FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3037957894> ?p ?o ?g. }

• W3037957894 abstract "Abstract Background Fundus images allow for non-invasive assessment of the retinal vasculature whose features provide important information on health. Blood vessel tortuosity is a morphological feature associated with many diseases including hypertension. Methods We analyzed 116 639 fundus images of suitable quality from 63 662 participants from three cohorts, namely the UK Biobank (n = 62 751), SKIPOGH (n = 397), and OphtalmoLaus (n = 512). We used a fully automated image processing pipeline to annotate vessels and a deep learning algorithm to determine the vessel type, characterizing these subjects in terms of their median retinal vessel tortuosity specific to arteries and to veins. Tortuosity was measured by the distance factor (the length of a vessel segment over its chord length), as well as measures that integrate over vessel curvature. Using these measures as traits, we performed the largest genome-wide association study (GWAS) of vessel tortuosity to date. We assessed gene set enrichment using the novel high-precision statistical method PascalX . Results Higher tortuosity was significantly associated with higher incidence of angina, myocardial infarction, stroke, deep vein thrombosis, and hypertension. We identified 175 significantly associated genetic loci in the UK Biobank; 173 of these were novel and 4 replicated in our second, much smaller, meta-cohort. We estimated heritability at ∼25% using linkage disequilibrium score regression. Vessel type specific GWAS revealed 114 loci for arteries and 63 for veins. Genes with significant association signals included COL4A2, ACTN4, LGALS4, LGALS7, LGALS7B, TNS1, MAP4K1, EIF3K, CAPN12, ECH1, and SYNPO2. These tortuosity genes were overexpressed in arteries and heart muscle and linked to pathways related to the structural properties of the vasculature. We demonstrated that tortuosity loci served pleiotropic functions as cardiometabolic disease variants and risk factors. Concordantly, Mendelian randomization revealed causal effects between tortuosity, BMI and LDL. Conclusions Several alleles associated with retinal vessel tortuosity point to a common genetic architecture of this trait with cardiovascular diseases and metabolic syndrome. Our results shed new light on the genetics of vascular diseases and their pathomechanisms and highlight how GWASs and heritability can be used to improve phenotype extraction from high-dimensional data, such as images. Clinical Perspective What is new? We automatically estimated arterial and venous tortuosity in over 100k retinal fundus images using image analysis and deep learning. GWAS revealed 173 novel loci. Mendelian randomization showed that increased venous tortuosity reduces BMI whereas elevated LDL levels reduce the tortuosity of both arteries and veins. Measuring tortuosity in terms of the distance factor , which is sensitive to total vessel elongation, had higher heritability and more associated loci than other tortuosity measures that are sensitive to local vessel bending. What are the clinical implications? Tortuosity genes were overexpressed in the aorta, tibial artery, coronary artery, and in two heart tissues. Higher tortuosity was associated with higher incidence of angina, myocardial infarction, stroke, deep vein thrombosis and hypertension. We demonstrated a shared genetic architecture between retinal tortuosity and certain diseases related to the vasculature, and the associations included several cardiometabolic disease variants and risk factors. Further research is needed to investigate the potential of the retinal vessel tortuosity as a clinically relevant biomarker for cardiovascular disease and metabolic syndrome. Enriched pathways include a well-known therapeutic target for ocular diseases (VEGFA-VEGFR2) affecting tissue remodeling. We highlight several transcription factors as interesting targets for further experimentation." @default.
• W3037957894 created "2020-07-02" @default.
• W3037957894 creator A5005763014 @default.
• W3037957894 creator A5052282478 @default.
• W3037957894 creator A5059267796 @default.
• W3037957894 creator A5060278610 @default.
• W3037957894 creator A5061196788 @default.
• W3037957894 creator A5062662732 @default.
• W3037957894 creator A5072307317 @default.
• W3037957894 date "2020-06-26" @default.
• W3037957894 modified "2023-10-11" @default.
• W3037957894 title "Genome-Wide Association Studies of retinal vessel tortuosity identify 173 novel loci, capturing genes and pathways associated with disease and vascular tissue pathomechanics" @default.
• W3037957894 cites W1543225485 @default.
