10 ; Gómez-Valdés, Jorge 10 ; Villamil-Ramírez, Hugo 11 ; Silva de Cerqueira Caio C 12 ; Tábita, Hunemeier 12 ; Ramallo Virginia 13 ; Schuler-Faccini Lavinia 12 ; Salzano, Francisco M 12 ; Gonzalez-José, Rolando 14 ; Maria-Cátira, Bortolini 12 ; Canizales-Quinteros Samuel 11 ; Gallo, Carla 6 ; Poletti Giovanni 6 ; Bedoya, Gabriel 8 ; Rothhammer Francisco 15 ; Tobin, Desmond J 16   VIAFID ORCID Logo  ; Fumagalli Matteo 17 ; Balding, David 18 ; Ruiz-Linares, Andrés 19 

1  University College London, Department of Genetics, Evolution and Environment, and UCL Genetics Institute, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201) 
2  University College London, Department of Genetics, Evolution and Environment, and UCL Genetics Institute, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); Universidad Peruana Cayetano Heredia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Lima, Peru (GRID:grid.11100.31) (ISNI:0000 0001 0673 9488) 
3  Cambridge University, Department of Genetics, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
4  University College London, Department of Genetics, Evolution and Environment, and UCL Genetics Institute, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); Universidad de Tarapacá, Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Arica, Chile (GRID:grid.412182.c) (ISNI:0000 0001 2179 0636) 
5  University of Leicester, Department of Genetics and Genome Biology, Leicester, UK (GRID:grid.9918.9) (ISNI:0000 0004 1936 8411) 
6  Universidad Peruana Cayetano Heredia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Lima, Peru (GRID:grid.11100.31) (ISNI:0000 0001 0673 9488) 
7  University College London, Department of Genetics, Evolution and Environment, and UCL Genetics Institute, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); National Institute of Anthropology and History, Mexico City, Mexico (GRID:grid.462439.e) (ISNI:0000 0001 2169 9197) 
8  Universidad de Antioquia, GENMOL (Genética Molecular), Medellín, Colombia (GRID:grid.412881.6) (ISNI:0000 0000 8882 5269) 
9  National Institute of Anthropology and History, Mexico City, Mexico (GRID:grid.462439.e) (ISNI:0000 0001 2169 9197); Max Planck Institute for the Science of Human History, Department of Archaeogenetics, Jena, Germany (GRID:grid.469873.7) (ISNI:0000 0004 4914 1197) 
10  National Institute of Anthropology and History, Mexico City, Mexico (GRID:grid.462439.e) (ISNI:0000 0001 2169 9197) 
11  UNAM-Instituto Nacional de Medicina Genómica, Unidad de Genomica de Poblaciones Aplicada a la Salud, Facultad de Química, Mexico City, Mexico (GRID:grid.452651.1) (ISNI:0000 0004 0627 7633) 
12  Universidade Federal do Rio Grande do Sul, Departamento de Genética, Porto Alegre, Brazil (GRID:grid.8532.c) (ISNI:0000 0001 2200 7498) 
13  Universidade Federal do Rio Grande do Sul, Departamento de Genética, Porto Alegre, Brazil (GRID:grid.8532.c) (ISNI:0000 0001 2200 7498); CONICET, Instituto Patagonico de Ciencias Sociales y Humanas, Centro Nacional Patagonico, Puerto Madryn, Argentina (GRID:grid.423606.5) (ISNI:0000 0001 1945 2152) 
14  CONICET, Instituto Patagonico de Ciencias Sociales y Humanas, Centro Nacional Patagonico, Puerto Madryn, Argentina (GRID:grid.423606.5) (ISNI:0000 0001 1945 2152) 
15  Universidad de Tarapaca, Instituto de Alta Investigación, Arica, Chile (GRID:grid.412182.c) (ISNI:0000 0001 2179 0636); Universidad de Chile, Programa de Genetica Humana, ICBM, Facultad de Medicina, Santiago, Chile (GRID:grid.443909.3) (ISNI:0000 0004 0385 4466) 
16  University of Bradford, Centre for Skin Sciences, Faculty of Life Sciences, Bradford, UK (GRID:grid.6268.a) (ISNI:0000 0004 0379 5283); University College Dublin, The Charles Institute of Dermatology, Dublin, Ireland (GRID:grid.7886.1) (ISNI:0000 0001 0768 2743) 
17  Imperial College London, Department of Life Sciences, Silwood Park campus, Ascot, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
18  University College London, Department of Genetics, Evolution and Environment, and UCL Genetics Institute, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); University of Melbourne, Melbourne Integrative Genomics, Schools of BioSciences and Mathematics & Statistics, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
19  Fudan University, Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Aix-Marseille Université, CNRS, EFS, ADES, Marseille, France (GRID:grid.5399.6) (ISNI:0000 0001 2176 4817) 
Publication year
2019
Publication date
Jan 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-08147-0
ProQuest document ID
1915330822
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.