Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.

There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P < 1e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.

Comparative Transcriptome Profile between Iberian Pig Varieties Provides New Insights into Their Distinct Fat Deposition and Fatty Acids Content.

The high deposition of intramuscular fat and the content of oleic fatty acid are characteristic of the Iberian pig. These two parameters present great variability and are differentiated amongst the varieties that make up the Iberian pig population. Although previous studies generated evidence for causal genes and polymorphisms associated to the adipogenic potential of the Iberian pig, there is little information about how genetic expression influences this trait's variability. The aim of this study was to analyses the expression profile between two varieties of Iberian pig (Torbiscal and Retinto) and their reciprocal crosses differentiated in their intramuscular fat (IMF) content and fatty acid (FA) composition in the Longissimus thoracis muscle using an RNA-seq approach. Our results corroborate that the Retinto variety is the fattiest amongst all studied varieties as its upregulated genes, such as FABP3 and FABP5, SLC27A1 and VEGFA among others, contribute to increasing adiposity. In its turn, Torbiscal pigs showed an upregulation of genes associated with the inhibition of fat deposition such as ADIPOQ and CPT1A. Further genetic variation analysis in these Iberian varieties showed relevant associations for SNP located within the differentially expressed genes with IMF and FA content. Thus, the differences found in the genetic architecture and the muscle transcriptome of these Iberian varieties might explain the variability in their fat content and composition and hence, their meat quality.