WHAT CAN GENETICS TELL US ABOUT OUR SKIN?

It’s clear that both nature and nurture play a role in skin appearance as we age. Regarding nurture (extrinsic factors), lifestyle choices around diet, fitness, sun exposure, and substance use reflect heavily on skin quality [1]. And regarding nature (intrinsic factors), our racial background(s) determine skin and hair tone, thickness, and textures [2–4]. However, outside of melanin production, what other genetic differences contribute to skin aging and resilience to stressors? Furthermore, could a deeper understanding of our genetics lead us to personalized skin care solutions?

SINGLE NUCLEOTIDE POLYMORPHISM (SNP)

Phenotypic, or observable variability between individuals like eye color, hair color, skin tone, and even disease risk is largely explained by SNPs [5,6]. SNP is a genetics term that refers to a single change at a specific location in the DNA sequence that correlates with some sort of identifiable trait in at least 1% of the population [7]. While some traits are visible to the naked eye, recent research has revealed that SNPs also influence our ability to produce collagen, maintain moisture content, accumulate wrinkles, and our sensitivity to certain extrinsic stressors [3,8–11]. So, how are SNPs discovered and how do we find out which ones are relevant to us?

GENOME WIDE ASSOCIATION STUDIES (GWAS)

GWAS are large, cross-sectional studies that examine the sequenced genomes of thousands to millions of participants. For example, in a study of over 26,000 individuals, researchers examined the genomes of over 3,000 acne vulgaris sufferers versus non-affected individuals. They were able to identify 15 SNPs that were statistically unique to the population of acne vulgaris sufferers [12]. Other inquiries have identified SNPs that correlate with skin aging in both European and more melanin-rich Latin American populations [13]. GWAS studies by large teams of skilled researchers are helping us understand how much of the skin aging process we have control over and choose the most effective therapies [14].

PERSONALIZED SKIN CARE 

Because there are tens to hundreds of SNPs that can correlate with a specific skin phenotype, it will take a while for commercial skin care products to account for our specific genetic predispositions. In the example of acne described above, each SNP represents a possible enzyme or affected pathway that could be targeted to treat acne and further clinical research must be done to develop effective products. For those with an interest in biohacking, having your entire genome sequenced through companies like Nebula Genomics can allow you the freedom to compare your genome with the results of this preliminary literature. You may gain a better understanding of your risks of hyperpigmentation, photoaging, acne, and skin cancer. Interestingly, some SNPs associated with reduced photoaging can be traced back to specific racial backgrounds while others are relevant across different ethnicities [4,13,14]. There is much more to the genetic determinants of skin aging than melanin content and we have barely scratched the surface of this exciting skin care revolution.

Sources:

[1] Vierkötter A, Krutmann J (2012) Environmental influences on skin aging and ethnic-specific manifestations. Dermatoendocrinol 4, 227–231.

[2] Rawlings AV (2006) Ethnic skin types: are there differences in skin structure and function?1. International Journal of Cosmetic Science 28, 79–93.

[3] Del Bino S, Duval C, Bernerd F (2018) Clinical and Biological Characterization of Skin Pigmentation Diversity and Its Consequences on UV Impact. Int J Mol Sci 19, 2668.

[4] Walker JM, Garcet S, Aleman JO, Mason CE, Danko D, Butler D, Zuffa S, Swann JR, Krueger J, Breslow JL, Holt PR (2020) Obesity and ethnicity alter gene expression in skin. Sci Rep 10, 14079.

[5] Antoniou AC, Spurdle AB, Sinilnikova OM, Healey S, Pooley KA, Schmutzler RK, Versmold B, Engel C, Meindl A, Arnold N, Hofmann W, Sutter C, Niederacher D, Deissler H, Caldes T, Kämpjärvi K, Nevanlinna H, Simard J, Beesley J, Chen X, Kathleen Cuningham Consortium for Research into Familial Breast Cancer, Neuhausen SL, Rebbeck TR, Wagner T, Lynch HT, Isaacs C, Weitzel J, Ganz PA, Daly MB, Tomlinson G, Olopade OI, Blum JL, Couch FJ, Peterlongo P, Manoukian S, Barile M, Radice P, Szabo CI, Pereira LHM, Greene MH, Rennert G, Lejbkowicz F, Barnett-Griness O, Andrulis IL, Ozcelik H, OCGN, Gerdes A-M, Caligo MA, Laitman Y, Kaufman B, Milgrom R, Friedman E, Swedish BRCA1 and BRCA2 study collaborators, Domchek SM, Nathanson KL, Osorio A, Llort G, Milne RL, Benítez J, Hamann U, Hogervorst FBL, Manders P, Ligtenberg MJL, van den Ouweland AMW, DNA-HEBON collaborators, Peock S, Cook M, Platte R, Evans DG, Eeles R, Pichert G, Chu C, Eccles D, Davidson R, Douglas F, EMBRACE, Godwin AK, Barjhoux L, Mazoyer S, Sobol H, Bourdon V, Eisinger F, Chompret A, Capoulade C, Bressac-de Paillerets B, Lenoir GM, Gauthier-Villars M, Houdayer C, Stoppa-Lyonnet D, GEMO, Chenevix-Trench G, Easton DF, CIMBA (2008) Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet 82, 937–948.

[6] Reis LB, Bakos RM, Vianna FSL, Macedo GS, Jacovas VC, Ribeiro-dos-Santos AM, Santos S, Bakos L, Ashton-Prolla P (2020) Skin pigmentation polymorphisms associated with increased risk of melanoma in a case-control sample from southern Brazil. BMC Cancer 20, 1069.

[7] Shastry BS (2009) SNPs: impact on gene function and phenotype. Methods Mol Biol 578, 3–22.

[8] Park S, Kang S, Lee WJ (2021) Menopause, Ultraviolet Exposure, and Low Water Intake Potentially Interact with the Genetic Variants Related to Collagen Metabolism Involved in Skin Wrinkle Risk in Middle-Aged Women. Int J Environ Res Public Health 18, 2044.

[9] Markiewicz E, Idowu OC (2018) Personalized skincare: from molecular basis to clinical and commercial applications. Clin Cosmet Investig Dermatol 11, 161–171.

[10] Chan T-F, Poon A, Basu A, Addleman NR, Chen J, Phong A, Byers PH, Klein TE, Kwok P-Y (2008) Natural variation in four human collagen genes across an ethnically diverse population. Genomics 91, 307–314.

[11] Zhang M, Li B, Wu S, Tan J, Yang Y, Marini A, Vierkötter A, Zhang J, Li H, Schikowski T, Jin L, Krutmann J, Wang S (2017) A Genome-Wide Association Study of Basal Transepidermal Water Loss Finds that Variants at 9q34.3 Are Associated with Skin Barrier Function. J Invest Dermatol 137, 979–982.

[12] Petridis C, Navarini AA, Dand N, Saklatvala J, Baudry D, Duckworth M, Allen MH, Curtis CJ, Lee SH, Burden AD, Layton A, Bataille V, Pink AE, Carlavan I, Voegel JJ, Spector TD, Trembath RC, McGrath JA, Smith CH, Barker JN, Simpson MA (2018) Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne. Nat Commun 9, 5075.

[13] Langton AK, Watson REB (2021) Identification of novel skin ageing genes: evidence from across the pigmentary continuum. British Journal of Dermatology 185, 883–884.

[14] Naval J, Alonso V, Herranz MA (2014) Genetic polymorphisms and skin aging: the identification of population genotypic groups holds potential for personalized treatments. Clin Cosmet Investig Dermatol 7, 207–214.