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

被引：12

作者：

Laville, Vincent ^{[1
]}

Kang, Jae H. ^{[2
]}

Cousins, Clara C. ^{[3
]}

Iglesias, Adriana I. ^{[4
,5
]}

Nagy, Reka ^{[6
]}

Bailey, Jessica N. Cooke ^{[6
,7
,8
]}

Igo, Robert P., Jr. ^{[7
]}

Song, Yeunjoo E. ^{[7
,8
]}

Chasman, Daniel I. ^{[9
]}

Christen, William G. ^{[9
]}

Kraft, Peter ^{[10
,11
]}

Rosner, Bernard A. ^{[2
,11
]}

Hu, Frank ^{[10
]}

Wilson, James F. ^{[6
,12
]}

Gharahkhani, Puya ^{[13
]}

Hewitt, Alex W. ^{[14
,15
]}

Mackey, David A. ^{[16
]}

Hysi, Pirro G. ^{[17
]}

Hammond, Christopher J. ^{[17
]}

Vanduijn, Cornelia M. ^{[4
,5
,18
]}

Haines, Jonathan L. ^{[7
,8
]}

Vitart, Veronique ^{[6
]}

Fingert, John H. ^{[19
]}

Hauser, Michael A. ^{[20
,21
]}

Aschard, Hugues ^{[1
,10
]}

Wiggs, Janey L. ^{[3
,12
]}

Khawaja, Anthony P. ^{[22
]}

Macgregor, Stuart ^{[13
]}

Pasquale, Louis R. ^{[2
,23
]}

机构：

[1] Inst Pasteur, Dept Computat Biol, Paris, France

[2] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA

[3] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA

[4] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands

[5] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

[6] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[7] Case Western Reserve Univ, Sch Med, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA

[8] Case Western Reserve Univ, Sch Med, Inst Computat Biol, Cleveland, OH 44106 USA

[9] Harvard Med Sch, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

[10] Harvard Med Sch, Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[11] Harvard Med Sch, Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[12] Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland

[13] QIMR Berghofer Med Res Inst, Stat Genet, Brisbane, Qld, Australia

[14] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic, Australia

[15] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia

[16] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Perth, WA, Australia

[17] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England

[18] Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England

[19] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA

[20] Duke Univ, Dept Ophthalmol, Durham, NC USA

[21] Duke Univ, Dept Med, Durham, NC USA

[22] Univ Cambridge, Sch Clin Med, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England

[23] Icahn Sch Med Mt Sinai, Dept Ophthalmol, One Gustave L Levy Pl,Box 1183, New York, NY 10029 USA

来源：

AMERICAN JOURNAL OF OPHTHALMOLOGY | 2019年 / 206卷

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

OPEN-ANGLE GLAUCOMA; LD SCORE REGRESSION; INTRAOCULAR-PRESSURE; RISK-FACTOR; CORNEAL THICKNESS; ASSOCIATION; MELLITUS; LOCI; HERITABILITY; GLUCOSE;

D O I：

10.1016/j.ajo.2019.05.015

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

PURPOSE: A 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. DESIGN: Cross-sectional study. METHODS: We 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 (r(g)) 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. RESULTS: Overall, there was little r g between diabetes- and glaucoma-related traits. Specifically, we found a nonsignificant negative correlation between T2D and POAG (r(g) = -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 (r(g) >= 0.45; P <= 3.0 x 10(-4)) and between CDR and POAG were high (r(g) = 0.57; P = 2.8 x 10(-10)). However, genetic correlations between corneal properties (CCT, CRF, and CH) and POAG were low (r(g) range -0.18 to 0.11) and nonsignificant (P >= .07). CONCLUSION: These analyses suggest that there is limited genetic correlation between diabetes- and glaucoma-related traits. (C) 2019 Elsevier Inc. All rights reserved.

引用

页码：245 / 255

页数：11

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