• W3037957894 cites W1787824584 @default.
• W3037957894 cites W1905058580 @default.
• W3037957894 cites W1968421760 @default.
• W3037957894 cites W1970072800 @default.
• W3037957894 cites W1970360178 @default.
• W3037957894 cites W1980795503 @default.
• W3037957894 cites W1989881480 @default.
• W3037957894 cites W1990824174 @default.
• W3037957894 cites W1992911777 @default.
• W3037957894 cites W1993427098 @default.
• W3037957894 cites W1995904975 @default.
• W3037957894 cites W2001629081 @default.
• W3037957894 cites W2001885074 @default.
• W3037957894 cites W2006039944 @default.
• W3037957894 cites W2006670749 @default.
• W3037957894 cites W2010457001 @default.
• W3037957894 cites W2011540186 @default.
• W3037957894 cites W2016317262 @default.
• W3037957894 cites W2018838463 @default.
• W3037957894 cites W2019778763 @default.
• W3037957894 cites W2024108088 @default.
• W3037957894 cites W2025086473 @default.
• W3037957894 cites W2025973019 @default.
• W3037957894 cites W2030756257 @default.
• W3037957894 cites W2034530918 @default.
• W3037957894 cites W2038683364 @default.
• W3037957894 cites W2054153086 @default.
• W3037957894 cites W2057673193 @default.
• W3037957894 cites W2059088148 @default.
• W3037957894 cites W2062615129 @default.
• W3037957894 cites W2065119658 @default.
• W3037957894 cites W2065195353 @default.
• W3037957894 cites W2066218332 @default.
• W3037957894 cites W2073062251 @default.
• W3037957894 cites W2078239496 @default.
• W3037957894 cites W2082206872 @default.
• W3037957894 cites W2082599944 @default.
• W3037957894 cites W2082704080 @default.
• W3037957894 cites W2086084700 @default.
• W3037957894 cites W2092074451 @default.
• W3037957894 cites W2095821741 @default.
• W3037957894 cites W2096333975 @default.
• W3037957894 cites W2097005219 @default.
• W3037957894 cites W2101301751 @default.
• W3037957894 cites W2102622802 @default.
• W3037957894 cites W2104801393 @default.
• W3037957894 cites W2106036991 @default.
• W3037957894 cites W2106523452 @default.
• W3037957894 cites W2112409097 @default.
• W3037957894 cites W2112848098 @default.
• W3037957894 cites W2115779804 @default.
• W3037957894 cites W2122639624 @default.
• W3037957894 cites W2128006311 @default.
• W3037957894 cites W2128736149 @default.
• W3037957894 cites W2129254992 @default.
• W3037957894 cites W2130410032 @default.
• W3037957894 cites W2132846716 @default.
• W3037957894 cites W2136662125 @default.
• W3037957894 cites W2143079975 @default.
• W3037957894 cites W2146980885 @default.
• W3037957894 cites W2149200222 @default.
• W3037957894 cites W2155658028 @default.
• W3037957894 cites W2156564520 @default.
• W3037957894 cites W2163705275 @default.
• W3037957894 cites W2164239451 @default.
• W3037957894 cites W2168836911 @default.
• W3037957894 cites W2170789385 @default.
• W3037957894 cites W2171367439 @default.
• W3037957894 cites W2191829633 @default.
• W3037957894 cites W2199106471 @default.
• W3037957894 cites W2216458865 @default.
• W3037957894 cites W2254879037 @default.
• W3037957894 cites W2288526945 @default.
• W3037957894 cites W2318236171 @default.
• W3037957894 cites W2345621280 @default.
• W3037957894 cites W2416911783 @default.
• W3037957894 cites W2521974668 @default.
• W3037957894 cites W2526666881 @default.
• W3037957894 cites W2547569497 @default.
• W3037957894 cites W2557738935 @default.
• W3037957894 cites W2568435545 @default.
• W3037957894 cites W2581452190 @default.
• W3037957894 cites W2604218568 @default.
• W3037957894 cites W2609543937 @default.
• W3037957894 cites W2618738897 @default.
• W3037957894 cites W2626947344 @default.
• W3037957894 cites W2702621018 @default.

• next