Abstract
Purpose :
Nutrient-based interventions are used for tertiary prevention of advanced AMD. Pleiotropic loci exist for AMD and health conditions characterized by altered nutrient absorption.
Methods :
We examined advanced AMD (AAMD)-associated missense DNA variants from the IAMDC|GWAS Catalog|PheWeb for pleiotropy with Celiac Disease (CD), a condition characterized by malabsorption of zinc (a key constituent of the AREDS formulation) and other minerals linked to diet-associated reductions in likelihood of having or progressing to AAMD. The genetic architecture of co-inherited SNPs in people of western-European ancestry (r2 > 0.80, LDLink-NCI and HaploReg 4.1) was also analyzed.
Results :
Analysis of IAMDC, GWAS Catalog and PheWeb data showed that 13 genes containing AAMD-related (P < 1.0E-7) exonic SNPs also carry CD-associated DNA variants. Analysis of all concordant genes (those containing any form of genome-wide AAMD- and CD-related variation) yielded a CD enrichment Q-value of 2.3E-18. We filtered IAMDC results for AAMD by genome-wide CD-associated loci (P < 1.0E-7) that were identified in a fine-mapping study on > 24,000 people (PMID: 22057235). Within the 6p21 locus, 58 SNPs in 25 LD-independent (r2 < 0.60) loci were both associated with AAMD and CD. These loci include SNPs in complete LD (r2 > 1.0) with 6 missense DNA sequence variants (in CCHCR1, MSH5, C2, CFB, TNXB, PSMB9).
Conclusions :
Our findings provide a reasonable basis for investigating the possibility of a common underlying biology and therapeutic options for AAMD and Celiac Disease through processes driven by proteins encoded by genes in the 6p21 locus.
This is a 2021 ARVO Annual Meeting abstract.