A novel genetic locus influencing retinal venular tortuosity is also associated with risk of coronary artery disease

Abirami Veluchamy; Lucia Ballerini; Veronique Vitart; Katharina E Schraut; Mirna Kirin; Harry Campbell; Peter Joshi; Devanjali Relan; Sarah Harris; Ellie Brown; Suraj S Vaidya; Baljean Dhillon; Kaixin Zhou; Ewan R Pearson; Caroline Hayward; Ozren Polasek; Ian Deary; Tom MacGillivray; James Wilson; Emmanuele Trucco; Colin N. A. Palmer; Alexander S. F. Doney

doi:10.1161/ATVBAHA.119.312552

A novel genetic locus influencing retinal venular tortuosity is also associated with risk of coronary artery disease

Abirami Veluchamy, Lucia Ballerini, Veronique Vitart, Katharina E Schraut, Mirna Kirin, Harry Campbell, Peter Joshi, Devanjali Relan, Sarah Harris, Ellie Brown, Suraj S Vaidya, Baljean Dhillon, Kaixin Zhou, Ewan R Pearson, Caroline Hayward, Ozren Polasek, Ian Deary, Tom MacGillivray, James Wilson, Emmanuele TruccoColin N. A. Palmer, Alexander S. F. Doney

Research output: Contribution to journal › Article › peer-review

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 (Ntotal=1413). In the combined analysis of discovery and replication cohorts, the lead single-nucleotide polymorphism in ACTN4/CAPN12 was rs1808382 (βs.d.=-0.109; SE=0.015; P=2.39×10-13) and in COL4A2 was rs7991229 (βs.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.

Original language	English
Pages (from-to)	2542-2552
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	39
Issue number	12
Early online date	10 Oct 2019
DOIs	https://doi.org/10.1161/ATVBAHA.119.312552
Publication status	Published - Dec 2019

Keywords / Materials (for Non-textual outputs)

atrial fibrillation
biomarkers
cardiovascular diseases
genome-wide association study
heart rate

Access to Document

10.1161/ATVBAHA.119.312552Licence: Creative Commons: Attribution (CC-BY)

VeluchamyATAVB2019NovelGeneticLocusInfluencingFinal published version, 642 KB

Cite this

Veluchamy, A., Ballerini, L., Vitart, V., Schraut, K. E., Kirin, M., Campbell, H., Joshi, P., Relan, D., Harris, S., Brown, E., Vaidya, S. S., Dhillon, B., Zhou, K., Pearson, E. R., Hayward, C., Polasek, O., Deary, I., MacGillivray, T., Wilson, J., ... Doney, A. S. F. (2019). A novel genetic locus influencing retinal venular tortuosity is also associated with risk of coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 39(12), 2542-2552. https://doi.org/10.1161/ATVBAHA.119.312552

@article{2d89a20319e34bc792994d5aea276e49,

title = "A novel genetic locus influencing retinal venular tortuosity is also associated with risk of coronary artery disease",

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 (Ntotal=1413). In the combined analysis of discovery and replication cohorts, the lead single-nucleotide polymorphism in ACTN4/CAPN12 was rs1808382 (βs.d.=-0.109; SE=0.015; P=2.39×10-13) and in COL4A2 was rs7991229 (βs.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.",

keywords = "atrial fibrillation, biomarkers, cardiovascular diseases, genome-wide association study, heart rate",

author = "Abirami Veluchamy and Lucia Ballerini and Veronique Vitart and Schraut, \{Katharina E\} and Mirna Kirin and Harry Campbell and Peter Joshi and Devanjali Relan and Sarah Harris and Ellie Brown and Vaidya, \{Suraj S\} and Baljean Dhillon and Kaixin Zhou and Pearson, \{Ewan R\} and Caroline Hayward and Ozren Polasek and Ian Deary and Tom MacGillivray and James Wilson and Emmanuele Trucco and Palmer, \{Colin N. A.\} and Doney, \{Alexander S. F.\}",

year = "2019",

month = dec,

doi = "10.1161/ATVBAHA.119.312552",

language = "English",

volume = "39",

pages = "2542--2552",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams and Wilkins",

number = "12",

}

Veluchamy, A, Ballerini, L, Vitart, V, Schraut, KE, Kirin, M, Campbell, H, Joshi, P, Relan, D, Harris, S, Brown, E, Vaidya, SS, Dhillon, B, Zhou, K, Pearson, ER, Hayward, C, Polasek, O, Deary, I , MacGillivray, T , Wilson, J, Trucco, E, Palmer, CNA & Doney, ASF 2019, 'A novel genetic locus influencing retinal venular tortuosity is also associated with risk of coronary artery disease', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 39, no. 12, pp. 2542-2552. https://doi.org/10.1161/ATVBAHA.119.312552

TY - JOUR

T1 - A novel genetic locus influencing retinal venular tortuosity is also associated with risk of coronary artery disease

AU - Veluchamy, Abirami

AU - Ballerini, Lucia

AU - Vitart, Veronique

AU - Schraut, Katharina E

AU - Kirin, Mirna

AU - Campbell, Harry

AU - Joshi, Peter

AU - Relan, Devanjali

AU - Harris, Sarah

AU - Brown, Ellie

AU - Vaidya, Suraj S

AU - Dhillon, Baljean

AU - Zhou, Kaixin

AU - Pearson, Ewan R

AU - Hayward, Caroline

AU - Polasek, Ozren

AU - Deary, Ian

AU - MacGillivray, Tom

AU - Wilson, James

AU - Trucco, Emmanuele

AU - Palmer, Colin N. A.

AU - Doney, Alexander S. F.

PY - 2019/12

Y1 - 2019/12

N2 - 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 (Ntotal=1413). In the combined analysis of discovery and replication cohorts, the lead single-nucleotide polymorphism in ACTN4/CAPN12 was rs1808382 (βs.d.=-0.109; SE=0.015; P=2.39×10-13) and in COL4A2 was rs7991229 (βs.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.

AB - 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 (Ntotal=1413). In the combined analysis of discovery and replication cohorts, the lead single-nucleotide polymorphism in ACTN4/CAPN12 was rs1808382 (βs.d.=-0.109; SE=0.015; P=2.39×10-13) and in COL4A2 was rs7991229 (βs.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.

KW - atrial fibrillation

KW - biomarkers

KW - cardiovascular diseases

KW - genome-wide association study

KW - heart rate

UR - https://www.ahajournals.org/doi/suppl/10.1161/ATVBAHA.119.312552

U2 - 10.1161/ATVBAHA.119.312552

DO - 10.1161/ATVBAHA.119.312552

M3 - Article

SN - 1079-5642

VL - 39

SP - 2542

EP - 2552

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 12

ER -

A novel genetic locus influencing retinal venular tortuosity is also associated with risk of coronary artery disease

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

Other files and links

Fingerprint

The Disconnected Mind Phase 3

Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

A genome wide association study of non pathological cognitive ageing

Cite this

A novel genetic locus influencing retinal venular tortuosity is also associated with risk of coronary artery disease

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

Other files and links

Fingerprint

Projects

The Disconnected Mind Phase 3

Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

A genome wide association study of non pathological cognitive ageing

Cite this