Principal Investigator: Professor Joel Gelernter
Department: School of Medicine
Yale University, School of Medicine, Psychiatry, Genetics and Neurobiology, VA CT 116A2, 950 Campbell Avenue, West Haven CT 06516. United StatesTags: 19664 Phenome-wide; Polygenic; Genetic_Correlation; Complex Traits
1a: Genome-Wide Association Studies (GWAS) have demonstrated that the genetic predisposition to complex traits is highly polygenic (i.e., many variants with small effects). Polygenic Risk Score (PRS) analysis uses the GWAS results to investigate both genetic correlations among complex phenotypes and the genetics of traits not previously analyzed. Phenome-wide Association Studies (PheWAS) are a novel approach utilized to extend systematically the phenotype associations of known genetic loci. Applying the PheWAS approach to PRS of several complex traits, we will investigate the genetic correlations among complex traits, also expanding our knowledge related to the genetics of uninvestigated phenotypes.
1b: The results expected from the current proposal will generate novel data regarding the mechanisms at the basis of complex traits (i.e., risk loci, molecular pathways involved, tissue/cell-type enrichments, and genetic overlapping among different traits). This information will surely help to improve the prevention, diagnosis, and treatment of a wide range of serious and life-threatening illnesses. For this reason, we think that our project is perfectly in line with the main UK Biobank’s purpose.
1c: Heritability studies demonstrated that common traits have a consistent genetic component: single genes cannot account for the genetic part of the predisposition to common traits, but this is due to numerous genes each with small effects. Large genetic studies conducted by international scientific consortia generated a huge amount of data that we can use to investigate the genetic predisposition of pathologic and physiologic phenotypes. In the current proposal, we will apply these data to analyze systematically the genetics of a wide range of traits, providing novel findings about their predisposition and the potential overlapping mechanisms at their basis.
1d: We require the full UK Biobank cohort subjects with complete phenotype and genotype information (data collected at the Assessment Centre and imputed genotypes, respectively).