Genome-wide Association Studies of Retinal Vessel Tortuosity Identify Numerous Novel Loci Revealing Genes and Pathways Associated With Ocular and Cardiometabolic Diseases
Mattia Tomasoni, Michael J. Beyeler, Sofía Ortín Vela, Ninon Mounier, Eleonora Porcu, Tanguy Corre, Daniel Krefl, Alexander L. Button, Hana Abouzeid, Lazaros Konstantinidis, Murielle Bochud, Reinier O. Schlingemann, Ciara Bergin, Sven Bergmann
Abstract
Purpose: To identify novel susceptibility loci for retinal vascular tortuosity, to better understand the molecular mechanisms modulating this trait, and reveal causal relationships with diseases and their risk factors. Design: Genome-wide Association Studies (GWAS) of vascular tortuosity of retinal arteries and veins followed by replication meta-analysis and Mendelian randomization (MR). Participants: (n = 512). Methods: . Main Outcome Measure: We evaluated the genetic association of retinal tortuosity, measured by the distance factor. Results: . These tortuosity genes were overexpressed in arteries and heart muscle and linked to pathways related to the structural properties of the vasculature. We demonstrated that retinal tortuosity loci served pleiotropic functions as cardiometabolic disease variants and risk factors. Concordantly, MR revealed causal effects between tortuosity, body mass index, and low-density lipoprotein. Conclusions: Several alleles associated with retinal vessel tortuosity suggest a common genetic architecture of this trait with ocular diseases (glaucoma, myopia), cardiovascular diseases, and metabolic syndrome. Our results shed new light on the genetics of vascular diseases and their pathomechanisms and highlight how GWASs and heritability can be used to improve phenotype extraction from high-dimensional data, such as images. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.