In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 19, No. 8 ( 2023-8-16), p. e1010609-
Abstract:
Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p 〈 5x10 -8 ). The strongest association was rs2239785, (K150E) in APOL1 . The second finding was rs10402468, which co-localized to PLVAP and ANKLE1 in vascular / endothelium tissues. We conducted multiple sensitivity analyses to establish that the associations were specific to DME status and did not reflect diabetes status or other diabetic complications. Here we report two novel loci for risk of DME which replicated in multiple clinical trial and biobank derived datasets. One of these loci, containing the gene APOL1 , is a risk factor in African American DME and DKD patients, indicating that this locus plays a broader role in diabetic complications for multiple ancestries. Trial Registration: NCT00473330 , NCT00473382 , NCT03622580 , NCT03622593 , NCT04108156 .
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010609
DOI:
10.1371/journal.pgen.1010609.g001
DOI:
10.1371/journal.pgen.1010609.g002
DOI:
10.1371/journal.pgen.1010609.g003
DOI:
10.1371/journal.pgen.1010609.g004
DOI:
10.1371/journal.pgen.1010609.t001
DOI:
10.1371/journal.pgen.1010609.t002
DOI:
10.1371/journal.pgen.1010609.t003
DOI:
10.1371/journal.pgen.1010609.t004
DOI:
10.1371/journal.pgen.1010609.s001
DOI:
10.1371/journal.pgen.1010609.s002
DOI:
10.1371/journal.pgen.1010609.s003
DOI:
10.1371/journal.pgen.1010609.s004
DOI:
10.1371/journal.pgen.1010609.s005
DOI:
10.1371/journal.pgen.1010609.s006
DOI:
10.1371/journal.pgen.1010609.s007
DOI:
10.1371/journal.pgen.1010609.s008
DOI:
10.1371/journal.pgen.1010609.s009
DOI:
10.1371/journal.pgen.1010609.s010
DOI:
10.1371/journal.pgen.1010609.s011
DOI:
10.1371/journal.pgen.1010609.s012
DOI:
10.1371/journal.pgen.1010609.s013
DOI:
10.1371/journal.pgen.1010609.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2186725-2
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