To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts ( = 3,246) and seven African American cohorts ( = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a value <1 × 10 were investigated in replication cohorts that included 18,545 European, 16,453 Asian, and 2,710 Hispanic subjects. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like ( ) was associated with DR in European discovery cohorts ( = 2.1 × 10 ), but did not reach genome-wide significance after meta-analysis with replication cohorts. We applied the Disease Association Protein-Protein Link Evaluator (DAPPLE) to our discovery results to test for evidence of risk being spread across underlying molecular pathways. One protein-protein interaction network built from genes in regions associated with proliferative DR was found to have significant connectivity ( = 0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in as well as variation within a protein-protein interaction network that includes genes implicated in inflammation, may influence risk for DR.
Reference Type
Journal Article
Periodical Full
Diabetes (New York, N.Y.)
Publication Year
2019
Publication Date
Feb
Volume
68
Issue
2
Start Page
441
Other Pages
456
Publisher
American Diabetes Association
Place of Publication
United States
ISSN/ISBN
0012-1797
Document Object Index
10.2337/db18-0567
URL
https://www.ncbi.nlm.nih.gov/pubmed/30487263 https://www.ncbi.nlm.nih.gov/pubmed/30487263