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:BackgroundSentinel physician surveillance in communities has played an important role in detecting early signs of epidemics. The traditional approach is to let the primary care physician voluntarily and actively report diseases to the health department on a weekly basis. However, this is labor-intensive work, and the spatio-temporal resolution of the surveillance data is not precise at all. In this study, we built up a clinic-based enhanced sentinel surveillance system named "Sentinel plus" which was designed for sentinel clinics and community hospitals to monitor 23 kinds of syndromic groups in Taipei City, Taiwan. The definitions of those syndromic groups were based on ICD-10 diagnoses from physicians.MethodsDaily ICD-10 counts of two syndromic groups including ILI and EV-like syndromes in Taipei City were extracted from Sentinel plus. A negative binomial regression model was used to couple with lag structure functions to examine the short-term association between ICD counts and meteorological variables. After fitting the negative binomial regression model, residuals were further rescaled to Pearson residuals. We then monitored these daily standardized Pearson residuals for any aberrations from July 2018 to October 2019.ResultsThe results showed that daily average temperature was significantly negatively associated with numbers of ILI syndromes. The ozone and PM2.5 concentrations were significantly positively associated with ILI syndromes. In addition, daily minimum temperature, and the ozone and PM2.5 concentrations were significantly negatively associated with the EV-like syndromes. The aberrational signals detected from clinics for ILI and EV-like syndromes were earlier than the epidemic period based on outpatient surveillance defined by the Taiwan CDC.ConclusionsThis system not only provides warning signals to the local health department for managing the risks but also reminds medical practitioners to be vigilant toward susceptible patients. The near real-time surveillance can help decision makers evaluate their policy on a timely basis.

Project description:INTRODUCTION:Delaying care-seeking for tuberculosis (TB) symptoms is a major contributor to mortality, leading to worse outcomes and spread. To reduce delays, it is essential to identify barriers to care-seeking and target populations most at risk of delaying. Previous work identifies barriers only in people within the health system, often long after initial care-seeking. METHODS:We conducted a community-based survey of 84?625 households in Chennai, India, to identify 1667 people with TB-indicative symptoms in 2018-2019. Cases were followed prospectively to observe care-seeking behaviour. We used a comprehensive survey to identify care-seeking drivers, then performed multivariate analyses to identify care-seeking predictors. To identify profiles of individuals most at risk to delay care-seeking, we segmented the sample using unsupervised clustering. We then estimated the per cent of the TB-diagnosed population in Chennai in each segment. RESULTS:Delayed care-seeking characteristics include smoking, drinking, being employed, preferring different facilities than the community, believing to be at lower risk of TB and believing TB is common. Respondents who reported fever or unintended weight loss were more likely to seek care. Clustering analysis revealed seven population segments differing in care-seeking, from a retired/unemployed/disabled cluster, where 70% promptly sought care, to a cluster of employed men who problem-drink and smoke, where only 42% did so. Modelling showed 54% of TB-diagnosed people who delay care-seeking might belong to the latter segment, which is most likely to acquire TB and least likely to promptly seek care. CONCLUSION:Interventions to increase care-seeking should move from building general awareness to addressing treatment barriers such as lack of time and low-risk perception. Care-seeking interventions should address specific beliefs through a mix of educational, risk perception-targeting and social norms-based campaigns. Employed men who problem-drink and smoke are a prime target for interventions. Reducing delays in this group could dramatically reduce TB spread.

Dataset Information

Population Pharmacogenomics for Precision Public Health in Colombia.

Publications

Population Pharmacogenomics for Precision Public Health in Colombia.

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