What does genomic medicine mean for diverse populations?
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ABSTRACT:
SUBMITTER: Adeyemo A
PROVIDER: S-EPMC3907917 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
Publications
What does genomic medicine mean for diverse populations?
Adeyemo Adebowale A Rotimi Charles C
Molecular genetics & genomic medicine 20140110 1
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Project description:BackgroundPopulation-based genomic screening has the predicted ability to reduce morbidity and mortality associated with medically actionable conditions. However, much research is needed to develop standards for genomic screening and to understand the perspectives of people offered this new testing modality. This is particularly true for non-European ancestry populations who are vastly underrepresented in genomic medicine research. Therefore, we implemented a pilot genomic screening program in the BioMe Biobank in New York City, where the majority of participants are of non-European ancestry.MethodsWe initiated genomic screening for well-established genes associated with hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), and familial hypercholesterolemia (FH). We evaluated and included an additional gene (TTR) associated with hereditary transthyretin amyloidosis (hATTR), which has a common founder variant in African ancestry populations. We evaluated the characteristics of 74 participants who received results associated with these conditions. We also assessed the preferences of 7461 newly enrolled BioMe participants to receive genomic results.ResultsIn the pilot genomic screening program, 74 consented participants received results related to HBOC (N = 26), LS (N = 6), FH (N = 8), and hATTR (N = 34). Thirty-three of 34 (97.1%) participants who received a result related to hATTR were self-reported African American/African (AA) or Hispanic/Latinx (HL), compared to 14 of 40 (35.0%) participants who received a result related to HBOC, LS, or FH. Among the 7461 participants enrolled after the BioMe protocol modification to allow the return of genomic results, 93.4% indicated that they would want to receive results. Younger participants, women, and HL participants were more likely to opt to receive results.ConclusionsThe addition of TTR to a pilot genomic screening program meant that we returned results to a higher proportion of AA and HL participants, in comparison with genes traditionally included in genomic screening programs in the USA. We found that the majority of participants in a multi-ethnic biobank are interested in receiving genomic results for medically actionable conditions. These findings increase knowledge about the perspectives of diverse research participants on receiving genomic results and inform the broader implementation of genomic medicine in underrepresented patient populations.
| S-EPMC7863616 | biostudies-literature
Project description:In the North-Central United States, lowland ecotype switchgrass can increase yield by up to 50% compared with locally adapted but early flowering cultivars. However, lowland ecotypes are not winter tolerant. The mechanism for winter damage is unknown but previously has been associated with late flowering time. This study investigated heading date (measured for two years) and winter survivorship (measured for three years) in a multi-generation population generated from two winter-hardy lowland individuals and diverse southern lowland populations. Sequencing data (311,776 markers) from 1,306 individuals were used to evaluate genome-wide trait prediction through cross-validation and progeny prediction (n = 52). Genetic variance for heading date and winter survivorship was additive with high narrow-sense heritability (0.64 and 0.71, respectively) and reliability (0.68 and 0.76, respectively). The initial negative correlation between winter survivorship and heading date degraded across generations (F1r = -0.43, pseudo-F2r = -0.28, pseudo-F2 progeny r = -0.15). Within-family predictive ability was moderately high for heading date and winter survivorship (0.53 and 0.52, respectively). A multi-trait model did not improve predictive ability for either trait. Progeny predictive ability was 0.71 for winter survivorship and 0.53 for heading date. These results suggest that lowland ecotype populations can obtain sufficient survival rates in the northern United States with two or three cycles of effective selection. Despite accurate genomic prediction, naturally occurring winter mortality successfully isolated winter tolerant genotypes and appears to be an efficient method to develop high-yielding, cold-tolerant switchgrass cultivars.
| S-EPMC9997553 | biostudies-literature
Project description:Mexico is developing the basis for genomic medicine to improve healthcare of its population. The extensive study of genetic diversity and linkage disequilibrium structure of different populations has made it possible to develop tagging and imputation strategies to comprehensively analyze common genetic variation in association studies of complex diseases. We assessed the benefit of a Mexican haplotype map to improve identification of genes related to common diseases in the Mexican population. We evaluated genetic diversity, linkage disequilibrium patterns, and extent of haplotype sharing using genomewide data from Mexican Mestizos from regions with different histories of admixture and particular population dynamics. Ancestry was evaluated by including 1 Mexican Amerindian group and data from the HapMap. Our results provide evidence of genetic differences between Mexican subpopulations that should be considered in the design and analysis of association studies of complex diseases. In addition, these results support the notion that a haplotype map of the Mexican Mestizo population can reduce the number of tag SNPs required to characterize common genetic variation in this population. This is one of the first genomewide genotyping efforts of a recently admixed population in Latin America.
| S-EPMC2680428 | biostudies-literature
Project description:This study is a multi-site randomized, controlled trial testing the effect of a combined intervention that includes a colorectal cancer (CRC) screening decision aid plus patient navigation in a diverse, primary care patient population in clinical sites in North Carolina and New Mexico.
