| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Investigative Opthalmology & Visual Science | ||||
| Publisher: | ASSOC RESEARCH VISION OPHTHALMOLOGY INC | ||||
| Place of Publication: | ROCKVILLE | ||||
| Volume: | 60 | ||||
| Number of Issue or Book Chapter: | 12 | ||||
| Page Range: | p. 4041 | ||||
| Date: | 2019 | ||||
| Institutions: | Medicine > Lehrstuhl für Augenheilkunde Medicine > Lehrstuhl für Humangenetik Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie | ||||
| Identification Number: |
| ||||
| Keywords: | GROWTH-FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; CELL-SURVIVAL; ACTIVATION; ASSOCIATION; VARIANTS; NETWORKS; THERAPY; RARE; age-related macular degeneration; pathway analysis; genome-wide association study; database; phospholipase C gamma 2 | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 48276 |
Web of ScienceAbstract
PURPOSE. Age-related macular degeneration (AMD) is the worldwide leading cause of blindness among the elderly. Although genome-wide association studies (GWAS) have identified AMD risk variants, their roles in disease etiology are not well-characterized, and they only explain a portion of AMD heritability. METHODS. We performed pathway analyses using summary statistics from the International AMD ...
Abstract
PURPOSE. Age-related macular degeneration (AMD) is the worldwide leading cause of blindness among the elderly. Although genome-wide association studies (GWAS) have identified AMD risk variants, their roles in disease etiology are not well-characterized, and they only explain a portion of AMD heritability. METHODS. We performed pathway analyses using summary statistics from the International AMD Genomics Consortium's 2016 GWAS and multiple pathway databases to identify biological pathways wherein genetic association signals for AMD may be aggregating. We determined which genes contributed most to significant pathway signals across the databases. We characterized these genes by constructing protein-protein interaction networks and performing motif analysis. RESULTS. We determined that eight genes (C2, C3, LIPC, MICA, NOTCH4, PLCG2, PPARA, and RAD51B) "drive'' the statistical signals observed across pathways curated in the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Ontology (GO) databases. We further refined our definition of statistical driver gene to identify PLCG2 as a candidate gene for AMD due to its significant gene-level signals (P < 0.0001) across KEGG, Reactome, GO, and NetPath pathways. CONCLUSIONS. We performed pathway analyses on the largest available collection of advanced AMD cases and controls in the world. Eight genes strongly contributed to significant pathways from the three larger databases, and one gene (PLCG2) was central to significant pathways from all four databases. This is, to our knowledge, the first study to identify PLCG2 as a candidate gene for AMD based solely on genetic burden. Our findings reinforce the utility of integrating in silico genetic and biological pathway data to investigate the genetic architecture of AMD.
Metadata last modified: 03 Sep 2021 09:47
Altmetric