Dataset Information

Population Pharmacogenomics for Precision Public Health in Colombia.

ABSTRACT: While genomic approaches to precision medicine hold great promise, they remain prohibitively expensive for developing countries. The precision public health paradigm, whereby healthcare decisions are made at the level of populations as opposed to individuals, provides one way for the genomics revolution to directly impact health outcomes in the developing world. Genomic approaches to precision public health require a deep understanding of local population genomics, which is still missing for many developing countries. We are investigating the population genomics of genetic variants that mediate drug response in an effort to inform healthcare decisions in Colombia. Our work focuses on two neighboring populations with distinct ancestry profiles: Antioquia and Chocó. Antioquia has primarily European genetic ancestry followed by Native American and African components, whereas Chocó shows mainly African ancestry with lower levels of Native American and European admixture. We performed a survey of the global distribution of pharmacogenomic variants followed by a more focused study of pharmacogenomic allele frequency differences between the two Colombian populations. Worldwide, we found pharmacogenomic variants to have both unusually high minor allele frequencies and high levels of population differentiation. A number of these pharmacogenomic variants also show anomalous effect allele frequencies within and between the two Colombian populations, and these differences were found to be associated with their distinct genetic ancestry profiles. For example, the C allele of the single nucleotide polymorphism (SNP) rs4149056 [Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1)?5], which is associated with an increased risk of toxicity to a commonly prescribed statin, is found at relatively high frequency in Antioquia and is associated with European ancestry. In addition to pharmacogenomic alleles related to increased toxicity risk, we also have evidence that alleles related to dosage and metabolism have large frequency differences between the two populations, which are associated with their specific ancestries. Using these findings, we have developed and validated an inexpensive allele-specific PCR assay to test for the presence of such population-enriched pharmacogenomic SNPs in Colombia. These results serve as an example of how population-centered approaches to pharmacogenomics can help to realize the promise of precision medicine in resource-limited settings.

SUBMITTER: Nagar SD

PROVIDER: S-EPMC6439339 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Population Pharmacogenomics for Precision Public Health in Colombia.

Nagar Shashwat Deepali SD Moreno A Melissa AM Norris Emily T ET Rishishwar Lavanya L Conley Andrew B AB O'Neal Kelly L KL Vélez-Gómez Sara S Montes-Rodríguez Camila C Jaraba-Álvarez Wendy V WV Torres Isaura I Medina-Rivas Miguel A MA Valderrama-Aguirre Augusto A Jordan I King IK Gallo Juan Esteban JE

Frontiers in genetics 20190322

While genomic approaches to precision medicine hold great promise, they remain prohibitively expensive for developing countries. The precision public health paradigm, whereby healthcare decisions are made at the level of populations as opposed to individuals, provides one way for the genomics revolution to directly impact health outcomes in the developing world. Genomic approaches to precision public health require a deep understanding of local population genomics, which is still missing for man ...[more]

PMID: 30967898

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Project description:BackgroundFilipino Americans (FAs) are the third-largest Asian American subgroup in the United States (US). Some studies showed that FAs experience more cardiometabolic diseases (CMDs) than other Asian subgroups and non-Hispanic Whites. The increased prevalence of CMD observed in FAs could be due to genetics and social/dietary lifestyles. While FAs are ascribed as an Asian group, they have higher burdens of CMD, and adverse social determinants of health compared to other Asian subgroups. Therefore, studies to elucidate how FAs might develop CMD and respond to medications used to manage CMD are warranted. The ultimate goals of this study are to identify potential mechanisms for reducing CMD burden in FAs and to optimize therapeutic drug selection. Collectively, these investigations could reduce the cardiovascular health disparities among FAs.Rationale and designThis is a cross-sectional epidemiological design to enroll 300 self-identified Filipino age 18 yrs. or older without a history of cancer and/or organ transplant from Virginia, Washington DC, and Maryland. Once consented, a health questionnaire and disease checklist are administered to participants, and anthropometric data and other vital signs are collected. When accessible, we collect blood samples to measure basic blood biochemistry, lipids, kidney, and liver functions. We also extract DNA from the blood or saliva for genetic and pharmacogenetic analyses. CMD prevalence in FAs will be compared to the US population. Finally, we will conduct multivariate analyses to ascertain the role of genetic and non-genetic factors in developing CMD in FAs. Virginia Commonwealth University IRB approved all study materials (Protocol HM20018500).SummaryThis is the first community-based study to involve FAs in genomics research. The study is actively recruiting participants. Participant enrollment is ongoing. At the time of this publication, the study has enrolled 97 participants. This ongoing study is expected to inform future research to reduce cardiovascular health disparities among FAs.

Dataset Information

Population Pharmacogenomics for Precision Public Health in Colombia.

Publications

Population Pharmacogenomics for Precision Public Health in Colombia.

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