Genes Associated with Age-Related Macular Degeneration Identified

Age-Related Macular Degeneration (AMD) is a complex disease influenced by yet-to-be-understood mix of genetic and behavioral factors. Smoking increases the risk of developing the disease, while eating leafy greens and fish reduces it.

Previously, scientists have compared populations of people with and without AMD and identified 34 small genomic regions, called loci, and 52 genetic variants within these loci that were significantly associated with AMD.


A team of scientists from different institutions working with the US National Eye Institute (Bethesda, MD, USA) studied 453 retinas, the eye tissue affected by AMD, from deceased human donors with and without AMD. The analysis involved sequencing each retina's ribonucleic acid (RNA), the messenger molecule that carries instructions from DNA for making proteins. A total of 13,662 protein-coding and 1,462 non-protein coding RNA sequences were identified.

To search for the genetic variants regulating gene expression in the retina, they used expression quantitative trait loci (eQTL) analysis. Computational methods allowed the team to detect patterns between the genes expressed in the retina and a pool of more than nine million previously identified genetic variants. Specifically, they looked for variants with a high probability of being responsible for variations in gene expression among people with and without AMD. The analysis pointed to target disease genes at six of the 34 AMD loci identified in the earlier studies.

Among the most plausible target genes were B3GLCT and BLOC1S1, which could affect AMD-related cell functions such as signaling; the breakdown and disposal of unwanted proteins; and the stability of the extracellular matrix, the cell's infrastructure for distribution. The scientists used transcriptome-wide association analysis (TWAS) they identified three additional genes, RLBP1, HIC1 and PARP12. The analysis also suggested as many as 20 additional candidate genes providing insights into the genes and pathways involved in pathobiology of AMD.

Rinki Ratnapriya, PhD, the first author of the study, said, “So far, most studies in AMD have focused on analyses of genetic variants in DNA. This study for the first time leverages transcriptional (RNA) data to expand on the genetic architecture of AMD.” The study was published on February 11, 2019, in the journal Nature Genetics.

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US National Eye Institute