So many Nigerians: why is Nigeria overrepresented as the ancestral genetic homeland of Legacy African North Americans?

The genetics of African North Americans are complex amalgamations of various West and Central African peoples with modest gene flow from specific European and Amerindian peoples. A comprehensive understanding of African North American biohistory is a prerequisite for accurate interpretations of the ancestral genetics of this population. Too often, genetic interpretations falter with ahistorical reconstructions. The recently reported overrepresentation of Nigerian lineages in African North Americans reflects pronounced limitations in the African genomic database, the artificiality of the colonial maps of Africa, the contributions of multiple African empires and kingdoms into the transatlantic trade in enslaved Africans, and the overrepresentation of Yoruba peoples in the existing limited representation of West Africans in public genomic databases. This Matters Arising paper is in response to Micheletti et al. (2020), published in The American Journal of Human Genetics. See also the response by Micheletti et al. (2020), published in this issue.

Not just in the past: Racist and sexist biases still permeate biology, anthropology, medicine, and education.

In the past decades, it has been increasingly recognized that some areas of science, such as anthropology, have been plagued by racist, Western-centric, and/or sexist biases. Unfortunately, an acculturation process to racism and sexism has been occurring for generations leading to systemic inequities that will take a long time to disappear. Here, we highlight the existence of current examples of racism, Western-centrism and sexism within: (1) the most popular anatomical atlases used in biological, anthropological and medical education; (2) prominent natural history museums and World Heritage Sites; (3) biological and anthropological scientific research publications; and (4) popular culture and influential children's books and educational materials concerning human biology and evolution.

Symptomatic, clinical and biomarker associations for mortality in hospitalized COVID-19 patients enriched for African Americans.

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected. RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, EA and AS were 14.8, 7.3, 16.3 and 2.2%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation (p = 0.001), shortness of breath (SOB) (p < 0.01), fatigue (p = 0.04), diarrhea (p = 0.02), and increased AST (p < 0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables among the demographics of study population were age (over 45 years old), male sex, EA, and patients hospitalized in New York. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID-19 death in our cohort. CONCLUSION: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, our study findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to high frequency of comorbidities and older age among AA. Glucocorticoids should be used carefully considering the poor outcomes associated with it. Special focus in treating patients with elevated liver enzymes and other inflammatory biomarkers such as CRP, troponin, ferritin, procalcitonin, and D-dimer are required to prevent poor outcomes.

Evolutionary perspectives on African North American genetic diversity: Origins and prospects for future investigations.

African-descended peoples of the Americas represent an amalgamation of West, Central, and Southeast African regional and ethnic groups with modest gene flow from specific non-African populations. Despite 16+ generations of residence in the Americas, there is a deficit of evolutionary knowledge about these populations. Focusing on Legacy African American, the African North American descendants of survivors of the transatlantic trade in enslaved Africans, we report on emic evolutionary perspectives of their self-identity gleaned from our interviews of 600 individuals collected over 2 years. Gullah-Geechee peoples of Carolina Coastal regions are a model case study due to their historical antiquity, substantial African retentions, relative geospatial isolation, and proposed progenitor status to other Legacy African American microethnic groups. We identify salient research questions for future studies that will begin to bridge the evolutionary gaps in our knowledge of these diverse peoples and the historical evidence for specific evolutionary processes.

Historical overview, current research, and emerging bioethical guidelines in researching the New York African burial ground.

