Geospatial distribution and population substructure of subgroups of US ethnic minorities: implications for perpetuation of health disparities and paucity of precision medicine

Substructure due to familial-associated divisions exists in all large populations. Geographical heterogeneity in US ethnic minorities is a function of historical, social, political, and economic factors overlaying regional geographical biodiversity. Using geospatial, historical, demographic, genetic, and epidemiological databases, we identify 40 US microethnic isolates across the US, the “minorities within ethnic minorities” and locate their geospatial distributions within the US. Key components of the environment relevant to health disparities are identified and elaborated in terms of their impact on genomics. US ethnic minority microethnic isolates often have distinct genetic and social histories from the US ethnic majority that put these isolates at a disadvantage in the quest for access to relevant, precision medicine because of the magnitude of imbedded (North Atlantic Euro-American) bias in the existing databases. However, these microethnic isolates are also at a disadvantage when simply aggregated with their nearest ethnic minority macroethnic group (e.g., generic African American). The use of geospatial and ethnographic analyses has the potential to accelerate the accurate identification of heretofore disadvantaged subgroups of ethnic minority groups, bringing them into the mainstream of genomic diversity studies and healthcare acces

A Narrative Review of Maternal Depression Research Focusing on Women of Caribbean Descent in the Diaspora and Caribbean Women in the Region

Maternal depression is a global public health issue (Almond, 2009); however, much of the existing research on conditions like the ‘baby blues’ and postpartum depression have been conducted with White women in North America and Europe. This narrative review seeks to expand the scope of maternal depression research by including and analyzing maternal depression studies conducted with Caribbean descent women living in the Diaspora and women in the English-speaking Caribbean alongside some of the work from North America and Europe. Through this engagement with the existing research three thematic areas emerged. These are: widely used prevalence and incidence rates of the ‘baby blues’ and postpartum depression which do not reflect rates in the Caribbean and other developing countries; distinct explanatory models which help Caribbean descent women understand postpartum depression and are informed by their social, cultural, and historical contexts; and the question of how Caribbean women’s diverse social realities and identities have been grappled with by researchers doing work in this area. The major feature that crosscuts these thematic areas is the fact of difference. This is exemplified by the Intersectional identities of Caribbean descent women in the Diaspora and region which helps to vary the data on maternal depression and present a fuller representation of women’s experiences with conditions like the ‘baby blues’ and postpartum depression. Collectively, the findings of this review reinforce the notion that “Caribbeanness” must take into account the multiple identities and experiences Caribbean women negotiate historically and contemporarily. The paper concludes with further engagement with this fact of difference, and a discussion about what kinds of interventions and conceptual/theoretical tools may be useful to advancing the study of maternal depression amongst Caribbean women in the Diaspora and region

Ethnogenetic Layering as an Alternative to the Race Model

Background: Traditionally, studies in human biodiversity, disease risk, and health disparities have defined populations in the context of typological racial models. However, such racial models are often imprecise generalizations that fail to capture important local patterns of human biodiversity. Aim: More explicit, detailed, and integrated information on relevant geographic, environmental, cultural, genetic, historical, and demographic variables are needed to understand local group expressions of disease inequities. This paper details the methods used in ethnogenetic layering (EL), a non-typological alternative to the current reliance of the biological racial paradigm in public health, epidemiology, and biomedicine. Subjects and methods: EL is focused on geographically identified microethnic groups or MEGs, a more nuanced and sensitive level of analysis than race. Using the MEG level of analysis, EL reveals clinical variations, details the causes of health disparities, and provides a foundation for bioculturally effective intervention strategies. EL relies on computational approaches by using GIS-facilitated maps to produce horizontally stratified geographical regional profiles which are then stacked and evaluated vertically. Each horizontal digital map details local geographic variation in the attributes of a particular database; usually this includes data on local historical demography, genetic diversity, cultural patterns, and specific chronic disease risks (e.g. dietary and toxicological exposures). Horizontal visual display of these layered maps permits vertical analysis at various geographic hot spots. Results and conclusions: From these analyses, geographical areas and their associated MEGs with highly correlated chronic disease risk factors can be identified and targeted for further study

Correction: African American mitochondrial DNAs often match mtDNAs found in multiple African ethnic groups

