Genetic Markers of Asian Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older adults not only in developed countries but also increasingly in Asian countries, such as China, India, and Japan, primarily due to the rapidly changing demographics (an aging population) and lifestyle (obesity, diet, smoking) factors. While genetic factors are an important etiological agent in AMD, particularly in white Caucasian populations, it is unknown if the genes associated with AMD in Whites apply to Asians. The aim of this research project is thus to provide a further and new understanding of genetic factors for AMD in a multi-ethnic Asian population.

People with Caucasian ethnicity (white with European ancestry) have an increased risk for age-related macular degeneration (AMD). Many of the currently known risk genes were discovered by studying DNA from Caucasians. Using funds from a 2011 Macular Degeneration Research grant, Drs. Tien Yin Wong, Belinda Cornes, and collaborators will further characterize the genetic risks for AMD in Asians in its first major population-based study. They will compare the gene differences among people of three types of ethnicities (Chinese, Malay, and Indian) in Singapore, where people from these ethnic groups can have similar socioeconomic status and environmental exposures. The discovery of new risk genes for AMD may give clues to how this disease starts and progresses, and such insight may lead to prevention and treatments.

Progress Updates

The research of Dr. Wong’s and Dr. Cornes’ team involves three major ethnic groups in Singapore, including Chinese, Malays, and Indians. Genome-wide association studies (GWAS) of AMD genetic markers were performed on DNA samples from individuals from the three ethnic groups, adjusting for age, gender and population stratification (they grouped together people with similar backgrounds within each ethnic group). The team looked for patterns of similarity or difference within and between each grouping, but no new genes that reached genome-wide significances have so far been observed. The team’s initial GWAS analysis was limited by its power and are currently recruiting additional AMD cases to identify novel genes associated with Asian AMD by collaborating with other groups in Japan, Hong Kong, China and Korea to increase the sample size of the study. In this initial collaborative study, the team did not replicate previously reported association between rs1713985 at 4q12 and neovascular AMD, but confirmed the association between rs13278062 at 8p21 and neovascular AMD in Asian populations. The information obtained from this study is likely to help find new treatments, including gene therapy, for individuals with AMD from Singapore, other Asian countries, and perhaps worldwide.