A new reference panel to boost African American genotype imputation

Project Summary Modern genetic studies have been conducted predominantly in cohorts of individuals of European ancestry By there were approximately ten times as many published genome wide association studies GWAS in people of European ancestry than studies in people of all other ancestries combined This research disparity has led to an uneven understanding of the genetic basis underlying disease in Europeans and non Europeans andMeandapos s web based large scale research model is ideal for scaling genetics research within non European populations and thereby bringing more parity to genetics research Our database is composed of genotypes and phenotypes of over consenting customers including over individuals with non European ancestry The data derived from non European individuals represent a particularly valuable resource for genetic discovery of novel variants that may not be found in the European population However research studies in non European populations are weakened by the lack of availability of large scale reference datasets and in particular genotype imputation panels Genotype imputation is a statistical methodology that uses observations of genotypes in a large reference panel to infer unobserved genotypes in a target dataset This methodology is widely used within GWAS and allows novel genetic associations to be identified and refined Due to this utility very large reference panels have been constructed containing thousands or tens of thousands of whole genome sequences Unfortunately the largest imputation panels are composed of predominantly European genomes reflecting the modern bias towards European studies in GWAS This proposal aims to address this imbalance by constructing an imputation panel specifically for the African American population In doing so we will expand andMe s ability to perform genetic discovery in non European populations and improve the understanding of global genetic variation underlying diseases and traits Key commercial outcomes of the research include the identification of novel genetic targets for internal and external therapeutic development The long term aim is to improve understanding of disease in minority populations which we hope may eventually lead to improved treatments of disease in these historically medically understudied groups Project Narrative Genome wide association studies have yielded many discoveries of genes associated with disease but the vast majority of such studies have been conducted in European populations This proposal aims to empower genetic research in non European populations by developing a reference dataset from targeted DNA sequencing of the diversity contained within the andMe research participant database This study will enable andMe and other researchers to better discover disease variants in individuals with non European ancestry with a particular focus on African American populations