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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).

SUBMITTER: Zhang M

PROVIDER: S-EPMC3690971 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans.

Zhang Mingfeng M Song Fengju F Liang Liming L Nan Hongmei H Zhang Jiangwen J Liu Hongliang H Wang Li-E LE Wei Qingyi Q Lee Jeffrey E JE Amos Christopher I CI Kraft Peter P Qureshi Abrar A AA Han Jiali J

Human molecular genetics 20130401 14

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 f ...[more]

PMID: 23548203

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Project description:A recent genome-wide association study (GWAS) in African descent populations identified novel loci associated with skin pigmentation. However, how genomic variations affect skin pigmentation and how these skin pigmentation gene variants affect serum 25(OH) vitamin D variation has not been explored in African Americans (AAs). In order to further understand genetic factors that affect human skin pigmentation and serum 25(OH)D variation, we performed a GWAS for skin pigmentation with 395 AAs and a replication study with 681 AAs. Then, we tested if the identified variants are associated with serum 25(OH) D concentrations in a subset of AAs (n = 591). Skin pigmentation, Melanin Index (M-Index), was measured using a narrow-band reflectometer. Multiple regression analysis was performed to identify variants associated with M-Index and to assess their role in serum 25(OH)D variation adjusting for population stratification and relevant confounding variables. A variant near the SLC24A5 gene (rs2675345) showed the strongest signal of association with M-Index (P = 4.0 x 10-30 in the pooled dataset). Variants in SLC24A5, SLC45A2 and OCA2 together account for a large proportion of skin pigmentation variance (11%). The effects of these variants on M-Index was modified by sex (P for interaction = 0.009). However, West African Ancestry (WAA) also accounts for a large proportion of M-Index variance (23%). M-Index also varies among AAs with high WAA and high Genetic Score calculated from top variants associated with M-Index, suggesting that other unknown genomic factors related to WAA are likely contributing to skin pigmentation variation. M-Index was not associated with serum 25(OH)D concentrations, but the Genetic Score was significantly associated with vitamin D deficiency (serum 25(OH)D levels less than 12 ng/mL) (OR, 1.30; 95% CI, 1.04-1.64). The findings support the hypothesis suggesting that skin pigmentation evolved responding to increased demand for subcutaneous vitamin D synthesis in high latitude environments.

Dataset Information

Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans.

Publications

Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans.

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