After the publication of this work [1], we became aware that AFDIL data set used to construct our database of sub-Saharan mtDNA sequences had been mislabelled, and in fact, did not contain Sierra Leone mtDNA sequences. We have obtained the correct Sierra Leone data set from AFDIL, reconstructed the database using the new file, and reanalyzed all of the data. The size of our database was reduced from 3725 to 3717 since the new Sierra Leone data set contained 109 sequences instead of 117 in themislabelled data set. The swapping of data sets resulted in a cascade of minor corrections to Tables 2, 3, 4, 5, and 6 (see below). We also corrected an error in the entry for BAM013 in Table 7. However, the only major change was that there were a number of matches of African-American sequences to sequences in the mislabelled data set. Thus, the number of African-American matches to single ethnic groups dropped from a total of 16 to 9 (Table 3) representing just 5% of the African American sequences that we compared to the database

Cancer in an Historic Washington DC African American Population and Its Geospatial Distribution

Background: Cancer continues to be a major cause of morbidity and mortality in the African American community but insights into the types and incidence of cancer 85 years ago have been virtually non-existent and little is known of its geospatial distribution. Historical information on cancer can shed light on current health disparities, particularly among African Americans.Objective: The aims of this study were to: (1) assess the frequencies of the cancer types present among Cobb Collection individuals; (2) compare these data with current research on cancer in African Americans; and (3) evaluate the pattern of cancer expression, including its geospatial distributions, as a cause of death between 1931 and 1969 in an historic African American subgroup and compare this pattern with the historic and contemporary patterns of cancer etiology and incidence.Methods: Systematic assessments of the existing clinical, demographic, and anatomical records in the Cobb Research Laboratory were made of individuals identified as dying from specific cancers from 1931 to 1969. These were compared with the national profiles of cancer during the historic time an individual died as well as the contemporary patterns of cancer deaths. Analysis of their residential addresses just prior to death were assessed using a commercial geographic information system. Each location was assigned a geospatial location and proximity between each site and clusters of sites were investigated.Results: Seventeen different cancer types were found within 28 individuals of the Cobb Collection between 1931 and 1969. The cancer types with the highest frequencies were carcinoma of stomach, lung, esophagus, larynx and bronchogenic carcinoma. Eighty-four percent of all cancer incidents occurred in males and 76% were among individuals identified as African American. Seventy-one percent of the highest incidence cancers were among African American males. Geospatial clustering was observed most noticeably in the redistribution of carcinoma of the esophagus.Conclusion: Our results provide historical depth to our knowledge of the common cancer causes of morbidity among African Americans of Washington DC from 1931 to 1969. We contrast these findings with national historical data on cancer etiology and ethnic disparities in incidence. Our study suggests that historic data can provide longitudinal depth to our understanding of the persistence of cancer susceptibilities in a vulnerable subgroup

Core issues, case studies, and the need for expanded Legacy African American genomics

Introduction: Genomic studies of Legacy African Americans have a tangled and convoluted history in western science. In this review paper, core issues affecting African American genomic studies are addressed and two case studies, the New York African Burial Ground and the Gullah Geechee peoples, are presented to highlight the current status of genomic research among Africa Americans.Methods: To investigate our target population’s core issues, a metadatabase derived from 22 publicly accessible databases were reviewed, evaluated, and synthesized to identify the core bioethical issues prevalent during the centuries of the African American presence in North America. The sequence of metadatabase development included 5 steps: identification of information, record screening and retention of topic relevant information, identification of eligibility via synthesis for concept identifications, and inclusion of studies used for conceptual summaries and studies used for genetic and genomic summaries. To these data we added our emic perspectives and specific insights from our case studies.Results: Overall, there is a paucity of existing research on underrepresent African American genomic diversity. In every category of genomic testing (i.e., diagnostic, clinical predictive, pharmacogenomic, direct-to-consumer, and tumor testing), African Americans are disproportionately underrepresented compared to European Americans. The first of our case studies is from the New York African Burial Ground Project where genomic studies of grave soil derived aDNA yields insights into the causes of death of 17th and 18th Century African Americans. In the second of our case studies, research among the Gullah Geechee people of the Carolina Lowcountry reveals a connection between genomic studies and health disparities.Discussion: African Americans have historically borne the brunt of the earliest biomedical studies used to generate and refine primitive concepts in genetics. As exploited victims these investigations, African American men, women, and children were subjected to an ethics-free western science. Now that bioethical safeguards have been added, underrepresented and marginalized people who were once the convenient targets of western science, are now excluded from its health-related benefits. Recommendations to enhance the inclusion of African Americans in global genomic databases and clinical trials should include the following: emphasis on the connection of inclusion to advances in precision medicine, emphasis on the relevance of inclusion to fundamental questions in human evolutionary biology, emphasis on the historical relevance of inclusion for Legacy African Americans, emphasis on the ability of inclusion to foster expanded scientific expertise in the target population, ethical engagement with their descendants, and increase the number of science researchers from these communities

