Ischemic Stroke: From Next Generation Sequencing and GWAS to Community Genomics?

Abstract

Stroke is a major cause of mortality and morbidity in both the developed and developing world. Next generation sequencing (NGS) and multi-omics integrative biology research offer new opportunities in the way we research and understand stroke. These biotechnologies also signal a shift from genetics to genomics of stroke, which is highlighted in this review. Stroke is a focal neurological deficit resulting from disruption of the cerebral blood supply. There are two main types of common stroke, ischemic stroke (IS), which comprises 80% of cases, and hemorrhagic stroke (HS) that accounts for about 20% of cases. IS is a complex multi-factorial disease with multiple environmental and genomic determinants. We discuss here IS from genomics and bioinformatics perspectives, including the highlights of the genome wide association studies (GWAS), NGS progress to date, and exome studies. While both \u27common variant, common disease\u27 and \u27rare variant, common disease\u27 approaches need to be assessed in tandem, future studies into IS omics should also consider pedigree and/or community based sampling to take account of the complex diversity of IS genetics. We conclude by presenting an example of such community genomics research from China in an extended pedigree sample, and the ways in which the intersection of genomics and global society can usefully inform our understanding of IS pathophysiology and potential preventive medicine interventions in the future

Ischemia/Reperfusion

“…Genome-wide association studies have been used to examine myocardial gene expression signatures, identifying approximately 152 genomic loci and over 300 genes that may contribute to enhanced risk for coronary artery disease and myocardial infarction (52, 74, 75, 112, 597, 765, 855). This genomic analysis has also uncovered chromosomal locations associated with ischemic stroke and peripheral artery disease, with some loci in common to those associated with coronary disease and heart attack.…”

Vasoregression: A Shared Vascular Pathology Underlying Macrovascular And Microvascular Pathologies?

“…V ascular research has been at the epicenter of integrative biology scholarship (Black and Wang, 2015). The part of the cardiovascular system that transports oxygenated blood away from the heart through the aorta of the left ventricle, and delivers it to the body tissues is termed as systemic circulation.…”

Genetics of Sickle Cell-Associated Cardiovascular Disease: An Expert Review with Lessons Learned in Africa

“…This substantiates the need for research focusing on the association between gene polymorphisms and disease phenotypes to facilitate better prediction of the clinical course of SCD in sub-Saharan Africa, the region with the highest burden of disease. More advanced techniques such as genomewide association studies (GWAS), whole-exome sequencing (WES), and whole-genome sequencing (WGS) represent a shift from genetics to genomics (Black et al, 2015), which is also required to identify novel loci that may contribute to the predisposition to complex and multifactorial disease-related cardiovascular phenotypes.…”

“…These techniques also require extensive bioinformatic resources and support, which in addition to long-term financial support, the availability of adequately trained personnel, and the regulation and structure of healthcare frameworks, prove to be potential barriers to the development of genomic medical centers in low-and middleincome countries (Black et al, 2015;Forero et al, 2016).…”