Craig Smail, PhD
Assistant Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Assistant Professor of Pediatrics, University of Kansas School of Medicine
Full BiographyCraig Smail, PhD, of the Genomic Medicine Center, was recently awarded a two-year, $429,000 R21 Novel Approaches for Relating Genetic Variation to Function and Disease grant from the National Human Genome Research Institute of the National Institutes of Health under award number R21HG012422.
Dr. Smail’s study, “Novel computational approaches to characterize the effects of rare functional outlier variants on cis- and trans-regulatory disease processes,” will work to understand the genome-wide impact of rare genetic variants on personalized complex disease risk.
As Dr. Smail explains, rare genetic variants are abundant in the human genome and can have large effects on individual risk for complex disease. However, these variants are difficult to interpret and new approaches are required to provide genome-wide resolution of rare variant effects.
He and his team will develop and apply novel computational methods integrating functional genomic and biobank-scale phenotypic resources to provide the first systematic characterization of personalized complex disease risk contributed by rare genetic variants. Because rare variants can have very large effects on molecular phenotypes (such as gene expression) and downstream disease risk, they provide a powerful system to understand genetic regulation of nearby genes (so-called cis-regulation) as well as long-range gene regulation affecting genes located distally from a rare variant, even on different chromosomes (trans-regulation). These two systems of regulation are almost impossible to comprehensively characterize using traditional methods such as genome wide association studies (GWAS) due to limited statistical power.
“Overall, these activities will increase our understanding of the biology of complex disease and advance the implementation of personalized genomic medicine,” said Dr. Smail. “Our efforts will provide important contributions to understanding the rapidly growing discovery of rare variants from whole genome data and the urgent need for methods to interpret these variants.”
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