Novel Genetic Locus Influencing Retinal Venular Tortuosity Is Also Associated With Risk of Coronary Artery Disease
Year: 2019
Type: article
Study design: Observational Study
Abstract: Objective: The retina may provide readily accessible imaging biomarkers of global cardiovascular health. Increasing evidence suggests variation in retinal vascular traits is highly heritable. This study aimed to identify the genetic determinants of retinal vascular traits. Approach and Results: We conducted a meta-analysis of genome-wide association studies for quantitative retinal vascular traits derived using semi-automatic image analysis of digital retinal photographs from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside; N=1736) and ORCADES (Orkney Complex Disease Study; N=1358) cohorts. We identified a novel genome-wide significant locus at 19q13 ( ACTN4/CAPN12 ) for retinal venular tortuosity ( TortV ), and one at 13q34 ( COL4A2 ) for retinal arteriolar tortuosity ( TortA ); these 2 loci were subsequently confirmed in 3 independent cohorts (N total =1413). In the combined analysis of discovery and replication cohorts, the lead single-nucleotide polymorphism in ACTN4 / CAPN12 was rs1808382 (β s.d. =-0.109; SE=0.015; P =2.39×10- 13 ) and in COL4A2 was rs7991229 (β s.d. =0.103; SE=0.015; P =4.66×10- 12 ). Notably, the ACTN4 / CAPN12 locus associated with TortV is also associated with coronary artery disease, heart rate, and atrial fibrillation. Conclusions: Genetic determinants of retinal vascular tortuosity are also linked to cardiovascular health. These findings provide a molecular pathophysiological foundation for the use of retinal vascular traits as biomarkers for cardiovascular diseases.
Authors: Abirami Veluchamy, Lucia Ballerini, Veronique Vitart, Katharina E. Schraut, Mirna Kirin, Harry Campbell, Peter K. Joshi, Devanjali Relan, Sarah Harris, Ellie Brown, Suraj S. Vaidya, Baljean Dhillon, Kaixin Zhou, Ewan R. Pearson, Caroline Hayward, Ozren Polasek, Ian J. Deary, Thomas MacGillivray, James F. Wilson, Emanuele Trucco, Colin N.A. Palmer, Alexander S.F. Doney
Institutions: University of Dundee, Ninewells Hospital, Edinburgh Royal Infirmary, Western General Hospital, Institute of Genetics and Cancer, MRC Human Genetics Unit, University of Edinburgh, The Queen's Medical Research Institute, University of Split, BML Munjal University, Renji Hospital, University of Chinese Academy of Sciences
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Funders: Bill and Melinda Gates Foundation, Sanofi, Wellcome Trust, Scottish Government, Cancer Research UK, National Institute for Health and Care Research, Leverhulme Trust, Royal Society, Age UK, European Commission, University of Edinburgh, Hrvatska Zaklada za Znanost, Centre for Cognitive Ageing and Cognitive Epidemiology, Directorate for Biological Sciences, Medical Research Council, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Helmholtz Zentrum München, FP7 People: Marie-Curie Actions
Awards: WTCCC2 core activities., G1184531726, Centre for Cognitive Ageing & Cognitive Epidemiology, G1689944598, BBMRI - Large Prospective Cohorts, WTCCC2 core activities, Population pharmacogenetics of statin response., G2352317866, G3001543491, The UK Type 2 diabetes genetics consortium case-control collection: a resource for the genetic epidemiology of Type 2 diabetes., G3738692396, G3933842093, G4404013984, G4571683210, G4641403149, G4694539458, G4755160787, G4801199537, G4942547004, G5067462658, G5177881357, G5649515030, "Retinal Vascular Modeling, Measurement and Diagnosis", G666546157, Population pharmacogenetics of statin response., A genome-wide association study of non-pathological cognitive ageing, WTCCC2 core activities., G718988473, G7771854671, G7823839363, Multi-modal retinal biomarkers for vascular dementia: developing enabling image analysis tools, G8330560607, G970400076
OpenAlex ID: W2979401036