Genetics of facial telangiectasia in the Rotterdam Study: a genome‐wide association study and candidate gene approach

• Published in: Journal of the European Academy of Dermatology and Venereology Vol. 35; no. 3; pp. 749 - 754
• Main Authors: Mekić, S., Wigmann, C., Gunn, D.A., Jacobs, L.C., Kayser, M., Schikowski, T., Nijsten, T., Pardo, L.M.
• Format: Journal Article
• Language: English
• Published: England 01-03-2021
• Subjects: Aged; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Telangiectasis - genetics
• ISSN: 0926-9959; 1468-3083
• DOI: 10.1111/jdv.17014

Background
The severity of facial telangiectasia or red veins is associated with many lifestyle factors. However, the genetic predisposition remains unclear.
Objectives
We performed a genome‐wide association study (GWAS) on facial telangiectasia in the Rotterdam Study (RS) and tested for replication in two independent cohorts. Additionally, a candidate gene approach with known pigmentation genes was performed.
Methods
Facial telangiectasia were extracted from standardized facial photographs (collected from 2010–2013) of 2842 northwestern European participants (median age 66.9, 56.8% female) from the RS. Our GWAS top hits (P‐value <10−6) were tested for replication in 460 elderly women of the SALIA cohort and in 576 additional men and women of the RS. Associations of top single nucleotide polymorphisms (SNPs) with expression quantitative trait loci (eQTL) in various tissues were reviewed (GTEx database) alongside phenotype associations in the UK biobank database. SNP‐based associations between known pigmentation genes and facial telangiectasia were tested. Conditional analysis on skin colour was additionally performed.
Results
Our most significant GWAS signal was rs4417318 (P‐value 5.38*10−7), an intergenic SNP on chromosome 12 mapping to the SLC16A7 gene. Other suggestive SNPs tagged genes ZNF211, ZSCAN4, ICOS and KCNN3; SNP eQTLs and phenotype associations tagged links to the vascular system. However, the top signals did not pass significance in the two replication cohorts. The pigmentation genes KIAA0930, SLCA45A2 and MC1R, were significantly associated with telangiectasia in a candidate gene approach but not independently of skin colour.
Conclusion
In this GWAS on telangiectasia in a northwestern European population, no genome‐wide significant SNPs were found, although suggestive signals indicate genes involved in the vascular system might be involved in telangiectasia. Significantly associated pigmentation genes underline the link between skin colour and telangiectasia.