title: Identification of a novel locus associated with skin colour in African-admixed populations.
abstract: Skin pigmentation is a complex trait that varies largely among populations. Most genome-wide association studies of this trait have been performed in Europeans and Asians. We aimed to uncover genes influencing skin colour in African-admixed individuals. We performed a genome-wide association study of melanin levels in 285 Hispanic/Latino individuals from Puerto Rico, analyzing 14 million genetic variants. A total of 82 variants with p-value ≤1 × 10-5were followed up in 373 African Americans. Fourteen single nucleotide polymorphisms were replicated, of which nine were associated with skin colour at genome-wide significance in a meta-analysis across the two studies. These results validated the association of two previously known skin pigmentation genes, SLC24A5 (minimum p = 2.62 × 10-14, rs1426654) and SLC45A2 (minimum p = 9.71 × 10-10, rs16891982), and revealed the intergenic region of BEND7 and PRPF18 as a novel locus associated with this trait (minimum p = 4.58 × 10-9, rs6602666). The most significant variant within this region is common among African-descent populations but not among Europeans or Native Americans. Our findings support the advantages of analyzing African-admixed populations to discover new genes influencing skin pigmentation.
authors.affiliation: Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.|Applied Genomics Group (G2A), Section of Genetics, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, San Cristobal de La Laguna, Tenerife, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Hernandez-Pacheco
authors.affiliation: Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.|CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Flores
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, Leioa, Bizkaia, Spain.
authors.forename: Santos
authors.initials: S
authors.lastname: Alonso
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, United States.
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, United States.
authors.forename: Angel C Y
authors.initials: AC
authors.lastname: Mak
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: Hunstman
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, United States.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, United States.
authors.forename: Marquitta J
authors.initials: MJ
authors.lastname: White
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, United States.
authors.forename: Sam S
authors.initials: SS
authors.lastname: Oh
authors.affiliation: Children's Hospital and Research Center Oakland, Oakland, CA, USA.
authors.forename: Kelley
authors.initials: K
authors.lastname: Meade
authors.affiliation: Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Farber
authors.affiliation: Allergy &ENT Associates, Woodlands, TX, USA.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.affiliation: Pediatric Pulmonary Division, Jacobi Medical Center, Bronx, NY, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Serebrisky
authors.affiliation: Department of Pediatrics, University of California San Francisco, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Thyne
authors.affiliation: Department of Allergy and Immunology, Kaiser Permanente-Vallejo Medical Center, Vallejo, CA, USA.
authors.forename: Emerita
authors.initials: E
authors.lastname: Brigino-Buenaventura
authors.affiliation: Veterans Caribbean Health Care System, San Juan, Puerto Rico.
authors.forename: William
authors.initials: W
authors.lastname: Rodriguez-Cintron
authors.affiliation: Division of Biostatistics, Department of Preventive Medicine, UTHSC, Memphis, TN, USA.
authors.forename: Saunak
authors.initials: S
authors.lastname: Sen
authors.affiliation: Children's Memorial Hospital and the Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Bay Area Pediatrics, Oakland, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lenoir
authors.affiliation: Centro de Neumología Pediátrica, San Juan, Puerto Rico.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Rodriguez-Santana
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, United States.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, United States.
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.affiliation: Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.|CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Pino-Yanes
mesh_terms: D001741:Black or African American / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics*; D017920:Antiporters / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D021901:DNA, Intergenic / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D000072260:RNA Splicing Factors / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics* / Q000502:physiology; D044465:White People / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D017920:Antiporters; C000628965:BEND7 protein, human; D021901:DNA, Intergenic; D026901:Membrane Transport Proteins; C448981:PRPF18 protein, human; D011506:Proteins; D000072260:RNA Splicing Factors; C506584:SLC24A5 protein, human; C510061:SLC45A2 protein, human