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Edward Bloch, Ekaterina Hristova Yonova, Eneh JONES-ODEH, Katie Williams, Diana Kozareva, Christopher J Hammond; Genetic and environmental factors influencing the ganglion cell complex in a healthy aging British cohort. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
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 afffecting GCC in the general population. We performed a cross-sectional twin cohort study to investigate the heritability and to explore epidemiological and ophthalmic factors influencing GCC.
GCC thickness (Optovue iVue SD-OCT), autorefraction and intraocular pressure (IOP) measurements (Visionix120, The Luneau Technology group) were obtained in 873 subjects of European ancestry without ocular pathology from the TwinsUK cohort. Blood pressure, body mass index and standard blood tests were measured. Glomerular filtration rate (GFR) estimated using the MDRD formula.Associations between GCC thickness and age, sex, spherical equivalent (SpheE), IOP, BMI, mean arterial pressure (MAP), blood markers, eGFR and diabetes status were assessed using univariate and multivariate stepwise linear regression models. In all models family structure was taken into account.Heritability analyses were performed on 692 twins (197MZ and 149DZ pairs using maximum likelihood structural equation twin modeling implemented in the OpenMx package.
The mean age of the cohort was 60.9 years (SD 11.7, range 19.2-89.2) with a strong female preponderance (93%). The average inner GCC thickness was 95.3μm (57.7-119.6, SD 7.4).In multivariable modeling, the average inner GCC thickness was independently associated with age (β=-0.12, p<0.001) and SpheE (β=0.65, p<0.001) but not with sex, IOP, BMI, MAP or diabetes (p>0.05). From the blood parameters, higher eGFR was associated with increase in GCC thickness (β=0.07, p<0.001). In other exploratory analyses, albumin and alkaline phosphatase were independently associated with average inner GCC thickness (p=0.01 and p=0.005 respectively).GCC was highly heritable with additive genetic effects explaining 87% (95%CI: 84-90) of phenotypic variance and individual environmental effects explained the remaining 13% (95%CI: 10-16).
GCC appears to be highly heritable; identification of genes may help understanding of glaucoma biological pathways. Our data suggest it is important to take into account age and refractive error when using GCC thickness as a diagnostic tool. Further research is required to explore the relationship between GCC and renal function identified by this study.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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