7 genetic risk factors found to be associated with common eye disorder

March 04, 2013

A professor from Case Western Reserve University School of Medicine is one of the lead authors of a study identifying seven new regions of the human genome that are associated with increased risk of age-related macular degeneration (AMD), a leading cause of blindness among older adults.

The AMD Gene Consortium, a network of international investigators representing 18 research groups, also confirmed the existence of 12 other regions - called loci - that had been identified in previous studies. The authors report their findings online in the journal Nature Genetics. Supported by the National Eye Institute (NEI), a part of the National Institutes of Health, the study represents the most comprehensive genome-wide analysis of genetic variations associated with AMD.

"This work represents a big step forward toward solving why some people get AMD, while others do not," said Sudha Iyengar, PhD, professor of epidemiology and biostatistics at Case Western Reserve School of Medicine and a member of the consortium's senior executive committee. "This disease is not caused by a single change in the DNA, but represents many events that accumulate over the lifetime of a patient. Identification of these genes provides molecular windows into the AMD disease process."

AMD affects the macula, a region of the retina responsible for central vision. The retina is the layer of light-sensitive tissue in the back of the eye that houses rod and cone photoreceptor cells. Compared with the rest of the retina, the macula is especially dense with cone photoreceptors; humans rely on the macula for tasks that require sharp vision, such as reading, driving, and recognizing faces. As AMD progresses, such tasks become more difficult and eventually impossible. Some kinds of AMD are treatable, but no cure exists. An estimated 2 million Americans suffer from AMD.

Since the 2005 discovery that certain variations in the gene for complement factor H--a component of the immune system--are associated with major risk for AMD, research groups around the world have conducted genome-wide association studies to identify other loci that affect AMD risk. These studies were made possible by tools developed through the Human Genome Project, which mapped human genes, and related projects, such the International HapMap Project, which identified common patterns of genetic variation within the human genome.

The consortium's analysis included data from more than 17,100 people with the most advanced and severe forms of AMD, which were compared to data from more than 60,000 people without AMD. The 19 loci that were found to be associated with AMD implicate a variety of biological functions, including regulation of the immune system, maintenance of cellular structure, growth and permeability of blood vessels, lipid metabolism, and atherosclerosis.

As with other common diseases, such as Type 2 diabetes, an individual person's risk for getting AMD is likely determined not by one but many genes. Further comprehensive DNA analysis of the areas around the 19 loci identified by the AMD Gene Consortium could turn up undiscovered rare genetic variants with a disproportionately large effect on AMD risk. Discovery of such genes could greatly advance scientists' understanding of AMD pathogenesis and their quest for more effective treatments.

"This compelling analysis by the AMD Gene Consortium demonstrates the enormous value of effective collaboration," said NEI director Paul A. Sieving, MD, PhD. "Combining data from multiple studies, this international effort provides insight into the molecular basis of AMD, which will help researchers search for causes of the disease and will inform future development of new diagnostic and treatment strategies."
Other lead authors of the study include: Gonçalo R. Abecasis, D. Phil., University of Michigan; Lindsay A. Farrer, PhD, Boston University; Iris Heid, PhD, University of Regensburg, Germany; and Jonathan L. Haines, PhD, Vanderbilt University.

For more information about AMD, visit http://www.nei.nih.gov/health/maculardegen/index.asp.

This research was supported in part by the NEI Intramural Research Program and NIH grants Z01EY000475, U10EY006594, R01EY015810, R01EY015286, R03EY013438, R01EY010605, R24EY017404, R01EY014458, R01EY017362, R24EY017404, R01EY013834, K23EY000365, R01EY009611, R01EY021532, R01EY021163, R01EY013435, R24EY019861, P30EY019007, T32EY021453, R01EY012118, R01EY022005, R01EY016862, R01EY014467, K12EY16335, R01EY11309, R01EY09859, R01EY014428, R01EY018660, R01EY019270, U54HG006542, P01CA87969, R01CA49449, and R01HL35464.

About Case Western Reserve University School of Medicine

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.

Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu

Case Western Reserve University

Related Human Genome Articles from Brightsurf:

240 mammals help us understand the human genome
A large international consortium led by scientists at Uppsala University and the Broad Institute of MIT and Harvard has sequenced the genome of 130 mammals and analysed the data together with 110 existing genomes to allow scientist to identify which are the important positions in the DNA.

The National Human Genome Research Institute publishes new vision for human genomics
The National Human Genome Research Institute this week published its 'Strategic vision for improving human health at The Forefront of Genomics' in the journal Nature.

Interpreting the human genome's instruction manual
Berkeley Lab bioscientists are part of a nationwide research project, called ENCODE, that has generated a detailed atlas of the molecular elements that regulate our genes.

3-D shape of human genome essential for robust inflammatory response
The three-dimensional structure of the human genome is essential for providing a rapid and robust inflammatory response but is surprisingly not vital for reprogramming one cell type into another.

The genome of chimpanzees and gorillas could help to better understand human tumors
A new study by researchers from the Institute of Evolutionary Biology (IBE), a joint center of UPF and the Spanish National Research Council (CSIC), shows that, surprisingly, the distribution of mutations in human tumors is more similar to that of chimpanzees and gorillas than that of humans.

It's in our genome: Uncovering clues to longevity from human genetics
Researchers from Osaka University found that high blood pressure and obesity are the strongest factors reducing lifespan based on genetic and clinical information of 700,000 patients in the UK, Finland and Japan.

New limits to functional portion of human genome reported
An evolutionary biologist at the University of Houston has published new calculations that indicate no more than 25 percent of the human genome is functional.

Synthesizing the human genome from scratch
For the past 15 years, synthetic biologists have been figuring out how to synthesize an organism's complete set of DNA, including all of its genes.

Science and legal experts debate future uses and impact of human genome editing in Gender & the Genome
Precise, economical genome editing tools such as CRISPR have made it possible to make targeted changes in genes, which could be applied to human embryos to correct mutations, prevent disease, or alter traits.

Evolution purged many Neanderthal genes from human genome
Neanderthal genetic material is found in only small amounts in the genomes of modern humans because, after interbreeding, natural selection removed large numbers of weakly deleterious Neanderthal gene variants, according to a study by Ivan Juric and colleagues at the University of California, Davis, published Nov.

Read More: Human Genome News and Human Genome Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.