Evaluating the relationships between genetic ancestry and the clinical phenome

In this study, we leverage the biobank from Vanderbilt University Medical Center, BioVU, to investigate relationships between genetic ancestry proportion and the clinical phenome. For all samples in BioVU, we calculated six ancestry proportions based on 1000 Genomes references: eastern African (EAFR), western African (WAFR), northern European (NEUR), southern European (SEUR), eastern Asian (EAS), and southern Asian (SAS). From PheWAS, we found phecode categories significantly enriched neoplasms for EAFR, WAFR, and SEUR, and pregnancy complication in SEUR, NEUR, SAS, and EAS (p < 0.003). We then selected phenotypes hypertension (HTN) and atrial fibrillation (AFib) to further investigate the relationships between these phenotypes and EAFR, WAFR, SEUR, and NEUR using logistic regression modeling and non-linear restricted cubic spline modeling (RCS). For EAS and SAS, we chose renal failure (RF) for further modeling. The relationships between HTN and AFib and the ancestries EAFR, WAFR, and SEUR were best fit by the linear model (beta p < 1x10-4 for all) while the relationships with NEUR were best fit with RCS (HTN ANOVA p = 0.001, AFib ANOVA p < 1x10-4). For RF, the relationship with SAS was best fit with a linear model (beta p < 1x10-4) while RCS model was a better fit for EAS (ANOVA p < 1x10-4). In this study, we identify relationships between genetic ancestry and phenotypes that are best fit with non-linear modeling techniques. The assumption of linearity for reg...
Source: Pacific Symposium on Biocomputing - Category: Bioinformatics Authors: Source Type: research