JOURNAL OF COSMETIC SCIENCE 74 because universality can be achieved by applying tertile-divided scoring to the measured values, even when using different equipment or measuring different areas. There were also some limitations to our research. First, reproducibility was not verifi ed in our study because no replication study exists. However, our fi ndings provide scientifi c evi- dence, given the large sample size, that are considered to be reliable enough to include the OCA2 SNP (rs74653330) (31,32), which is known to be associated with pigmentation. As the results of these phenotypic studies show, there is a link between genetic variation and changes in skin characteristics which allows us to produce skin prediction models. If we can identify gene variants that affect skin phenotype changes, we can provide a per- sonalized guide to apply to lifestyle, diet, and makeup and help prevent and resolve skin problems using customized cosmetics. By providing relief and therapeutic intervention in the early stages of symptoms, cosmetic problems and medical costs can be reduced. These results can help us understand the personality of each individual’s skin and provide personalized cosmetics and skincare. In addition, we can also provide customized services based on genotype. We suggest that this study is a valuable foundation to produce cus- tomized cosmetics, wherein ingredients and materials may be added to the cosmetics for the prevention of skin damage or application of functional cosmetics, according to skin characteristic markers through genetic testing. WRINKLES Among the various skin traits examined, wrinkles were the primary skin phenotype show- ing the most obvious change. Generally, wrinkles appear naturally because of aging, which is an interesting fi eld in cosmetic dermatology because it is a phenotype that does not re- cover completely, unlike scars or disease (33). However, wrinkles are not only caused by natural aging but can also be caused or accelerated by external factors and internal abnor- malities (34). In particular, the internal immune response, triggered by environmental fac- tors, can produce chronic infl ammation and accelerate the occurrence of wrinkles (34). Aging results in the accumulation of the B-cell receptor, which increases the risk of chronic infl ammation stimulated through this receptor and its induced transcript, FCRL5 (35). FCRL3, a well-known member of the immunoglobulin receptor superfamily and one of several Fc receptor–like glycoproteins, has immunoreceptor tyrosine-based activation and inhibitory motifs in its cytoplasmic domain, which may play a role in the regulation of the immune system. According to our results, rs117381658 exists downstream of FCRL5 and can affect FCRL5 expression by forming a signifi cant SNP cluster related to chronic infl am- matory status (36). FCRL5 expression levels can affect the infl ammatory response and NF-κB, which can disrupt modulators of tissue homeostasis and affect skin aging (37). In addition, our study also identifi ed SNPs associated with wrinkles, such as rs1961184 (REEP3), rs1929013 (ADSS2), and rs7042102 (SPTLC1). The SNP rs1961184 is located downstream of REEP3 and has been reported to infl uence REEP3 expression patterns in the heart tissue. REEP3 is involved in GPCR signaling, affects the normal progression of mito- sis, and is reported to be related to aging (38). Although there are no reports of REEP3 di- rectly impacting skin aging, it is a potential marker of skin aging. The SNP rs1929013 is located downstream of ADSS2, which encodes an enzyme that converts inosine monophos- phate to adenosine monophosphate. Adenosine is a well-known factor involved in wrinkle improvement (39), and ADSS2 can regulate the function of adenosine (40). It is conceivable

GWAS OF SKIN AGING IN KOREAN POPULATION 75 therefore that ADSS2 may have an effect on wrinkles. In addition, rs7042102, which is another SNP identifi ed in this study, is a variant located downstream of the SPTLC1, for which its differences in expression, based on genotype in skin tissues, were confi rmed in the eQTL database. Previous reports suggest that SPTLC1 may be a causal gene that affects psoriatic lesions (41) and may also affect skin phenotype by functioning as a regulator of skin fi broblasts (42). SPTLC1 is involved in the synthesis of sphingolipids, which are sub- stances involved in maintaining the skin’s barrier and moisture (43) and exerts skin im- provement effects through skin moisturization and maintenance (44,45). From this perspective, SPTLC1 may affect skin aging and the generation of wrinkles, if it causes ab- normalities in skin maintenance. MOISTURE CONTENT The moisture content of the skin is closely related to the contraction of the stratum cor- neum. This outermost layer of the epidermis is important for the skin’s barrier function because it has various proteolytic effects related to skin changes as well as to exfoliation, lipid synthesis, and infl ammatory reactions (46). Dry skin and frequent infl ammatory reactions in the stratum corneum may lead to diseases, such as atopic dermatitis and pso- riasis. Internal factors involved in modulating the important characteristic of the skin moisture content include lipids of the stratum corneum, natural moisturizing factors, and external factors (47). However, there are still individual differences regarding changes in skin hydration, for which genetic variants have been highlighted as a likely explanatory factor and are currently being studied (15,48). Our results identifi ed six SNPs, rs9873353, rs34567709, rs1362404, rs7853290, rs143938096, and rs12955989, which were associ- ated with the skin moisture content. The SNP identifi ed as the most signifi cant marker of skin moisture in our results was rs9873353. This locus has several pseudogenes in the surrounding area, but no functional genes have been identifi ed. However, there are SNPs that are considered to have other potential functions. Potential functional effects are sug- gested for rs7853290 and rs143938096, which are associated with the CEMIP2 (TMEM2) and CTSH genes, respectively. Both of these genes can affect skin changes, especially CEMIP2, which regulates hyaluronan, a key component of physical functions of the skin, such as moisturization and lubrication (49). Regarding the differences in expression ac- cording to the SNPs in the eQTL database, although only adipose tissue eQTLs are in- cluded among the single-tissue eQTLs, the available multiple-tissue eQTLs confi rmed that altered expression of CEMIP2, based on the rs7853290 genotype, also appears in the skin tissue. Therefore, it is possible that this SNP is capable of providing moisture and functionally controlling the barrier, which may explain our results. PIGMENTATION Changes in pigmentation are largely visible and can be found in the hair and eyes, in addi- tion to local phenotypic variations in the skin. Pigmentation is the most studied topic among the various phenotypic variations of the skin and is caused by differences in melanin, where differences between individuals are caused by changes in the type, amount, or other parameters of melanin (13). These individual melanin differences are due to genetic