Publications

MOTIVATION

Local ancestry analysis of genotype data from recently admixed populations (e.g. Latinos, African Americans) provides key insights into population history and disease genetics. Although methods for local ancestry inference have been extensively validated in simulations (under many unrealistic assumptions), no empirical study of local ancestry accuracy in Latinos exists to date. Hence, interpreting findings that rely on local ancestry in Latinos is challenging.

RESULTS

Here, we use 489 nuclear families from the mainland USA, Puerto Rico and Mexico in conjunction with 3204 unrelated Latinos from the Multiethnic Cohort study to provide the first empirical characterization of local ancestry inference accuracy in Latinos. Our approach for identifying errors does not rely on simulations but on the observation that local ancestry in families follows Mendelian inheritance. We measure the rate of local ancestry assignments that lead to Mendelian inconsistencies in local ancestry in trios (MILANC), which provides a lower bound on errors in the local ancestry estimates. We show that MILANC rates observed in simulations underestimate the rate observed in real data, and that MILANC varies substantially across the genome. Second, across a wide range of methods, we observe that loci with large deviations in local ancestry also show enrichment in MILANC rates. Therefore, local ancestry estimates at such loci should be interpreted with caution. Finally, we reconstruct ancestral haplotype panels to be used as reference panels in local ancestry inference and show that ancestry inference is significantly improved by incoroprating these reference panels.

AVAILABILITY AND IMPLEMENTATION

We provide the reconstructed reference panels together with the maps of MILANC rates as a public resource for researchers analyzing local ancestry in Latinos at http://bogdanlab.pathology.ucla.edu

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

Antiretroviral therapy has greatly increased longevity for individuals with human immunodeficiency virus (HIV) infection. About 0.5% of patients with HIV infection develop moderate to severe pulmonary arterial hypertension, which is several thousand times higher than the incidence of idiopathic pulmonary arterial hypertension. As more than 30 million individuals are chronically infected, HIV infection could soon become one of the most common causes of pulmonary arterial hypertension worldwide. Pulmonary arterial hypertension is a relentlessly progressive disease leading to right heart failure and death. In this article the available data on epidemiology, hemodynamics, mechanisms, and therapeutic strategies for HIV-associated pulmonary arterial hypertension are reviewed.