Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema
Stockwell, A. D.; Chang, M.; Mahajan, A.; Forrest, W.; Anegondi, N.; Pendergrass, R.; Selvaraj, S.; Reeder, J.; Wei, E.; Iglesias, V.; Creps, N.; Macri, L.; Neeranjan, A.; van der Brug, M.; Scales, S.; McCarthy, M.; Yaspan, B. L.
Show 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.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21 93%
- Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity 91%
- Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and senile systemic amyloidoses 91%
Similar papers in this journal
- Interpreting coronary artery disease GWAS results: A functional genomics approach assessing biological significance 94%
- Genetically regulated gene expression underlies lipid traits in Hispanic cohorts 93%
- A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in the LPA promoter 93%
Similar papers in this journal
- GWAS in Africans identifies novel lipids loci and demonstrates heterogenous association within Africa 95%
- Heritability and family-based GWAS analyses of the N-acyl ethanolamine and ceramide plasma lipidome 95%
- The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: A Mendelian randomization study 95%
Similar papers in this journal
- Analysis of Genetically Determined Gene Expression Suggests Role of Inflammatory Processes in Exfoliation Syndrome 93%
- Common variation in a long non-coding RNA gene modulates variation of circulating TGF- β 2 levels in metastatic colorectal cancer patients (Alliance) 92%
- Similarity and diversity of genetic architecture for complex traits between East Asian and European populations 92%
Similar papers in this journal
- Genome-Wide Association Meta-Analysis Using a Recessive Model Illuminates Genetic Architecture of Type 2 Diabetes 97%
- Plasma proteomic signatures of adiposity are associated with cardiovascular risk factors and type 2 diabetes risk in a multi-ethnic Asian population 93%
- Characterizing common and rare variations in non-traditional glycemic biomarkers using multivariate approaches on multi-ancestry ARIC study 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.