Genetic regions associated with corneal thickness identified by Kaiser Permanente researchers
Study offers insights into eye disease risk, particularly for African Americans
By Jan Greene
A new Kaiser Permanente study identifies regions of the human genome related to central corneal thickness (CCT), offering new insights into risk for certain eye diseases. The research finds people with greater African ancestry are more likely to have thinner corneas, which could put them at risk for the progressive eye disease keratoconus.
The study was published June 11 in the journal Communications Biology.
The researchers analyzed genetic data from Kaiser Permanente Northern California patients who provided DNA samples as participants in the Genetic Epidemiology Research on Adult Health and Aging (GERA) project (now part of the Kaiser Permanente Research Bank). This is the first genetic study of CCT that includes individuals of African and Hispanic/Latino ancestry; this was possible because the GERA study population contains more information from people of those backgrounds and about CCT than do other biobanks.
The investigators looked for both genetic insights and biological pathways to better understand corneal thickness variation between individuals and its relationship with vision disorders such as primary open-angle glaucoma and keratoconus, which can both lead to vision loss.
They found a genetic correlation between CCT and keratoconus, and also a link between CCT variation and African ancestry. They did not find a direct link between keratoconus and being African American, though other studies have suggested it. Keratoconus is a disease that changes the cornea’s shape and can require a cornea transplant in severe cases.
“This is the first study of genetic associations with CCT among African American and Hispanic people,” said lead author Helene Choquet, PhD, staff scientist with the Kaiser Permanente Division of Research. “For African Americans, we found greater African ancestry is associated with a thinner CCT in comparison to European ancestry. This is the first time this has been demonstrated.”
The study used data on 44,039 individuals in the GERA cohort and the International Glaucoma Genetics Consortium. The analysis identified 98 regions, or “loci,” across the human genome that were strongly associated with CCT, 41 of them newly discovered. Of these, 20 were also strongly associated with the risk of keratoconus. The loci identified by this study account for about 14% of the variation in CCT and “largely explain the genetic ancestry association of thinner CCT observed in African Americans,” the authors wrote.
Another important insight from this research is that thinner corneas may not be a causal risk factor for glaucoma, said coauthor Eric Jorgensen, PhD, a research scientist with the Division of Research. Thinner central corneal thickness is a factor included in some glaucoma prediction models, but maybe it shouldn’t be, Jorgensen said. “We know that African Americans are at higher risk of glaucoma and there was a chance that was because they are more likely to have thinner corneas on average. What we find is that’s not the case.” There may be other biological mechanisms at play, he said.
Coauthor Ronald Melles, MD, an ophthalmologist with The Permanente Medical Group, said the findings are nuanced for clinicians. “Ophthalmologists measure corneal thickness during the evaluation of glaucoma patients because we believe it may help us identify individuals with thin corneas who are at greater risk for progressive visual loss,” Melles said. “The results of this study suggest that the relationship between corneal thickness and glaucoma is more complicated than we thought.”
The study was funded by the National Institutes of Health, and the National Eye Institute; the GERA cohort work was also supported by the Robert Wood Johnson Foundation, the Wayne and Gladys Valley Foundation, the Ellison Medical Foundation, and Kaiser Permanente Community Benefit programs.
Coauthors included Jie Yin, MS, Khanh K. Thai, MS, and Catherine Schaefer, PhD, of the Division of Research; Neil Risch, PhD, Thomas J. Hoffman, PhD, Mark N. Kvale, PhD, and Yambazi Banda, PhD, K. Saidas Nair, PhD, and M. Maria Glymour, ScD of the University of California, San Francisco; Alison J. Hardcastle, PhD, of University College London; Stephen J. Tuft, MD, FRACS, of Moorfields Eye Hospital in London; and Pirro G. Hysi, MD, PhD, of King’s College London.
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About the Kaiser Permanente Division of Research
The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and society at large. It seeks to understand the determinants of illness and well-being, and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 600-plus staff is working on more than 450 epidemiological and health services research projects. For more information, visit divisionofresearch.kaiserpermanente.org or follow us @KPDOR.
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