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Louis R. Pasquale, Vincent Laville, Hugo Aschard, Adriana I Iglesias, Jae H Kang, David Mackey, Veronique Vitart, Cornelia van Duijn, Jonathan L Haines, Janey L Wiggs; Shared genetic effects between diabetes-related traits and glaucoma-related traits. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5144.
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Evidence suggests adverse relations between diabetes-related traits and primary open-angle glaucoma (POAG) or glaucoma related traits such as intraocular pressure (IOP), but some prior studies may have been susceptible to various biases. Thus, we undertook an agnostic cross-trait genomic approach to explore these relationships.
We assembled publically available genome-wide summary statistics from European-derived Caucasians on type 2 diabetes (T2D) and related traits (2 hour glucose (2HG), fasting blood sugar, hemoglobin A1c (HbA1c), insulin resistance, body mass index, triglycerides (TG), low density lipoproteins (LDL), and high density lipoproteins (HDL)). We collected similar data for POAG and related traits (central corneal thickness, IOP, and cup-disc ratio (CDR)) in the NEIGHBORHOOD consortium and the International Glaucoma Genetics Consortium. We calculated both genetic heritabilty (h2) and cross-trait correlation (rg) using the LD score regression method (Bulik-Sullivan et al.,Nature Genetics 2015).
The percent variance of each trait explained by genetic effects (h2) ± standard error (SE)) was 10%±1% for T2D, 7%±2% for POAG and 6%±1% for IOP (range for other traits: 3%±1% [2HG] to 35%±4% [CDR]). Overall, there was little rg between diabetes-related traits and glaucoma-related traits. The rg±SE between T2D and IOP and between T2D and POAG were 15%±9% (p=0.12) and -14%±10% (p=0.16), respectively. There were no significant rg between T2D related traits and glaucoma traits, except for a surprisingly negative rg between HbA1c and POAG (rg=-31%± 14%; p=0.02). We also found borderline significant rg between LDL and IOP (16%±8%; p=0.05) . The overall non-significant rg between T2D, POAG and IOP were likely not related to low statistical power, as the sample size for genome-wide data used for the main outcomes ranged from 27,558 (IOP) to 149,821 (T2D). Also, as positive controls, we observed high rg between blood lipid traits and T2D (e.g., the rg between TG and T2D was 34%±6% (p=4.6E-08)) and between glaucoma-related traits, such as CDR or IOP, and POAG (57%±9%, p=2.8E-10 and 43%±13%, p=6.0E-04, respectively).
These findings, which contain adequate internal positive controls, suggest that there is limited shared genetic effects between diabetes-related traits and glaucoma-related traits.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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