Journal: Journal of Physiological Anthropology
Article Title: A genome-wide association study identifies that SAMD5 interacts with regular Sun exposure to influence nasolabial folds development
doi: 10.1186/s40101-026-00423-z
Figure Lengend Snippet: Mutually concordant genetic and expression-based evidence linking the minor t allele of rs844607 with nasolabial folds through SAMD5 expression regulation. This figure summarises three complementary lines of evidence: genome-wide association study (GWAS), expression quantitative trait locus (eQTL), and differential gene expression (DEG), that together support the involvement of SAMD5 in nasolabial folds. First, the GWAS evidence (previously described in Fig. a) shows a GWAS association between the minor t allele of rs844607 and nasolabial folds among participants with regular Sun exposure ( n = 887), with the lead SNP reaching p = 2.27 × 10 −8 and an adjusted odds ratio (AOR) [95% confidence interval (CI)] = 2.67 [1.89–3.77]. The Manhattan and quantile–quantile (QQ) plots indicate a clear association peak at the SAMD5 locus and negligible genomic inflation (λ = 1.00353), suggesting a genuine signal rather than population stratification. Second, eQTL analyses from the Genotype-Tissue Expression (GTEx) portal and the eQTLGen consortium consistently show that the minor t allele of rs844607 decreases SAMD5 expression in an additive manner. In GTEx, the violin plot of normalised expression shows progressively reduced SAMD5 levels from CC to TC to TT genotypes (normalised effect size = − 0.72, p = 2.79 × 10 −52 ; CC = 316, TC = 292, TT = 73), supporting the effect of varying copies of the minor t allele on SAMD5 expression levels. Similarly, eQTLGen reports a significant negative association ( Z -score = 6.1605, false discovery rate (FDR) p -value = 6.59 × 10 −6 ). Third, differential expression analysis from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) dataset GSE200002 demonstrates that among Sun-exposed individuals, chronologically older adults exhibit significantly reduced SAMD5 expression (log fold change = − 0.639, adjusted p = 7.57 × 10 −3 ). Collectively, these data form a coherent model in which the minor t allele of rs844607 enhances the binding affinity of hsa-miR-216a and hsa-miR-485-5p to SAMD5 , resulting in reduced SAMD5 transcription and diminished melanogenic potential. This reduction may weaken melanin-based UV protection, thereby accelerating photo-ageing processes such as nasolabial fold development. The mutually supported GWAS, eQTL, and DEG findings strengthens the conclusion that SAMD5 genetic variants modulate gene expression to influence the skin’s photo-protective capacity and facial wrinkle formation in Sun-exposed individuals. Abbreviations: λ, Genomic inflation factor; AOR, adjusted odds ratio; CI, confidence interval; DEG, differentially expressed gene; eQTL, expression quantitative trait locus; FDR, false discovery rate; GEO, gene expression omnibus; GTEx, genotype-tissue expression portal; GWAS, genome-wide association study; NCBI, National Center for Biotechnology Information; SAMD5 , sterile alpha motif domain containing 5
Article Snippet: Third, differential expression analysis from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) dataset GSE200002 demonstrates that among Sun-exposed individuals, chronologically older adults exhibit significantly reduced SAMD5 expression (log fold change = − 0.639, adjusted p = 7.57 × 10 −3 ).
Techniques: Expressing, GWAS, Gene Expression, Quantitative Proteomics, Binding Assay, Sterility
![Mutually concordant genetic and expression-based evidence linking the minor t allele of rs844607 with nasolabial folds through SAMD5 expression regulation. This figure summarises three complementary lines of evidence: genome-wide association study (GWAS), expression quantitative trait locus (eQTL), and differential gene expression (DEG), that together support the involvement of SAMD5 in nasolabial folds. First, the GWAS evidence (previously described in Fig. a) shows a GWAS association between the minor t allele of rs844607 and nasolabial folds among participants with regular Sun exposure ( n = 887), with the lead SNP reaching p = 2.27 × 10 −8 and an adjusted odds ratio (AOR) [95% confidence interval (CI)] = 2.67 [1.89–3.77]. The Manhattan and quantile–quantile (QQ) plots indicate a clear association peak at the SAMD5 locus and negligible genomic inflation (λ = 1.00353), suggesting a genuine signal rather than population stratification. Second, eQTL analyses from the Genotype-Tissue Expression (GTEx) portal and the eQTLGen consortium consistently show that the minor t allele of rs844607 decreases SAMD5 expression in an additive manner. In GTEx, the violin plot of normalised expression shows progressively reduced SAMD5 levels from CC to TC to TT genotypes (normalised effect size = − 0.72, p = 2.79 × 10 −52 ; CC = 316, TC = 292, TT = 73), supporting the effect of varying copies of the minor t allele on SAMD5 expression levels. Similarly, eQTLGen reports a significant negative association ( Z -score = 6.1605, false discovery rate (FDR) p -value = 6.59 × 10 −6 ). Third, differential expression analysis from the National Center for Biotechnology Information <t>(NCBI)</t> Gene Expression Omnibus (GEO) dataset <t>GSE200002</t> demonstrates that among Sun-exposed individuals, chronologically older adults exhibit significantly reduced SAMD5 expression (log fold change = − 0.639, adjusted p = 7.57 × 10 −3 ). Collectively, these data form a coherent model in which the minor t allele of rs844607 enhances the binding affinity of hsa-miR-216a and hsa-miR-485-5p to SAMD5 , resulting in reduced SAMD5 transcription and diminished melanogenic potential. This reduction may weaken melanin-based UV protection, thereby accelerating photo-ageing processes such as nasolabial fold development. The mutually supported GWAS, eQTL, and DEG findings strengthens the conclusion that SAMD5 genetic variants modulate gene expression to influence the skin’s photo-protective capacity and facial wrinkle formation in Sun-exposed individuals. Abbreviations: λ, Genomic inflation factor; AOR, adjusted odds ratio; CI, confidence interval; DEG, differentially expressed gene; eQTL, expression quantitative trait locus; FDR, false discovery rate; GEO, gene expression omnibus; GTEx, genotype-tissue expression portal; GWAS, genome-wide association study; NCBI, National Center for Biotechnology Information; SAMD5 , sterile alpha motif domain containing 5](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_9621/pmc13059621/pmc13059621__40101_2026_423_Fig3_HTML.jpg)