Applications of natural products in the control of mosquito-transmitted diseases

Mosquito-transmitted diseases remain one of the most significant causes of mortality in the African continent, despite successes in controlling these diseases in other regions of the world. The disproportionate impact in areas of poverty suggests a need for control that is efficient and does not require complex technological control strategies. Focusing on the vectors of disease, the mosquito, there are many alternatives to synthetic, chemical pesticides that await discovery and development. Although some natural products have been described, there is still a need for continuing research that incorporates endogenous knowledge in the selection process for potential vector control candidates. Recent experiments using natural products are summarized. Ultimately, a paradigm shift in research that evaluates natural products in a comparative manner will help to produce new materials for effective and efficient control of vectors and thereby achieve sustainable reduction of the impacts from the diseases they carry

African-American mitochondrial DNAs often match mtDNAs found in multiple African ethnic groups

BACKGROUND: Mitochondrial DNA (mtDNA) haplotypes have become popular tools for tracing maternal ancestry, and several companies offer this service to the general public. Numerous studies have demonstrated that human mtDNA haplotypes can be used with confidence to identify the continent where the haplotype originated. Ideally, mtDNA haplotypes could also be used to identify a particular country or ethnic group from which the maternal ancestor emanated. However, the geographic distribution of mtDNA haplotypes is greatly influenced by the movement of both individuals and population groups. Consequently, common mtDNA haplotypes are shared among multiple ethnic groups. We have studied the distribution of mtDNA haplotypes among West African ethnic groups to determine how often mtDNA haplotypes can be used to reconnect Americans of African descent to a country or ethnic group of a maternal African ancestor. The nucleotide sequence of the mtDNA hypervariable segment I (HVS-I) usually provides sufficient information to assign a particular mtDNA to the proper haplogroup, and it contains most of the variation that is available to distinguish a particular mtDNA haplotype from closely related haplotypes. In this study, samples of general African-American and specific Gullah/Geechee HVS-I haplotypes were compared with two databases of HVS-I haplotypes from sub-Saharan Africa, and the incidence of perfect matches recorded for each sample. RESULTS: When two independent African-American samples were analyzed, more than half of the sampled HVS-I mtDNA haplotypes exactly matched common haplotypes that were shared among multiple African ethnic groups. Another 40% did not match any sequence in the database, and fewer than 10% were an exact match to a sequence from a single African ethnic group. Differences in the regional distribution of haplotypes were observed in the African database, and the African-American haplotypes were more likely to match haplotypes found in ethnic groups from West or West Central Africa than those found in eastern or southern Africa. Fewer than 14% of the African-American mtDNA sequences matched sequences from only West Africa or only West Central Africa. CONCLUSION: Our database of sub-Saharan mtDNA sequences includes the most common haplotypes that are shared among ethnic groups from multiple regions of Africa. These common haplotypes have been found in half of all sub-Saharan Africans. More than 60% of the remaining haplotypes differ from the common haplotypes at a single nucleotide position in the HVS-I region, and they are likely to occur at varying frequencies within sub-Saharan Africa. However, the finding that 40% of the African-American mtDNAs analyzed had no match in the database indicates that only a small fraction of the total number of African haplotypes has been identified. In addition, the finding that fewer than 10% of African-American mtDNAs matched mtDNA sequences from a single African region suggests that few African Americans might be able to trace their mtDNA lineages to a particular region of Africa, and even fewer will be able to trace their mtDNA to a single ethnic group. However, no firm conclusions should be made until a much larger database is available. It is clear, however, that when identical mtDNA haplotypes are shared among many ethnic groups from different parts of Africa, it is impossible to determine which single ethnic group was the source of a particular maternal ancestor based on the mtDNA sequence

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation