Kaiser Permanente analysis finds 37 new locations on human genome related to the common eye disease
Using data from Kaiser Permanente and United Kingdom biobanks, researchers have identified new locations on the human genome that could relate to the risk of age-related cataract. Their findings were published June 14 in Nature Communications.
The study also found a location on the genome that appears to be specific to the risk of cataract in women only, which may explain in part why cataracts are more common in women.
A better understanding of the genetic underpinnings of cataract can lead to the development of tests to identify individuals at greater risk so they can get earlier treatment, said lead author Hélène Choquet, PhD, a research scientist at the Kaiser Permanente Division of Research.
“This is the first step, and we can use this information along with other factors to build predictive models to identify people more likely to develop cataract,” Choquet said. “If we can screen people before they develop disease that would help them and their doctors to quickly identify when a cataract is forming.”
The data could also be used to develop molecular targets for non-surgical treatments, she added.
Cataracts can be caused by aging, injury, disease, use of certain medications or smoking, and can lead to progressive loss of vision. Researchers believe there is a strong role for genetics in risk for developing age-related cataract. There are also congenital cataracts that can occur in younger people, but this study focused on age-related cataract, the most common type.
The study was a genome-wide association meta-analysis (GWAS) that found 54 locations on the human genome related to cataract, 37 of them for the first time. The analysis looked at genetics and health records for 67,844 people with cataract and 517,399 cataract-free control patients. The authors said it was the largest and most ethnically diverse genetic study of cataract susceptibility to date.
The data came from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, a group of more than 100,000 Kaiser Permanente Northern California members who volunteered their genetic and medical information for research. GERA is part of the Kaiser Permanente Research Program on Genes, Environment and Health, which is itself part of the Kaiser Permanente Research Bank. Researchers also used data from the UK Biobank, which contains genetic and health information from about a half million residents of the United Kingdom, and confirmed their findings using data from genetics firm 23andMe.
Along with analyzing the genome data from the people in the 3 databases, the researchers were also able to confirm their findings using a separate database of information about gene expression in mouse eye lens tissue at various stages of development. The Integrated Systems Tool for Eye gene discovery (iSyTE) data demonstrated that many cataract candidate genes within the new identified locations were robustly expressed in the mouse lens, offering supporting evidence for their relevance to lens development and cataract pathophysiology.
“If the gene is expressed in the tissue that means it could have a direct relationship to the development of a cataract, which is caused by crystallization of the lens,” Choquet said. “It’s comforting to know we found 80% of the genes in our study expressed in eye tissue.”
Co-author Ronald B. Melles, MD, an ophthalmologist with The Permanente Medical Group, noted that cataracts are the leading cause of blindness worldwide, with almost 4 million cataract operations performed each year in the U.S. alone. “It was exciting to participate in research that has provided us with new biological insights into this common vision problem,” Melles said.
The study was funded by various grants from the National Institutes of Health, and in particular the National Eye Institute.
Co-authors also included Jie Yin, MS, of the Division of Research; Eric Jorgenson, PhD, formerly of the Division of Research; Deepti Anand, PhD and Salil A. Lachke, PhD, of the University of Delaware; Gabriel Cuellar-Partida, PhD, Wei Wang, PhD, and the 23andMe Research Team of 23andMe Inc.; Thomas J. Hoffmann, PhD, and K Saidas Nair, PhD, of the University of California, San Francisco; and Pirro G. Hysi, MD, PhD, of King’s College London.
Read more about this research and collaborators at the University of Delaware
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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.