Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment.

The genetic basis of earlobe attachment has been a matter of debate since the early 20th century, such that geneticists argue both for and against polygenic inheritance. Recent genetic studies have identified a few loci associated with the trait, but large-scale analyses are still lacking. Here, we performed a genome-wide association study of lobe attachment in a multiethnic sample of 74,660 individuals from four cohorts (three with the trait scored by an expert rater and one with the trait self-reported). Meta-analysis of the three expert-rater-scored cohorts revealed six associated loci harboring numerous candidate genes, including EDAR, SP5, MRPS22, ADGRG6 (GPR126), KIAA1217, and PAX9. The large self-reported 23andMe cohort recapitulated each of these six loci. Moreover, meta-analysis across all four cohorts revealed a total of 49 significant (p < 5 × 10-8) loci. Annotation and enrichment analyses of these 49 loci showed strong evidence of genes involved in ear development and syndromes with auricular phenotypes. RNA sequencing data from both human fetal ear and mouse second branchial arch tissue confirmed that genes located among associated loci showed evidence of expression. These results provide strong evidence for the polygenic nature of earlobe attachment and offer insights into the biological basis of normal and abnormal ear development.

Genome-wide scan identified genetic variants associated with skin aging in a Chinese female population.

BACKGROUND: The progression of human skin aging has a strong genetic basis. However, recent studies have mainly focused on Caucasian populations and we have thus performed a genetic association study on skin aging signs in Han Chinese population. OBJECTIVE: To investigate genetic risk factors in skin aging in Han Chinese female, we performed a genome-wide association study. METHODS: We collected genotype data from 1534 Han Chinese female from Taizhou cohort and evaluated 15 skin aging phenotypes by using the validated skin aging SCINEXA™ score. Genetic associations were tested by linear and logistic regression analyses and adjusted for potential confounders. RESULTS: Six genomic regions significantly associated with a risk for skin aging were revealed : 6q24.2 (rs3804540, P=4.6×10-9, additive model) with size of pigmented spots on forehead, 10q26.13 (rs4962295, P=1.9 ×10-8, additive model) with wrinkles under eyes, 15q21.1 (rs28392847, P=1.6×10-8, additive model) with crow's feet, 2p25.1 (rs191497052, P=5.5×10-9, dominant model) with telangiectasia, 13q34 (rs3825460, P=3.7×10-8, dominant model) with size of pigmented spots on cheeks and 16p13.11(rs76053540, P=5.0×10-9, dominant model) with nasolabialfold. The signal on 15q21.1 was replicated in the meta-analysis with two independent Caucasian cohorts (P=8.6×10-10). We have also successfully replicated in our cohort an association between SNP rs1048943 of gene CYP1A1 (P=7.1 × 10-4) and pigmented spots on cheeks previously described in Caucasian cohort. CONCLUSIONS: Our study has identified new genetic risk factors for signs of skin aging in the Han Chinese. This study suggests there are differences in genetic susceptibility to skin aging between Caucasians and the Han Chinese.

Genetic variants associated with skin aging in the Chinese Han population.

BACKGROUND: The progression and manifestation of human skin aging has a strong genetic basis; however, most of the supporting evidence has been gathered in Caucasian populations. The genetic contribution to the variation in skin aging in non-Caucasian populations is poorly understood. OBJECTIVE: To investigate the genetic risk factors of relevance for skin aging in East Asians, we conducted the first candidate gene study for signs of skin aging in Han Chinese. METHODS: We collected skin aging and genotype data in 502 female Han Chinese from the Taizhou cohort. We evaluated skin aging by the validated skin aging score SCINEXA™. Confounding factors were assessed through a questionnaire. We obtained the genotype data for 21 candidate SNPs and for a further 509 SNPs from 16 related candidate genes. Associations were tested by linear and logistic regression analyses and adjusted for potential confounders. RESULTS: Our candidate study found a significant association between SNP rs2066853 in exon 10 of the aryl hydrocarbon receptor gene AHR and crow's feet. In addition, we found a significant association between SNP rs10733310 in intron 5 of BNC2 and pigment spots on the arms, and between SNP rs11979919, 3kb downstream of COL1A2, and laxity of eyelids. CONCLUSIONS: Our results identified genetic risk factors for signs of skin aging (pigmentation, wrinkles or laxity) in Han Chinese. We also found that the manifestation of skin aging is further modified by anatomical site. Together with previous work, our results also suggest that different genetic variants could be responsible for distinct skin aging signs characteristic of Caucasians compared to East Asians.

Indoor PM2.5 exposure affects skin aging manifestation in a Chinese population.

Traffic-related air pollution is known to be associated with skin aging manifestations. We previously found that the use of fossil fuels was associated with skin aging, but no direct link between indoor air pollutants and skin aging manifestations has ever been shown. Here we directly measured the indoor PM2.5 exposure in 30 households in Taizhou, China. Based on the directly measured PM2.5 exposure and questionnaire data of indoor pollution sources, we built a regression model to predict the PM2.5 exposure in larger datasets including an initial examination group (N = 874) and a second examination group (N = 1003). We then estimated the association between the PM2.5 exposure and skin aging manifestations by linear regression. In the initial examination group, we showed that the indoor PM2.5 exposure levels were positively associated with skin aging manifestation, including score of pigment spots on forehead (12.5% more spots per increase of IQR, P-value 0.0371), and wrinkle on upper lip (7.7% more wrinkle on upper lip per increase of IQR, P-value 0.0218). The results were replicated in the second examination group as well as in the pooled dataset. Our study provided evidence that the indoor PM2.5 exposure is associated with skin aging manifestation in a Chinese population.

Epidemiological evidence that indoor air pollution from cooking with solid fuels accelerates skin aging in Chinese women.

BACKGROUND: Recently, we showed that outdoor air pollution exposure from traffic and industry is associated with an increased risk of skin aging in Caucasian women. In China, indoor air pollution exposure caused by the use of solid fuels like coal is a major health problem and might also increase the risk of skin aging in Chinese women. OBJECTIVE: As cooking with solid fuels is a major source of indoor air pollution exposure in China, we aimed to test if cooking with solid fuels is associated with more pronounced skin aging in Chinese women. METHODS: We conducted two cross-sectional studies in China to assess the association between cooking with solid fuels and signs of skin aging. In Pingding (in northern China) we assessed N=405 and in Taizhou (in southern China) N=857 women between 30 and 90 years of age. Skin aging was evaluated by the SCINEXA score. Indoor air pollution exposure, sun exposure, smoking and other confounders were assessed by questionnaires. Associations were then tested by linear and logistic regression analyses adjusted for further confounders. RESULTS: The analysis showed that cooking with solid fuels was significantly associated with a 5-8% more severe wrinkle appearance on face and an 74% increased risk of having fine wrinkles on back of hands in both studies combined, independent of age and other influences on skin aging. CONCLUSION: The present studies thus corroborate our previous finding that air pollution is associated with skin aging and extend it by showing that indoor air pollution might be another risk factor for skin aging.