title: Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans.
abstract: Aiming to identify novel genetic loci for pigmentation and skin cancer, we conducted a series of genome-wide association studies on hair color, eye color, number of sunburns, tanning ability and number of non-melanoma skin cancers (NMSCs) among 10 183 European Americans in the discovery stage and 4504 European Americans in the replication stage (for eye color, 3871 males in the discovery stage and 2496 males in the replication stage). We targeted novel chromosome regions besides the known ones for replication. As a result, we identified a new region downstream of the EDNRB gene on 13q22 associated with hair color and the strongest association was the single-nucleotide polymorphism (SNP) rs975739 (P = 2.4 × 10(-14); P = 5.4 × 10(-9) in the discovery set and P = 1.2 × 10(-6) in the replication set). Using blue, intermediate (including green) and brown eye colors as co-dominant outcomes, we identified the SNP rs3002288 in VASH2 on 1q32.3 associated with brown eye (P = 7.0 × 10(-8); P = 5.3 × 10(-5) in the discovery set and P = 0.02 in the replication set). Additionally, we identified a significant interaction between the SNPs rs7173419 and rs12913832 in the OCA2 gene region on brown eye color (P-value for interaction = 3.8 × 10(-3)). As for the number of NMSCs, we identified two independent SNPs on chr6 and one SNP on chromosome 14: rs12203592 in IRF4 (P = 7.2 × 10(-14); P = 1.8 × 10(-8) in the discovery set and P = 6.7 × 10(-7) in the replication set), rs12202284 between IRF4 and EXOC2 (P = 5.0 × 10(-8); P = 6.6 × 10(-7) in the discovery set and P = 3.0 × 10(-3) in the replication set) and rs8015138 upstream of GNG2 (P = 6.6 × 10(-8); P = 5.3 × 10(-7) in the discovery set and P = 0.01 in the replication set).
authors.affiliation: Clinical Research Program, Department of Dermatology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Fengju
authors.initials: F
authors.lastname: Song
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Nan
authors.forename: Jiangwen
authors.initials: J
authors.lastname: Zhang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics; D016022:Case-Control Studies; D005127:Eye Color; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012878:Skin Neoplasms / Q000208:ethnology / Q000235:genetics*; D012880:Skin Pigmentation; D044465:White People / Q000235:genetics*; D000099218:Interferon Regulatory Factor-4
chemical_list: D042501:Angiogenic Proteins; D019204:GTP-Binding Proteins; D050835:Interferon Regulatory Factors; D026901:Membrane Transport Proteins; D000099218:Interferon Regulatory Factor-4; C410342:GNG2 protein, human; C489600:OCA2 protein, human; C574858:VASH2 protein, human
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