Novel functional insights into ischemic stroke biology provided by the first genome-wide association study of stroke in indigenous Africans

\ua9 The Author(s) 2024. Background: African ancestry populations have the highest burden of stroke worldwide, yet the genetic basis of stroke in these populations is obscure. The Stroke Investigative Research and Educational Network (SIREN) is a multicenter study involving 16 sites in West Africa. We conducted the first-ever genome-wide association study (GWAS) of stroke in indigenous Africans. Methods: Cases were consecutively recruited consenting adults (aged > 18 years) with neuroimaging-confirmed ischemic stroke. Stroke-free controls were ascertained using a locally validated Questionnaire for Verifying Stroke-Free Status. DNA genotyping with the H3Africa array was performed, and following initial quality control, GWAS datasets were imputed into the NIH Trans-Omics for Precision Medicine (TOPMed) release2 from BioData Catalyst. Furthermore, we performed fine-mapping, trans-ethnic meta-analysis, and in silico functional characterization to identify likely causal variants with a functional interpretation. Results: We observed genome-wide significant (P-value < 5.0E−8) SNPs associations near AADACL2 and miRNA (MIR5186) genes in chromosome 3 after adjusting for hypertension, diabetes, dyslipidemia, and cardiac status in the base model as covariates. SNPs near the miRNA (MIR4458) gene in chromosome 5 were also associated with stroke (P-value < 1.0E−6). The putative genes near AADACL2, MIR5186, and MIR4458 genes were protective and novel. SNPs associations with stroke in chromosome 2 were more than 77 kb from the closest gene LINC01854 and SNPs in chromosome 7 were more than 116 kb to the closest gene LINC01446 (P-value < 1.0E−6). In addition, we observed SNPs in genes STXBP5-AS1 (chromosome 6), GALTN9 (chromosome 12), FANCA (chromosome 16), and DLGAP1 (chromosome 18) (P-value < 1.0E−6). Both genomic regions near genes AADACL2 and MIR4458 remained significant following fine mapping. Conclusions: Our findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke’s risk prediction and development of new targeted interventions to prevent or treat stroke

Linseed essential oil - source of lipids as active ingredients for pharmaceuticals and nutraceuticals

Linseed - also known as flaxseed - is known for its beneficial effects on animal health attributed to its composition. Linseed comprises linoleic and ?-linolenic fatty acids, various dietary fibers and lignans, which are beneficial to health because they reduce the risk of cardiovascular diseases, as well as cancer, decreasing the levels of cholesterol and relaxing the smooth muscle cells in arteries increasing the blood flow. Essential fatty acids from flax participate in several metabolic processes of the cell, not only as structuring components of the cell membrane but also as storage lipids. Flax, being considered a functional food, can be consumed in a variety of ways, including seeds, oil or flour, contributing to basic nutrition. Several formulations containing flax are available on the market in the form of e.g. capsules and microencapsulated powders having potential as nutraceuticals. This paper revises the different lipid classes found in flaxseeds and their genomics. It also discusses the beneficial effects of flax and flaxseed oil and their biological advantages as ingredients in pharmaceuticals and in nutraceuticals products.The authors wish to acknowledge the financial support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020 for the project M-ERA-NET/0004/2015-PAIRED.info:eu-repo/semantics/publishedVersio