title: Genetics of skin color variation in Europeans: genome-wide association studies with functional follow-up.
abstract: In the International Visible Trait Genetics (VisiGen) Consortium, we investigated the genetics of human skin color by combining a series of genome-wide association studies (GWAS) in a total of 17,262 Europeans with functional follow-up of discovered loci. Our GWAS provide the first genome-wide significant evidence for chromosome 20q11.22 harboring the ASIP gene being explicitly associated with skin color in Europeans. In addition, genomic loci at 5p13.2 (SLC45A2), 6p25.3 (IRF4), 15q13.1 (HERC2/OCA2), and 16q24.3 (MC1R) were confirmed to be involved in skin coloration in Europeans. In follow-up gene expression and regulation studies of 22 genes in 20q11.22, we highlighted two novel genes EIF2S2 and GSS, serving as competing functional candidates in this region and providing future research lines. A genetically inferred skin color score obtained from the 9 top-associated SNPs from 9 genes in 940 worldwide samples (HGDP-CEPH) showed a clear gradual pattern in Western Eurasians similar to the distribution of physical skin color, suggesting the used 9 SNPs as suitable markers for DNA prediction of skin color in Europeans and neighboring populations, relevant in future forensic and anthropological investigations.
authors.affiliation: Department of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands, f.liu@erasmusmc.nl.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.forename: Mijke
authors.initials: M
authors.lastname: Visser
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.forename: Pirro G
authors.initials: PG
authors.lastname: Hysi
authors.forename: Leonie C
authors.initials: LC
authors.lastname: Jacobs
authors.forename: Oscar
authors.initials: O
authors.lastname: Lao
authors.forename: Kaiyin
authors.initials: K
authors.lastname: Zhong
authors.forename: Susan
authors.initials: S
authors.lastname: Walsh
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Chaitanya
authors.forename: Andreas
authors.initials: A
authors.lastname: Wollstein
authors.forename: Gu
authors.initials: G
authors.lastname: Zhu
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Anjali K
authors.initials: AK
authors.lastname: Henders
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.forename: Daniel
authors.initials: D
authors.lastname: Glass
authors.forename: Veronique
authors.initials: V
authors.lastname: Bataille
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sturm
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Wilfred F J
authors.initials: WF
authors.lastname: van IJcken
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Robert-Jan T S
authors.initials: RJ
authors.lastname: Palstra
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Tamar E C
authors.initials: TE
authors.lastname: Nijsten
authors.forename: Manfred
authors.initials: M
authors.lastname: Kayser
mesh_terms: D054366:Agouti Signaling Protein / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012880:Skin Pigmentation / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases; D006113:United Kingdom; D044465:White People / Q000235:genetics*; D000099218:Interferon Regulatory Factor-4
chemical_list: D054366:Agouti Signaling Protein; D000951:Antigens, Neoplasm; D020662:Guanine Nucleotide Exchange Factors; D050835:Interferon Regulatory Factors; D026901:Membrane Transport Proteins; D044767:Ubiquitin-Protein Ligases; D000099218:Interferon Regulatory Factor-4; C515182:ASIP protein, human; C510061:SLC45A2 protein, human; C118566:HERC2 protein, human