A genome wide association study identifies new genes potentially associated with eyelid sagging.

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10-10 ) and rs4746957 (P = 1.06 × 10-8 ), were significantly associated with eyelid sagging severity. The rs16927253-T and rs4746957-A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.

A genome-wide association study in Caucasian women points out a putative role of the STXBP5L gene in facial photoaging.

A genome-wide association study (GWAS) was conducted on 502 French middle-aged Caucasian women to identify genetic factors that may affect skin aging severity. A high-throughput Illumina Human Omni1-Quad beadchip was used. After single-nucleotide polymorphism (SNP) quality controls, 795,063 SNPs remained for analysis purposes. Possible stratification was first examined using the Eigenstrat method, and then the relationships between genotypes and four skin aging indicators (global photoaging, lentigines, wrinkles, and sagging) were investigated separately by linear regressions adjusted on age, smoking habits, lifetime sun exposure, hormonal status, and the two main Eigen vectors. One signal passed the Bonferroni threshold (P=1.53 × 10(-8)) and was significantly associated with global photoaging. It was also correlated with the wrinkling score and the sagging score. According to HapMap, this SNP, rs322458, was in linkage disequilibrium (LD) with intronic SNPs of the STXBP5L gene, which is expressed in the skin. In addition, it was also in LD with another SNP that increases the expression of the FBXO40 gene in the skin. These two genes, which were not previously described in the context of aging, may constitute good candidates for the investigation of molecular mechanisms of skin photoaging.