Our primary aim is to determine the effect of the intervention on CRC screening completion six months after the index visit among all enrolled participants and among Latinos. Secondarily, we will determine how this intervention affects screening-related knowledge, self-efficacy, intent, and clinical communication, and examine whether these factors mediate the effect of the intervention on screening test completion. Lastly, we will explore whether insurance status, ethnicity, and patient language preference moderate the effect of the intervention on screening.
| 2160185 | ecrin-mdr-crc
Project description:Genomic prediction is a useful tool to accelerate genetic gain in selection using DNA marker information. However, this technology typically relies on standard prediction procedures, such as genomic BLUP, that are not designed to accommodate population heterogeneity resulting from differences in marker effects across populations. In this study, we assayed different prediction procedures to capture marker-by-population interactions in genomic prediction models. Prediction procedures included genomic BLUP and two kernel-based extensions of genomic BLUP which explicitly accounted for population heterogeneity. To model population heterogeneity, dissemblance between populations was either depicted by a unique coefficient (as previously reported), or a more flexible function of genetic distance between populations (proposed herein). Models under investigation were applied in a diverse switchgrass sample under two validation schemes: whole-sample calibration, where all individuals except selection candidates are included in the calibration set, and cross-population calibration, where the target population is entirely excluded from the calibration set. First, we showed that using fixed effects, from principal components or putative population groups, appeared detrimental to prediction accuracy, especially in cross-population calibration. Then we showed that modeling population heterogeneity by our proposed procedure resulted in highly significant improvements in model fit. In such cases, gains in accuracy were often positive. These results suggest that population heterogeneity may be parsimoniously captured by kernel methods. However, in cases where improvement in model fit by our proposed procedure is null-to-moderate, ignoring heterogeneity should probably be preferred due to the robustness and simplicity of the standard genomic BLUP model.
| S-EPMC6404615 | biostudies-other
Project description:The development of precision medicine strategies requires prior knowledge of the genetic background of the target population. However, despite the availability of data from admixed Americans within large reference population databases, we cannot use these data as a surrogate for that of the Brazilian population. This lack of transferability is mainly due to differences between ancestry proportions of Brazilian and other admixed American populations. To address the issue, a coalition of research centres created the Brazilian Initiative on Precision Medicine (BIPMed). In this study, we aim to characterise two datasets obtained from 358 individuals from the BIPMed using two different platforms: whole-exome sequencing (WES) and a single nucleotide polymorphism (SNP) array. We estimated allele frequencies and variant pathogenicity values from the two datasets and compared our results using the BIPMed dataset with other public databases. Here, we show that the BIPMed WES dataset contains variants not included in dbSNP, including 6480 variants that have alternative allele frequencies (AAFs) >1%. Furthermore, after merging BIPMed WES and SNP array data, we identified 809,589 variants (47.5%) not present within the 1000 Genomes dataset. Our results demonstrate that, through the incorporation of Brazilian individuals into public genomic databases, BIPMed not only was able to provide valuable knowledge needed for the implementation of precision medicine but may also enhance our understanding of human genome variability and the relationship between genetic variation and disease predisposition.
| S-EPMC7532430 | biostudies-literature
Project description:The concept of 'evidence-based medicine' dates back to mid-19th century or even earlier. It remains pivotal in planning, funding and in delivering the health care. Clinicians, public health practitioners, health commissioners/purchasers, health planners, politicians and public seek formal 'evidence' in approving any form of health care provision. Essentially 'evidence-based medicine' aims at the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients. It is in fact the 'personalised medicine' in practice. Since the completion of the human genome project and the rapid accumulation of huge amount of data, scientists and physicians alike are excited on the prospect of 'personalised health care' based on individual's genotype and phenotype. The first decade of the new millennium now witnesses the transition from 'evidence-based medicine' to the 'genomic medicine'. The practice of medicine, including health promotion and prevention of disease, stands now at a wide-open road as the scientific and medical community embraces itself with the rapidly expanding and revolutionising field of genomic medicine. This article reviews the rapid transformation of modern medicine from the 'evidence-based medicine' to 'genomic medicine'.
| S-EPMC2269034 | biostudies-other
Project description:To characterize the extent and impact of ancestry-related biases in precision genomic medicine, we use 642 whole-genome sequences from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) project to evaluate typical filters and databases. We find significant correlations between estimated African ancestry proportions and the number of variants per individual in all variant classification sets but one. The source of these correlations is highlighted in more detail by looking at the interaction between filtering criteria and the ClinVar and Human Gene Mutation databases. ClinVar's correlation, representing African ancestry-related bias, has changed over time amidst monthly updates, with the most extreme switch happening between March and April of 2014 (r=0.733 to r=-0.683). We identify 68 SNPs as the major drivers of this change in correlation. As long as ancestry-related bias when using these clinical databases is minimally recognized, the genetics community will face challenges with implementation, interpretation and cost-effectiveness when treating minority populations.
| S-EPMC5062569 | biostudies-literature
Project description:Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.
| S-EPMC5710841 | biostudies-literature
Project description:Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African Americans and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarin-related adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype-guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry. Despite differing frequencies of variants by race/ethnicity, most evidence in diverse populations evaluates variants that are most common in populations of European ancestry. Algorithms that do not include variants important across race/ethnic groups are unlikely to benefit diverse populations. In some race/ethnic groups, development of race-specific or admixture-based algorithms may facilitate improved genotype-guided warfarin dosing algorithms above and beyond that seen in individuals of European ancestry. These observations should be considered in the interpretation of literature evaluating the clinical utility of genotype-guided warfarin dosing. Careful consideration of race/ethnicity and additional evidence focused on improving warfarin dosing algorithms across race/ethnic groups will be necessary for successful clinical implementation of warfarin pharmacogenomics. The evidence for warfarin pharmacogenomics has a broad significance for pharmacogenomic testing, emphasizing the consideration of race/ethnicity in discovery of gene-drug pairs and development of clinical recommendations for pharmacogenetic testing.
| S-EPMC6913521 | biostudies-literature