Genes associated with age-related macular degeneration (AMD) differ in patients with African ancestry compared to those with European ancestry, according to a study.
AMD is less prevalent and milder in Black populations than in White populations and genetic research on AMD has historically focussed on White or Asian populations, according to study coauthor Dr Neal Peachey, from the Cleveland Clinic Cole Eye Institute in the United States.
The study, published in Nature Genetics,1 is the first to assess disease across ancestral populations, including people with African or Hispanic heritage.
The investigators worked with the US Department of Veterans Affairs’ Million Veteran Program, which was launched in 2011 to research health in US veterans recruited at more than 70 Veterans Affairs medical centres.
“Thanks to this huge number of study participants, we were able to perform the largest genome wide meta-analysis on AMD to date,” Dr Peachey said.
“It’s also the first multi-ancestry AMD study. Ancestry is an important factor that has been overlooked in some genetic studies. We were able to not only address that gap but also demonstrate that ancestry is a critical factor in AMD.”
Earlier research on genetic risk factors for AMD implicated the CFH (and other genes associated with the complement pathway) and ARMS2/HTRA1 genes.
Dr Peachey said his study found that while CFH and ARMS2/HTRA1 are highly associated with AMD in people with European ancestry, the genes are less associated in people with Hispanic ancestry and not associated in people with African ancestry.
He said an additional 30 genes have been associated with AMD, including the HLA-DQB1 gene, which is more significant for patients with African or Hispanic ancestries.
“Those genetic signals probably were there all along, but we were able to identify them now thanks to pooling our Million Veteran Program data with data from other groups worldwide,” Dr Peachey said in a news release.2
Certain demographic and phenotypic features increase risk for AMD, including being female, drinking alcohol, and smoking.
“By far, the most important finding was the differing risk profiles among ancestry groups,” Dr Peachey said.
“We now have a lot more research to do to figure out what’s going on. Why are the genes that are so strongly associated with AMD in one group not associated with the disease in another?
“Based on findings from earlier genetic studies, treatments are being developed for AMD that target the complement signalling pathway,” he said.
“But now we know that those treatments are unlikely to be effective in people for whom that pathway isn’t a genetic risk factor. Future treatment trials should consider patients’ genetic risk factors.”
References
- Gorman BR, Voloudakis G, Zhang W et al; VA Million Veteran Program; International AMD Genomics Consortium (IAMDGC); Hadi T, Anger MD, Iyengar SK, et al. Genome-wide association analyses identify distinct genetic architectures for age-related macular degeneration across ancestries. Nat Genet. 2024 Dec;56(12):2659-2671. doi: 10.1038/s41588-024-01764-0.
- Cleveland Clinic, Study is first to reveal that genes causing AMD vary by ancestry, available at: consultqd.clevelandclinic.org/study-is-first-to-reveal-that-genes-causing-amd-vary-by-ancestry [accessed April 2025].