OBJECTIVES: The issues addressed in this article are those related to the bioethical actions and decisions surrounding the excavation of the New York African Burial Ground (NYABG) in the 1990s, the significance of conducting research on historical African/African American remains, and the eminence of protecting newly discovered African American burial sites in the future for research purposes. MATERIALS AND METHODS: Skeletal (n = 419, at the time of excavation) and soil (n = 92) remains of the 17th and 18th century New York African Burial Ground were used to discuss the necessity of research on historical African/African American remains. DISCUSSION: Studying the remains of enslaved Africans is critical to understanding the biological processes and existence of all people. Researching the NYABG site, the oldest and largest burial site of free and enslaved Africans, illuminates the necessity and significance of scientific research on other historical African/African American cemeteries throughout the nation. The results of future research will provide a more profound sense of identity for a group of people who were forcefully severed from their genetic and cultural origins. This research will increase the representation of African descended people in genomic, anthropological, and cultural research, and ultimately help researchers to learn more about the origins of all humans.

What could you do with 400 years of biological history on african americans? Evaluating the potential scientific benefit of systematic studies of dental and skeletal materials on African Americans from the 17th through 20th centuries.

OBJECTIVES: How important is it to be able to reconstruct the lives of a highly diverse, historically recent macroethnic group over the course of 400 years? How many insights into human evolutionary biology and disease susceptibilities could be gained, even with this relatively recent window into the past? In this article, we explore the potential ramifications of a newly constructed dataset of Four Centuries of African American Biological Variation (4Cs). METHODS: This article provides initial lists of digitized variables formatted as SQL tables for the 17th and 18th century samples and for the 19th and 20th century samples. RESULTS: This database is dynamic and new information is added yearly. The database provides novel opportunities for significant insights into the past biological history of this group and three case study applications are detailed for comparative computational systems biology studies of (1) hypertension, (2) the oral microbiome, and (3) mental health disorders. CONCLUSIONS: The 4Cs dataset is ideal for interdisciplinary "next generation" science research and these data represent a unique step toward the accumulation of historically contextualized Big Data on an underrepresented group known to have experienced differential survival over time. Am. J. Hum. Biol. 28:510-513, 2016. © 2016 The Authors American Journal of Human Biology Published byWiley Periodicals, Inc.

African Americans Possessed High Prevalence of Comorbidities and Frequent Abdominal Symptoms, and Comprised A Disproportionate Share of Covid-19 Mortality among 9,873 Us- Hospitalized Patients Early in the Pandemic.

Background and aim: Identifying clinical characteristics and outcomes of different ethnicities in the US may inform treatment for hospitalized COVID-19 patients. Aim of this study is to identify predictors of mortality among US races/ethnicities. Design Setting and participants: We retrospectively analyzed de-identified data from 9,873 COVID-19 patients who were hospitalized at 15 US hospital centers in 11 states (March 2020-November 2020). Main Outcomes and Measures: The primary outcome was to identify predictors of mortality in hospitalized COVID-19 patients. Results: Among the 9,873 patients, there were 64.1% African Americans (AA), 19.8% Caucasians, 10.4% Hispanics, and 5.7% Asians, with 50.7% female. Males showed higher in-hospital mortality (20.9% vs. 15.3%, p=0.001). Non- survivors were significantly older (67 vs. 61 years) than survivors. Patients in New York had the highest in-hospital mortality (OR=3.54 (3.03 - 4.14)). AA patients possessed higher prevalence of comorbidities, had longer hospital stay, higher ICU admission rates, increased requirement for mechanical ventilation and higher in-hospital mortality compared to other races/ethnicities. Gastrointestinal symptoms (GI), particularly diarrhea, were more common among minority patients. Among GI symptoms and laboratory findings, abdominal pain (5.3%, p=0.03), elevated AST (n=2653, 50.2%, p=<0.001, OR=2.18), bilirubin (n=577, 12.9%, p=0.01) and low albumin levels (n=361, 19.1%, p=0.03) were associated with mortality. Multivariate analysis (adjusted for age, sex, race, geographic location) indicates that patients with asthma, COPD, cardiac disease, hypertension, diabetes mellitus, immunocompromised status, shortness of breath and cough possess higher odds of in-hospital mortality. Among laboratory parameters, patients with lymphocytopenia (OR2=2.50), lymphocytosis (OR2=1.41), and elevations of serum CRP (OR2=4.19), CPK (OR2=1.43), LDH (OR2=2.10), troponin (OR2=2.91), ferritin (OR2=1.88), AST (OR2=2.18), D-dimer (OR2=2.75) are more prone to death. Patients on glucocorticoids (OR2=1.49) and mechanical ventilation (OR2=9.78) have higher in-hospital mortality. Conclusion: These findings suggest that older age, male sex, AA race, and hospitalization in New York were associated with higher in-hospital mortality rates from COVID-19 in early pandemic stages. Other predictors of mortality included the presence of comorbidities, shortness of breath, cough elevated serum inflammatory markers, altered lymphocyte count, elevated AST, and low serum albumin. AA patients comprised a disproportionate share of COVID-19 death in the US during 2020 relative to other races/ethnicities.

