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

被引：1

作者：

Vollenbrock, Charlotte E. ^{[1
]}

Roshandel, Delnaz ^{[2
]}

van der Klauw, Melanie M. ^{[1
]}

Wolffenbuttel, Bruce H. R. ^{[1
]}

Paterson, Andrew D. ^{[2
,3
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands

[2] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON, Canada

[3] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Biostat & Epidemiol, Toronto, ON, Canada

来源：

BMC GENOMICS | 2022年 / 23卷 / 01期

关键词：

Skin Autofluorescence; Genome-wide association study; Screening; Single nucleotide polymorphism; Coffee; Skin Pigmentation; GLYCATION END-PRODUCTS; INTRINSIC FLUORESCENCE; COMPLICATIONS; GENE; DYSFUNCTION; STRESS; VALUES;

D O I：

10.1186/s12864-022-09062-x

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Background: 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). Results: In 27,534 participants without diabetes the heritability estimate of lnSAF was 33% & PLUSMN; 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 x 10(-8)): 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). Conclusions: 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.

引用

页数：18

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