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.