title: OPRM1 and EGFR contribute to skin pigmentation differences between Indigenous Americans and Europeans.
abstract: Contemporary variation in skin pigmentation is the result of hundreds of thousands years of human evolution in new and changing environments. Previous studies have identified several genes involved in skin pigmentation differences among African, Asian, and European populations. However, none have examined skin pigmentation variation among Indigenous American populations, creating a critical gap in our understanding of skin pigmentation variation. This study investigates signatures of selection at 76 pigmentation candidate genes that may contribute to skin pigmentation differences between Indigenous Americans and Europeans. Analysis was performed on two samples of Indigenous Americans genotyped on genome-wide SNP arrays. Using four tests for natural selection--locus-specific branch length (LSBL), ratio of heterozygosities (lnRH), Tajima's D difference, and extended haplotype homozygosity (EHH)--we identified 14 selection-nominated candidate genes (SNCGs). SNPs in each of the SNCGs were tested for association with skin pigmentation in 515 admixed Indigenous American and European individuals from regions of the Americas with high ground-level ultraviolet radiation. In addition to SLC24A5 and SLC45A2, genes previously associated with European/non-European differences in skin pigmentation, OPRM1 and EGFR were associated with variation in skin pigmentation in New World populations for the first time.
authors.affiliation: Department of Anthropology, Pennsylvania State University, University Park, PA 16802, USA. equillen@txbiomedgenetics.org
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Quillen
authors.forename: Marc
authors.initials: M
authors.lastname: Bauchet
authors.forename: Abigail W
authors.initials: AW
authors.lastname: Bigham
authors.forename: Miguel E
authors.initials: ME
authors.lastname: Delgado-Burbano
authors.forename: Franz X
authors.initials: FX
authors.lastname: Faust
authors.forename: Yann C
authors.initials: YC
authors.lastname: Klimentidis
authors.forename: Xianyun
authors.initials: X
authors.lastname: Mao
authors.forename: Mark
authors.initials: M
authors.lastname: Stoneking
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics; D017920:Antiporters / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; D017920:Antiporters; D026901:Membrane Transport Proteins; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; C506584:SLC24A5 protein, human; C510061:SLC45A2 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors