Genome-wide association shows that pigmentation genes play a role in skin aging

Matthew H Law, Sarah E. Medland, Gu Zhu, Seyhan Yazar, Ana Viñuela, Leanne Wallace, Sri Niranjan Shekar, David L Duffy, Veronique Bataille, Dan Glass, Tim D Spector, Diane Wood, MuTHER Consortium, Scott D. Gordon, Julie M Barbour, Anjali K Henders, Alex W Hewitt, Grant W. Montgomery, Richard A Sturm, David A Mackey & 3 others Adèle C Green, Nicholas G Martin, Stuart MacGregor

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 × 10(-9)); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (P = 8.8 × 10(-13)) and rs4268748 near MC1R (P = 1.2 × 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.

Original languageEnglish
Pages (from-to)1887-1894
JournalJournal of Investigative Dermatology
Volume137
Issue number9
DOIs
Publication statusPublished - Sep 2017

Fingerprint

Skin Aging
Skin
Genes
Genome
Alleles
Pigmentation
Hair
Aging of materials
Sunburn
Penetrance
Genome-Wide Association Study
Skin Neoplasms
Keratinocytes
Single Nucleotide Polymorphism
Meta-Analysis

Cite this

Law, M. H., Medland, S. E., Zhu, G., Yazar, S., Viñuela, A., Wallace, L., ... MacGregor, S. (2017). Genome-wide association shows that pigmentation genes play a role in skin aging. Journal of Investigative Dermatology, 137(9), 1887-1894. https://doi.org/10.1016/j.jid.2017.04.026
Law, Matthew H ; Medland, Sarah E. ; Zhu, Gu ; Yazar, Seyhan ; Viñuela, Ana ; Wallace, Leanne ; Shekar, Sri Niranjan ; Duffy, David L ; Bataille, Veronique ; Glass, Dan ; Spector, Tim D ; Wood, Diane ; MuTHER Consortium ; Gordon, Scott D. ; Barbour, Julie M ; Henders, Anjali K ; Hewitt, Alex W ; Montgomery, Grant W. ; Sturm, Richard A ; Mackey, David A ; Green, Adèle C ; Martin, Nicholas G ; MacGregor, Stuart. / Genome-wide association shows that pigmentation genes play a role in skin aging. In: Journal of Investigative Dermatology. 2017 ; Vol. 137, No. 9. pp. 1887-1894.
@article{aab9aa393fe1415bb60778b7e91aaf1a,
title = "Genome-wide association shows that pigmentation genes play a role in skin aging",
abstract = "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 × 10(-9)); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (P = 8.8 × 10(-13)) and rs4268748 near MC1R (P = 1.2 × 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.",
keywords = "Journal Article",
author = "Law, {Matthew H} and Medland, {Sarah E.} and Gu Zhu and Seyhan Yazar and Ana Vi{\~n}uela and Leanne Wallace and Shekar, {Sri Niranjan} and Duffy, {David L} and Veronique Bataille and Dan Glass and Spector, {Tim D} and Diane Wood and {MuTHER Consortium} and Gordon, {Scott D.} and Barbour, {Julie M} and Henders, {Anjali K} and Hewitt, {Alex W} and Montgomery, {Grant W.} and Sturm, {Richard A} and Mackey, {David A} and Green, {Ad{\`e}le C} and Martin, {Nicholas G} and Stuart MacGregor",
note = "Copyright {\circledC} 2017 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = "9",
doi = "10.1016/j.jid.2017.04.026",
language = "English",
volume = "137",
pages = "1887--1894",
journal = "The Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Academic Press",
number = "9",

}

Law, MH, Medland, SE, Zhu, G, Yazar, S, Viñuela, A, Wallace, L, Shekar, SN, Duffy, DL, Bataille, V, Glass, D, Spector, TD, Wood, D, MuTHER Consortium, Gordon, SD, Barbour, JM, Henders, AK, Hewitt, AW, Montgomery, GW, Sturm, RA, Mackey, DA, Green, AC, Martin, NG & MacGregor, S 2017, 'Genome-wide association shows that pigmentation genes play a role in skin aging' Journal of Investigative Dermatology, vol. 137, no. 9, pp. 1887-1894. https://doi.org/10.1016/j.jid.2017.04.026

Genome-wide association shows that pigmentation genes play a role in skin aging. / Law, Matthew H; Medland, Sarah E.; Zhu, Gu; Yazar, Seyhan; Viñuela, Ana; Wallace, Leanne; Shekar, Sri Niranjan; Duffy, David L; Bataille, Veronique; Glass, Dan; Spector, Tim D; Wood, Diane; MuTHER Consortium; Gordon, Scott D.; Barbour, Julie M; Henders, Anjali K; Hewitt, Alex W; Montgomery, Grant W.; Sturm, Richard A; Mackey, David A; Green, Adèle C; Martin, Nicholas G; MacGregor, Stuart.

In: Journal of Investigative Dermatology, Vol. 137, No. 9, 09.2017, p. 1887-1894.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association shows that pigmentation genes play a role in skin aging

AU - Law, Matthew H

AU - Medland, Sarah E.

AU - Zhu, Gu

AU - Yazar, Seyhan

AU - Viñuela, Ana

AU - Wallace, Leanne

AU - Shekar, Sri Niranjan

AU - Duffy, David L

AU - Bataille, Veronique

AU - Glass, Dan

AU - Spector, Tim D

AU - Wood, Diane

AU - MuTHER Consortium

AU - Gordon, Scott D.

AU - Barbour, Julie M

AU - Henders, Anjali K

AU - Hewitt, Alex W

AU - Montgomery, Grant W.

AU - Sturm, Richard A

AU - Mackey, David A

AU - Green, Adèle C

AU - Martin, Nicholas G

AU - MacGregor, Stuart

N1 - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2017/9

Y1 - 2017/9

N2 - 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 × 10(-9)); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (P = 8.8 × 10(-13)) and rs4268748 near MC1R (P = 1.2 × 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.

AB - 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 × 10(-9)); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (P = 8.8 × 10(-13)) and rs4268748 near MC1R (P = 1.2 × 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.

KW - Journal Article

U2 - 10.1016/j.jid.2017.04.026

DO - 10.1016/j.jid.2017.04.026

M3 - Article

VL - 137

SP - 1887

EP - 1894

JO - The Journal of Investigative Dermatology

JF - The Journal of Investigative Dermatology

SN - 0022-202X

IS - 9

ER -