ArticleHuman genetics2016
Exome-based case-control association study using extreme phenotype design reveals novel candidates with protective effect in diabetic retinopathy.
Article in Human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 4 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 4 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Pooled it
- Gene Set Enrichment Analsyes Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy.American journal of ophthalmology · 2022Pooled it
- Pooled it
- Pooled it
- Circulating microRNAs as diagnostic biomarkers and pathogenic mediators in type 2 diabetic retinopathy: a systematic review.Acta diabetologica · 2026Review
- Whole-Exome Analysis Identifies Candidate Genes Associated With Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026Article
- Exome and Genome Sequencing Reveals Novel Variants for Severe Diabetic Retinopathy in Type 1 Diabetes.Investigative ophthalmology & visual science · 2025Article
- New insights of potential biomarkers in diabetic retinopathy: integrated multi-omic analyses.Frontiers in endocrinology · 2025Review
- Adaptive selection at G6PD and disparities in diabetes complications.Nature medicine · 2024Article
- Genetic insights and emerging therapeutics in diabetic retinopathy: from molecular pathways to personalized medicine.Frontiers in genetics · 2024Review
- Identification of Genetic Variants for Diabetic Retinopathy Risk Applying Exome Sequencing in Extreme Phenotypes.BioMed research international · 2024Article
- Genomic profile of diabetic retinopathy in a north indian cohort.Molecular biology reports · 2023Article
- Genetics of diabetes-associated microvascular complications.Diabetologia · 2023Review
- Whole-exome sequencing study identifies four novel gene loci associated with diabetic kidney disease.Human molecular genetics · 2023Article
- A Guide to Genome-Wide Association Study Design for Diabetic Retinopathy.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Heterogeneity in biomarkers, mitogenome and genetic disorders of the Arab population with special emphasis on large-scale whole-exome sequencing.Archives of medical science : AMS · 2023Article
- Genome-wide DNA methylation analysis of extreme phenotypes in the identification of novel epigenetic modifications in diabetic retinopathy.Clinical epigenetics · 2022Article
- Identifying gene variants underlying the pathogenesis of diabetic retinopathy based on integrated genomic and transcriptomic analysis of clinical extreme phenotypes.Frontiers in genetics · 2022Article
- Contribution of Rare and Low-Frequency Variants to Multiple Sclerosis Susceptibility in the Italian Continental Population.Frontiers in genetics · 2021Article
- Genetics of diabetes mellitus and diabetes complications.Nature reviews. Nephrology · 2020Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledDiabetic retinopathy (DR) is a common clinical expression of diabetes mellitus-induced vasculopathy and is a major cause of vision loss. Significant gaps remain in our understanding of the molecular pathoetiology of DR, and it is hoped that human genetic approaches can reveal novel targets especially since DR is a heritable trait. Previous studies have focused on genetic risk factors of DR but their results have been mixed. In this study, we hypothesized that the use of the extreme phenotype design will increase the power of a genomewide search for "protective" genetic variants. We enrolled a small yet atypical cohort of 43 diabetics who did not develop DR a decade or more after diagnosis (cases), and 64 diabetics with DR (controls), all of similar ethnic background (Saudi). Whole-exome sequencing of the entire cohort was followed by statistical analysis employing combined multivariate and collapsing methods at the gene level, to identify genes that are enriched for rare variants in cases vs. CONTROLS: Three genes (NME3, LOC728699, and FASTK) reached gene-based genome-wide significance at the 10(-08) threshold (p value = 1.55 × 10(-10), 6.23 × 10(-10), 3.21 × 10(-08), respectively). Our results reveal novel candidate genes whose increased rare variant burden appears to protect against DR, thus highlighting them as attractive candidate targets, if replicated by future studies, for the treatment and prevention of DR. Extreme phenotype design when implemented in sequencing-based genome-wide case-control studies has the potential to reveal novel candidates with a smaller cohort size compared to standard study designs.
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