Myriam Fornage, PhD
Professor, McGovern Medical School Institute of Molecular Medicine Research Center for Human Genetics
Recent News
Grand challenges in stroke genomics
Stroke, a leading cause of death, disability and dementia, is a significant public health burden with enormous financial and human costs that are projected to rise over the next decades due to demographic shifts in populations around the globe (Donkor, 2018). Stroke is a complex and heterogeneous disease encompassing multiple etiological subtypes. Recent genetics and omics studies have yielded some exciting novel insights into stroke pathophysiology and the promise of new advances in stroke prevention, diagnosis, treatment, and outcome. In particular, genome-wide association studies (GWAS) have proven an essential tool to identify common variants associated with stroke, thus unveiling previously unsuspected biological mechanisms underlying stroke and stroke subtypes .
Cerebral small vessel disease genomics and its implications across the lifespan
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
Association of blood pressure with cognitive function at midlife: a Mendelian randomization study
Whether high blood pressure has a causal effect on cognitive function as early as middle age is unclear. We investigated whether high blood pressure (BP) causally impairs cognitive function at midlife using Mendelian Randomization (MR).
Genome-Wide Association Study Meta-Analysis of Stroke in 22,000 Individuals of African Descent Identifies Novel Associations With Stroke
Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans.
Dr. Fornage's research interests lie in the molecular genetics of complex diseases, with an emphasis on cerebrovascular disease and stroke.
Dr. Fornage received her Ph.D. from the University of Texas - Houston in 1996. She pursued her post-doctoral training in the Department of Genetics at Case Western University, Cleveland, Ohio. She joined the Institute of Molecular Medicine, University of Texas - Houston, in 1998 as a Research Fellow, was appointed Assistant Professor of Molecular Medicine in 2000, and Associate Professor in 2007. Dr. Fornage is also a faculty member of the Graduate School of Biomedical Sciences Program in Human and Molecular Genetics. Her research interests lie in the molecular genetics of complex diseases, with an emphasis on cerebrovascular disease and stroke. She is a member of the American Society of Human Genetics and the American Heart Association Stroke Council.
Current research is directed at understanding the genetic basis of brain vascular injury using functional genomic and genetic epidemiology strategies. Work in Dr. Fornage's laboratory employs microarray gene expression profiling and 2D gel electrophoresis proteomic analysis to identify genes and gene pathways contributing to stroke susceptibility in the stroke-prone spontaneously hypertensive rat (SHRSP). These studies recently identified the gene encoding soluble epoxide hydrolase, an enzyme involved in endothelium function, cerebral functional hyperemia, and angiogenesis, as a candidate gene influencing susceptibility to brain vascular injury in this model. Ongoing work is aimed at identifying the set of genes that comprises the molecular network underlying soluble epoxide hydrolase function in vascular disease.
Discovery of the molecular mechanisms contributing to increased susceptibility to brain lesions in the SHRSP provides the basis for investigation of these pathogenetic mechanisms in the development of human cardiovascular disease. Therefore, Dr. Fornage's laboratory also investigates whether variation in the human orthologues of the genes identified in the rat model influences risk of developing cardiovascular disease in the human population. She recently reported that sequence variation in the human soluble epoxide hydrolase gene influences risk for ischemic stroke in African-Americans and European-Americans.
Dr. Fornage is an investigator of the NHLBI Coronary Artery Disease Risk Development in Young Adults (CARDIA) study, a multi-center study of the distribution and evolution of coronary heart disease risk factors from young adulthood to middle-age. Her contribution to the study is directed toward the investigation of the interaction between genes and environmental factors that contribute to the development of coronary heart disease in young adults. Ongoing work investigates the interactions of variation in genes involved in eicosanoid synthesis and metabolism with dietary intake of fatty acids on the development and progression of atherosclerosis and its risk factors.