Genome-wide association study identifies novel loci associated with skin autofluorescence in individuals without diabetes

• Published in: BMC genomics Vol. 23; no. 1; p. 840
• Main Authors: Vollenbrock, Charlotte E, Roshandel, Delnaz, van der Klauw, Melanie M, Wolffenbuttel, Bruce H R, Paterson, Andrew D
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19.12.2022; BioMed Central; BMC
• Subjects: Advanced glycation end products; Advanced glycosylation end products; Age; Analysis; Arylamine N-Acetyltransferase; Body mass index; Cardiovascular Diseases; Chromosomes; Coffee; Cohort analysis; Complications; CYP1A2 protein; Cytochrome P450; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Gene loci; Genetic diversity; Genetic variance; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Genotype & phenotype; Glycation End Products, Advanced - analysis; Glycosylation; Heritability; Humans; Laboratories; Light; Medical screening; Methods; Mortality; Physiological aspects; Questionnaires; Screening; Single nucleotide polymorphism; Skin; Skin - chemistry; Skin Autofluorescence; Skin Pigmentation; Netherlands; Screening; Single nucleotide polymorphism; Genome-wide association study; Skin Autofluorescence; Coffee; Skin Pigmentation
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-022-09062-x

Skin autofluorescence (SAF) is a non-invasive measure reflecting accumulation of advanced glycation endproducts (AGEs) in the skin. Higher SAF levels are associated with an increased risk of developing type 2 diabetes and cardiovascular disease. An earlier genome-wide association study (GWAS) revealed a strong association between NAT2 variants and SAF. The aim of this study was to calculate SAF heritability and to identify additional genetic variants associated with SAF through genome-wide association studies (GWAS). In 27,534 participants without diabetes the heritability estimate of lnSAF was 33% ± 2.0% (SE) in a model adjusted for covariates. In meta-GWAS for lnSAF five SNPs, on chromosomes 8, 11, 15 and 16 were associated with lnSAF (P < 5 × 10 ): 1. rs2846707 (Chr11:102,576,358,C > T), which results in a Met30Val missense variant in MMP27 exon 1 (NM_022122.3); 2. rs2470893 (Chr15:75,019,449,C > T), in intergenic region between CYP1A1 and CYP1A2; with attenuation of the SNP-effect when coffee consumption was included as a covariate; 3. rs12931267 (Chr16:89,818,732,C > G) in intron 30 of FANCA and near MC1R; and following conditional analysis 4. rs3764257 (Chr16:89,800,887,C > G) an intronic variant in ZNF276, 17.8 kb upstream from rs12931267; finally, 30 kb downstream from NAT2 5. rs576201050 (Chr8:18,288,053,G > A). This large meta-GWAS revealed five SNPs at four loci associated with SAF in the non-diabetes population. Further unravelling of the genetic architecture of SAF will help in improving its utility as a tool for screening and early detection of diseases and disease complications.