A Genome-Wide Association Study Identifies the Skin Color Genes IRF4, MC1R, ASIP, and BNC2 Influencing Facial Pigmented Spots

被引：100

作者：

Jacobs, Leonie C. ^{[1
,2
]}

Hamer, Merel A. ^{[1
,2
]}

Gunn, David A. ^{[3
]}

Deelen, Joris ^{[2
,4
]}

Lall, Jaspal S. ^{[3
]}

van Heemst, Diana ^{[5
]}

Uh, Hae-Won ^{[6
]}

Hofman, Albert ^{[7
]}

Uitterlinden, Andre G. ^{[2
,7
,8
]}

Griffiths, Christopher E. M. ^{[9
]}

Beekman, Marian ^{[2
,4
]}

Slagboom, P. Eline ^{[2
,4
]}

Kayser, Manfred ^{[10
]}

Liu, Fan ^{[10
]}

Nijsten, Tamar ^{[1
,2
]}

机构：

[1] Erasmus MC Univ Med Ctr Rotterdam, Dept Dermatol, NL-3000 CA Rotterdam, Netherlands

[2] NCHA, Netherlands Genom Initiat NGI Sponsored, Leiden, Netherlands

[3] Unilever, R&D, Sharnbrook, Beds, England

[4] Leiden Univ Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands

[5] Leiden Univ Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands

[6] Leiden Univ Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands

[7] Erasmus MC Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands

[8] Erasmus MC Univ Med Ctr Rotterdam, Dept Internal Med, Rotterdam, Netherlands

[9] Univ Manchester, Salford Royal NHS Fdn Trust, Dermatol Ctr, Salford, Lancs, England

[10] Erasmus MC Univ Med Ctr Rotterdam, Dept Forens Mol Biol, Rotterdam, Netherlands

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2015年 / 135卷 / 07期

关键词：

SUN EXPOSURE; RISK-FACTORS; VARIANTS; CANCER; MELANOMA; DETERMINANTS; WOMEN; POLYMORPHISMS; POPULATION; LENTIGINES;

D O I：

10.1038/jid.2015.62

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Facial pigmented spots are a common skin aging feature, but genetic predisposition has yet to be thoroughly investigated. We conducted a genome-wide association study for pigmented spots in 2,844 Dutch Europeans from the Rotterdam Study (mean age: 66.9 +/- 8.0 years; 47% male). Using semi-automated image analysis of high-resolution digital facial photographs, facial pigmented spots were quantified as the percentage of affected skin area (mean women: 2.0% +/- 0.9, men: 0.9% +/- 0.6). We identified genome-wide significant association with pigmented spots at three genetic loci: IRF4 (rs12203592, P = 1.8 x 10(-27)), MC1R (compound heterozygosity score, P = 2.3 x 10(-24)), and RALY/ASIP (rs6059655, P = 1.9 x 10(-9)). In addition, after adjustment for the other three top-associated loci the BNC2 locus demonstrated significant association (rs62543565, P= 2.3 x 10(-8)). The association signals observed at all four loci were successfully replicated (P < 0.05) in an independent Dutch cohort (Leiden Longevity Study n = 599). Although the four genes have previously been associated with skin color variation and skin cancer risk, all association signals remained highly significant (P < 2 x 10(-8)) when conditioning the association analyses on skin color. We conclude that genetic variations in IRF4, MC1R, RALY/ASIP, and BNC2 contribute to the acquired amount of facial pigmented spots during aging, through pathways independent of the basal melanin production.

引用

页码：1735 / 1742

页数：8

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