Abstract: Admixed populations (such as African Americans and Latinos) are of special interest in human genetics because they allow us to test for both ancestry effects via admixture mapping and genotype effects via association mapping, especially diseases such as asthma that show racial differences in prevalence and allele frequency across populations. Despite advances in asthma care, African Americans are four times more likely to be hospitalized and five times more likely to die from asthma than European Americans. However, most genetic studies have primarily been conducted in European ancestry populations.
In this study, 1600 asthmatic and 1000 healthy controls of African American samples were genotyped using the Multi-Ethnic Genotyping Array (MEGA), genotype imputation was carried out with TOPMed reference panel using the Michigan Imputation Server. Global and local ancestry estimation were carried out using the RFMix v2, a powerful discriminative modeling approach. Logistic regression models using the number of copies of local ancestry at each locus and the binary asthma-genotype correlation adjusted for the covariates were used for admixture mapping and association mapping, respectively. Joint admixture and association were tested using the BMIX, an approach that combines admixture and association statistics at single markers.
Both admixture and association analysis identified novel genetic risk variants associated with asthma including loci specific to African ancestry. Additional analysis including variant prioritization and functional annotation, statistical and clinical challenges, and opportunities of mixed ancestry populations in the context of big multi-omics data and racial disparities will be discussed.
Short Bio:Tesfaye Mersha is an associate professor at the Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine. His research combines quantitative, ancestry and statistical genomics to unravel genetic and non-genetic contributions to complex diseases and racial disparities in human populations, particularly asthma and asthma-related allergic disorders.
Mersha is a recognized expert in the field of genetic ancestry, race, ethnicity, admixture mapping and mining functional genomic databases related to complex diseases. Among his significant contributions, his team developed AncestrySNPminer, the first web-based bioinformatics tool to retrieve ancestry-informative markers from the genomic databases.
His long-term research goal is to understand and dissect how biologic predisposition and environmental exposures interact to shape racial disparities in complex disorders. Some of his recent work including the question: “Do allergy-related readmissions differ by degree of ancestry, and would this association be explained by socio-environmental risk factors rather than direct biologic effects of ancestry on asthma?” In addition, he explores link between COVID-19 pandemic, other health conditions, chronic exposure to air pollution in the context of racial disparities and global variations.
Dr. Mersha received multiple awards and honors, including a Faculty Research Achievement Award from Cincinnati Children’s Hospital Medical Center, Keystone Symposia Early Career Investigator Award and African Professionals Network Business and Professional Achievement Award. His research is continuously funded by the National Institute of Health (NIH).