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Genetic and Environmental Factors Associated With the Ganglion Cell Complex in a Healthy Aging British Cohort

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
JournalJAMA Ophthalmology
Early online date17 Nov 2016
DOIs
Accepted/In press28 Sep 2016
E-pub ahead of print17 Nov 2016

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Abstract

Importance: Measurement of ganglion cell complex (GCC) thickness may be more sensitive than current methods for glaucoma diagnosis and research. However, little is known about the factors influencing GCC thickness in the general population.

Objectives: To investigate the heritability of and factors associated with GCC thickness in a healthy aging population.

Design, Setting, and Participants: A cross-sectional twin study was conducted from August 27, 2014, to March 31, 2016, among 1657 participants of white British ancestry from the TwinsUK study cohort without ocular pathologic conditions. Heritability analyses were conducted in 1432 twins (426 monozygous and 290 dizygous pairs). Association analyses were performed using univariable and multivariable stepwise linear regression models, taking family structure into account. Heritability analyses were conducted using maximum likelihood structural equation twin modeling.

Main Outcomes and Measures: Parameters measured included GCC thickness, autorefraction, intraocular pressure, blood pressure, body mass index, and cholesterol, creatinine, glucose, insulin, triglycerides, and urea levels. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula.

Results: Among the 1657 participants (mean [SD] age, 56.0 [15.3] years; 89.5% women and 10.5% men), the mean [SD] inner GCC thickness was 96.0 [7.6] μm (95% CI, 95.1-96.2). In multivariable modeling, the mean inner GCC thickness was associated with advancing age (β, -0.14; P < .001), increased body mass index (β, -0.15; P = .001), spherical equivalent (β, 0.70; P < .001), and higher estimated glomerular filtration rate (β, 0.03; P = .02). A 1-U increase in age or body mass index was associated with a 0.14-µm and 0.15-µm decrease in GCC thickness, respectively (P < .001), while a 1-U increase in spherical equivalent or estimated glomerular filtration rate was associated with a 0.70-µm (P < .001) and 0.03-µm (P = .02) increase in GCC thickness, respectively. Ganglion cell complex thickness was not associated with sex, intraocular pressure, or diabetes. Age-adjusted GCC thickness was highly heritable, with additive genetic effects explaining 81% (95% CI, 78%-84%) of phenotypic variance and individual environmental factors explaining the remaining 19% (95% CI, 16%-22%).

Conclusions and Relevance: Ganglion cell complex thickness appears to be highly heritable and further genetic analysis may help identify new biological pathways for glaucoma. The results suggest it may be important to account for age, body mass index, refractive error, and sex when using GCC thickness as a diagnostic tool. Replication of their results is required, as is further research to explain the association between renal function and GCC thickness.

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