Genomics and Biobank Research for Chronic Diseases

National Institute On Minority Health And Health Disparities

Investigators

Linked publications, trials & patents

Abstract

Current methods for genetic ancestry (GA) inference do not scale to biobank-size genomic datasets. We present Rye-a new algorithm for GA inference at biobank scale. We compared the accuracy and runtime performance of Rye to the widely used RFMix, ADMIXTURE and iAdmix programs and applied it to a dataset of 488221 genome-wide variant samples from the UK Biobank. Rye infers GA based on principal component analysis (PCA) of genomic variant samples from ancestral reference populations and query individuals. The algorithm's accuracy is powered by Metropolis-Hastings optimization and its speed is provided by non-negative least squares regression. Rye produces highly accurate GA estimates for three-way admixed populations-African, European and Native American-compared to RFMix and ADMIXTURE, and shows 50 runtime improvement compared to ADMIXTURE on the UK Biobank dataset. Development of version 2 of Rye, which supports a novel projection-based ancestry inference methods, and an unsupervised version of Rye, which infers ancestry for groups defined by unsupervised clustering of PCA data, have been initiated. We also developed the UK Biobank (UKB) Health Disparities Browser with the aims of (i) facilitating the exploration of the landscape of health disparities in the UK and (ii) directing the attention to areas of disparities research that might have the greatest public health impact. Health disparities were characterized for UKB participant groups defined by age, country of residence, ethnic group, sex and socioeconomic deprivation. We defined disease cohorts for UKB participants by mapping participant International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes to phenotype codes (phecodes). For each of the population attributes used to define population groups, disease percent prevalence values were computed for all groups from phecode case-control cohorts, and the magnitude of the disparities was calculated by both the difference and ratio of the range of disease prevalence values among groups to identify high- and low-prevalence disparities. We identified numerous diseases and health conditions with disparate prevalence values across population attributes, and we deployed an interactive web browser to visualize the results of our analysis: https://ukbatlas.health-disparities.org. The interactive browser includes overall and group-specific prevalence data for 1513 diseases based on a cohort of >500 000 participants from the UKB.