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

Laville, Vincent; Kang, Jae H.; Cousins, Clara C; Iglesias, A.; Nagy, Réka; Bailey, Jessica N. Cooke; Igo, Robert P.; Song, Yeunjoo E.; Chasman, Daniel I.; Christen, William G.; Kraft, Peter; Rosner, Bernard; Hu, Frank B.; Wilson, James F.; Gharahkhani, Puya; Hewitt, Alex W.; Mackey, David A.; Hysi, Pirro G.; Hammond, Christopher J; vanDuijn, C.M.; Haines, Jonathan L.; Vitart, Véronique; Fingert, John H.; Hauser, Michael A.; Aschard, Hugues; Wiggs, Janey L.; Khawaja, Anthony P.; MacGregor, Stuart; Pasquale, Louis R.; Biobank, UK

doi:10.1016/j.ajo.2019.05.015

Cited by 15 publications

(11 citation statements)

References 66 publications

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“…Eight of the POAG loci did not appear to have a clear effect on IOP or VCDR, although a small effect on glaucoma via a small change in IOP or VCDR could not be ruled out. The overall correlation of effect sizes between all POAG risk loci and IOP was 0.53, and between POAG and VCDR was 0.31, in line with previously published genetic correlation estimates 25 . To better visualize clustering of the POAG SNPs based on their effect on IOP/VCDR, we created a heatmap by clustering SNPs based on Pearson correlation between effect estimates of SNPs on POAG, IOP, and VCDR (Supplementary Fig.…”

Section: Resultssupporting

confidence: 89%

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

2021

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Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

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Section: Resultssupporting

confidence: 89%

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

2021

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“… 20 , 21 To what extent an IOP PRS captures a family history of glaucoma is unknown. The variance of corneal-compensated IOP in the UK Biobank explained by GWAS SNPs 46 and the IOP PRS is approximately 15% and 4%, respectively.…”

Section: Discussionmentioning

confidence: 98%

Intraocular Pressure, Glaucoma, and Dietary Caffeine Consumption

et al. 2021

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Purpose: We examined the association of habitual caffeine intake with intraocular pressure (IOP) and glaucoma and whether genetic predisposition to higher IOP modified these associations. We also assessed whether genetic predisposition to higher coffee consumption was related to IOP.Design: Cross-sectional study in the UK Biobank.Participants: We included 121 374 participants (baseline ages, 39e73 years) with data on coffee and tea intake (collected 2006e2010) and corneal-compensated IOP measurements in 2009. In a subset of 77 906 participants with up to 5 web-based 24-hour-recall food frequency questionnaires (2009e2012), we evaluated total caffeine intake. We also assessed the same relationships with glaucoma (9286 cases and 189 763 controls).Methods: We evaluated multivariable-adjusted associations with IOP using linear regression and with glaucoma using logistic regression. For both outcomes, we examined geneediet interactions using a polygenic risk score (PRS) that combined the effects of 111 genetic variants associated with IOP. We also performed Mendelian randomization using 8 genetic variants associated with coffee intake to assess potential causal effects of coffee consumption on IOP.Main Outcome Measures: Intraocular pressure and glaucoma.Results: Mendelian randomization analysis did not support a causal effect of coffee drinking on IOP (P > 0.1). Greater caffeine intake was associated weakly with lower IOP: the highest (!232 mg/day) versus lowest (<87 mg/day) caffeine consumption was associated with a 0.10-mmHg lower IOP (P trend ¼ 0.01). However, the IOP PRS modified this association: among those in the highest IOP PRS quartile, consuming > 480 mg/day versus < 80 mg/day was associated with a 0.35-mmHg higher IOP (P interaction ¼ 0.01). The relationship between caffeine intake and glaucoma was null (P ! 0.1). However, the IOP PRS also modified this relationship: compared with those in the lowest IOP PRS quartile consuming no caffeine, those in the highest IOP PRS quartile consuming ! 321 mg/day showed a 3.90-fold higher glaucoma prevalence (P interaction ¼ 0.0003).Conclusions: Habitual caffeine consumption was associated weakly with lower IOP, and the association between caffeine consumption and glaucoma was null. However, among participants with the strongest genetic predisposition to elevated IOP, greater caffeine consumption was associated with higher IOP and higher glaucoma prevalence. Ophthalmology 2020;-:1e11

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“…Nevertheless, the link between diabetes and POAG-related traits, including IOP, remains controversial in recent findings from genome-wide association studies [57][58][59] . Although Shiga et al found a significant positive correlation between diabetes and POAG in a Japanese population 57 , another Japanese genetic study 58 and a study in Europeans 59 found no such association.…”

Section: Discussionmentioning

confidence: 99%

Relationships of diabetes and hyperglycaemia with intraocular pressure in a Japanese population: the JPHC-NEXT Eye Study

Hanyuda

Sawada

Yuki

et al. 2020

Sci Rep

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Although a meta-analysis previously suggested a positive relationship between diabetes and intraocular pressure (IOP), the interrelationships among diabetes, IOP, and other ocular biometric parameters remain unclear. The present study investigated the relationships of diabetes, haemoglobin A1c (HbA1c), and serum glucose with IOP and ocular hypertension (IOP > 21 mmHg) in non-glaucomatous Japanese adults living in Chikusei City. Diabetes was defined as a self-reported history of diabetes, the use of antidiabetic medication, or HbA1c levels ≥6.5%. Among 6,786 enrolled participants aged 40 years and above, 734 were classified as diabetic (10.8%). After adjusting for several confounders, the IOP values were significantly higher in participants with diabetes than in those without diabetes (14.4 ± 0.1 vs. 13.9 ± 0.1 mmHg, P < 0.001) and were also significantly increased in those with elevated HbA1c and serum glucose levels (both P < 0.001). Moreover, diabetes was significantly related to ocular hypertension (multivariable-adjusted odds ratio, 1.75; 95% confidence interval, 1.09–2.81; P < 0.05). The positive influence of diabetes with ocular hypertension was consistent even after adjustment for central corneal thickness. In conclusion, diabetes, elevated HbA1c, and increased serum glucose are significant contributing factors for elevated IOP.

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

Cited by 15 publications

References 66 publications

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

Intraocular Pressure, Glaucoma, and Dietary Caffeine Consumption

Relationships of diabetes and hyperglycaemia with intraocular pressure in a Japanese population: the JPHC-NEXT Eye Study

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