Genome-Wide Association Shows that Pigmentation Genes Play a Role in Skin Aging
Genome-Wide Association Shows that Pigmentation Genes Play a Role in Skin Aging
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DOI：
10.1016/j.jid.2017.04.026
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发表时间：
2017-09-01
影响因子：
6.5
通讯作者：
MacGregor, Stuart
中科院分区：
文献类型：
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作者：
Law, Matthew H.;Medland, Sarah E.;MacGregor, Stuart
失去精细的皮肤图案是老化和光老化的标志。研究皮肤图案的遗传贡献提供了一个机会，以更好地了解一个性状，影响物理外观和角质形成细胞皮肤癌的风险。我们对来自三个独立队列的1，671对双胞胎和1，745名单胞胎（N = 5，087）的皮肤模式（微地形评分）损伤测量的全基因组关联研究进行了荟萃分析。我们发现SLC 45 A2附近的rs 185146与皮肤衰老性状在全基因组显著性上相关（P = 4.1 x 10（-9））;据我们所知，这是以前未报道的。我们还确认了先前鉴定的位点，IRF 4附近的rs 12203592（P = 8.8 x 10（-13））和MC 1 R附近的rs 4268748（P = 1.2 x 10（-15））。在所有这三个位点，我们强调推定的功能相关的SNP。有许多红头发/低色素沉着的MC 1 R等位基因;我们发现，这些MC 1 R等位基因一起解释了4.1%的变异，在皮肤图案损伤。我们还表明，皮肤老化和报告的经验，晒伤的程度成正比的红头发的等位基因MC 1 R。我们的工作揭示了遗传对皮肤衰老的贡献，并证实了以前的发现，表明色素沉着是皮肤衰老的关键决定因素。
Loss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies of a measure of skin pattern (microtopography score) damage in 1,671 twin pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We identified that rs185146 near SLC45A2 is associated with a skin aging trait at genome-wide significance (P = 4.1 x 10(-9)); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (P = 8.8 x 10(-13)) and rs4268748 near MC1R (P = 1.2 x 10(-15)). At all three loci we highlight putative functionally relevant SNPs. There are a number of red hair/low pigmentation alleles of MC1R; we found that together these MC1R alleles explained 4.1% of variance in skin pattern damage. We also show that skin aging and reported experience of sunburns was proportional to the degree of penetrance for red hair of alleles of MC1R. Our work has uncovered genetic contributions to skin aging and confirmed previous findings, showing that pigmentation is a critical determinant of skin aging.