Diverse ancestry GWAS for advanced age-related macular degeneration in TOPMed-imputed and Ophthalmologically-confirmed 16,108 cases and 18,038 controls
Gorski, M.; Grunin, M.; Herold, J. M.; Froehlich, B.; Behr, M.; Wheeler, N.; Bush, W. S.; Song, Y. E.; Zhu, X.; Blanton, S. H.; Pericak-Vance, M. A.; Heid, I. M.; Haines, J. L.
Show abstract
Age-related macular degeneration (AMD) is a leading cause of blindness with $344 billion dollars global costs. In 2016, the International Age-related Macular Degeneration Genomics Consortium devised genomic data on [~]50,000 individuals (IAMDGC 1.0) and identified 52 variants across 34 loci associated with advanced AMD in European ancestry. We have now analyzed a more densely imputed version (IAMDGC 2.0) and performed cross-ancestry GWAS in 16,108 advanced AMD cases and 18,038 AMD-free controls. This identified 28 loci at P<5x10-8, including two additional AMD loci compared to IAMDGC 1.0 (SERPINA1 and CPN1). Fine-mapping supported one ancestry-shared signal around HTRA1/ARMS2 and nine signals around CFH without African ancestry contribution. The 52-variant genetic risk score with and the 44-variant score without CFH-variants predicted advanced AMD not only in EUR, but also in AFR and ASN (AUC=0.80/0.75, 0.65/0.64, 0.80/0.79, respectively). Our results indicate that the genetic underpinning of advanced AMD is mostly shared between ancestries.
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