Genetic Correlations Between Diabetes and Glaucoma: An Analysis of Continuous and Dichotomous Phenotypes

Vincent Laville; Jae H Kang; Clara Cousins; Adriana Iglesias; Réka Nagy; Jessica Cooke Bailey; Robert Igo Jr; Yeunjoo Song; Daniel Chasman; William Christen; Peter Kraft; Bernard Rosner; Frank Hu; James Wilson; Puya Gharahkhani; Alex Hewitt; David Mackey; Pirro Hysi; Christopher Hammond; Cornelia vanDuijn; Jonathan Haines; Veronique Vitart; John Fingert; Michael Hauser; Hugues Aschard; Janey Wiggs; Anthony Khawaja; Stuart Macgregor; Louis Pasquale; International Glaucoma Genetics Consortium

doi:10.1016/j.ajo.2019.05.015

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Genetic Correlations Between Diabetes and Glaucoma: An Analysis of Continuous and Dichotomous Phenotypes

Journal article

Peer reviewed

Genetic Correlations Between Diabetes and Glaucoma: An Analysis of Continuous and Dichotomous Phenotypes

Vincent Laville, Jae H Kang, Clara Cousins, Adriana Iglesias, Réka Nagy, Jessica Cooke Bailey, Robert Igo Jr, Yeunjoo Song, Daniel Chasman, William Christen, …

American journal of ophthalmology, Vol.206, pp.245-255

10/2019

DOI: 10.1016/j.ajo.2019.05.015

PMCID: PMC6864262

PMID: 31121135

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Abstract

PurposeA genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes- and glaucoma-related traits.DesignCross-sectional study.MethodsWe assembled genome-wide association study summary statistics from European-derived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure [IOP], central corneal thickness [CCT], corneal hysteresis [CH], corneal resistance factor [CRF], cup-to-disc ratio [CDR], and primary open-angle glaucoma [POAG]). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank, and the International Glaucoma Genetics Consortium. We calculated genetic correlation (rg) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT, and select diabetes-related traits based on individual level phenotype data in 2 Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines.ResultsOverall, there was little rg between diabetes- and glaucoma-related traits. Specifically, we found a nonsignificant negative correlation between T2D and POAG (rg = −0.14; P = .16). Using Sequential Oligogenic Linkage Analysis Routines, the genetic correlations between measured IOP, CCT, FBS, fasting insulin, and hemoglobin A1c were null. In contrast, genetic correlations between IOP and POAG (rg ≥ 0.45; P ≤ 3.0 × 10−4) and between CDR and POAG were high (rg = 0.57; P = 2.8 × 10−10). However, genetic correlations between corneal properties (CCT, CRF, and CH) and POAG were low (rg range −0.18 to 0.11) and nonsignificant (P ≥ .07).ConclusionThese analyses suggest that there is limited genetic correlation between diabetes- and glaucoma-related traits.

Bioinformatics

Computer Science

Europe

Genetics

Life Sciences

Phenotype

Statistics

United States

Adolescent

Adult

Aged

Aged, 80 and over

Applications

Cross-Sectional Studies

Diabetes Mellitus, Type 2

Female

Genome-Wide Association Study

Glaucoma, Open-Angle

Human genetics

Humans

Incidence

Intraocular Pressure

Male

Methodology

Middle Aged

Pedigree

Santé publique et épidémiologie

Tonometry, Ocular

Young Adult

Details

Title: Subtitle: Genetic Correlations Between Diabetes and Glaucoma: An Analysis of Continuous and Dichotomous Phenotypes
Creators: Vincent Laville - Pasteur Institute
Jae H Kang - Brigham and Women's Hospital
Clara Cousins - Massachusetts Eye and Ear Infirmary
Adriana Iglesias - Erasmus University Rotterdam
Réka Nagy - University of Edinburgh
Jessica Cooke Bailey - Case Western Reserve University
Robert Igo Jr - Case Western Reserve University
Yeunjoo Song - Case Western Reserve University
Daniel Chasman - Brigham and Women's Hospital
William Christen - Brigham and Women's Hospital
Peter Kraft - Harvard University
Bernard Rosner - Harvard University
Frank Hu - Harvard University
James Wilson - University of Edinburgh
Puya Gharahkhani - QIMR Berghofer Medical Research Institute
Alex Hewitt - The University of Melbourne
David Mackey - The University of Western Australia
Pirro Hysi - King's College London
Christopher Hammond - King's College London
Cornelia vanDuijn - University of Oxford
Jonathan Haines - Case Western Reserve University
Veronique Vitart - University of Edinburgh
John Fingert - University of Iowa
Michael Hauser - Duke University
Hugues Aschard - Harvard University
Janey Wiggs - Massachusetts Eye and Ear Infirmary
Anthony Khawaja - University of Cambridge
Stuart Macgregor - QIMR Berghofer Medical Research Institute
Louis Pasquale - Icahn School of Medicine at Mount Sinai
International Glaucoma Genetics Consortium
Resource Type: Journal article
Publication Details: American journal of ophthalmology, Vol.206, pp.245-255
DOI: 10.1016/j.ajo.2019.05.015
PMID: 31121135
PMCID: PMC6864262
NLM abbreviation: Am J Ophthalmol
ISSN: 0002-9394
eISSN: 1879-1891
Publisher: Elsevier Masson
Grant note: DOI: 10.13039/100000053, name: National Eye Institute, award: EY015473, P30 EY014104, EY022305; name: Moorfields Eye Charity; DOI: 10.13039/501100000923, name: Australian Research Council; DOI: 10.13039/501100000925, name: National Health and Medical Research Council, award: 1150144, 1116360
Language: English
Date published: 10/2019
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9984180935702771

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