Conceptual shifts needed to understand the dynamic interactions of genes, environment, epigenetics, social processes, and behavioral choices.

Social and behavioral research in public health is often intimately tied to profound, but frequently neglected, biological influences from underlying genetic, environmental, and epigenetic events. The dynamic interplay between the life, social, and behavioral sciences often remains underappreciated and underutilized in addressing complex diseases and disorders and in developing effective remediation strategies. Using a case-study format, we present examples as to how the inclusion of genetic, environmental, and epigenetic data can augment social and behavioral health research by expanding the parameters of such studies, adding specificity to phenotypic assessments, and providing additional internal control in comparative studies. We highlight the important roles of gene-environment interactions and epigenetics as sources of phenotypic change and as a bridge between the life and social and behavioral sciences in the development of robust interdisciplinary analyses.

Community-initiated genomics.

Ancient DNA is used to connect enslaved African Americans to modern descendants.

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.

Worldwide distribution of allelic variation at the progesterone receptor locus and the incidence of female reproductive cancers.

OBJECTIVES: Global patterns of the incidence of cancer are often attributed to environmental and lifestyle differences between regions. Less attention has been given to global patterns of allelic variation of genes that may contribute to the risk of developing cancer. METHODS: We genotyped samples from 21 populations for four variants of the progesterone receptor (PR) gene. One is an Alu insertion in intron 7 which defines the PROGINS haplotype. The others include a promoter region SNP 331+ G/A (rs10895068), a haplotype defining T/C substitution in intron 6 (rs561650), and an A/T substitution (rs608995) in the 3' untranslated region of the gene. All variants have been investigated elsewhere in association with female reproductive cancers in western populations. RESULTS: We found population differences in the frequency of each of these alleles across study populations (P < 0.01, log-likelihood G statistic, computed in FSTAT) and therefore examined the correlation between the frequency of each genetic variant and the incidence of three female reproductive cancers (breast, uterine, and ovarian) obtained from the Globocan 2008 database. Breast and ovarian cancer incidence were significantly correlated with the frequency of the Alu insertion (r = 0.86 and 0.53) and the +331 A variant (r = 0.57 and 0.73). CONCLUSIONS: Our data expand the information on genetic variation at the PR locus in non-western populations and support an argument for more work on the genetic epidemiology of cancer among nonwestern populations.

Discovery of rare variants implicated in schizophrenia using next-generation sequencing.

Schizophrenia is a highly heritable psychiatric disorder that affects 1% of the population. Genome-wide association studies have identified common variants in candidate genes associated with schizophrenia, but the genetics mechanisms of this disorder have not yet been elucidated. The discovery of rare genetic variants that contribute to schizophrenia symptoms promises to help explain the missing heritability of the disease. Next generation sequencing techniques are revolutionizing the field of psychiatric genetics. Various statistical approaches have been developed for rare variant association testing in case-control and family studies. Targeted resequencing, whole exome sequencing and whole genome sequencing combined with these computational tools are used for the discovery of rare genetic variations in schizophrenia. The findings provide useful information for characterizing the rare mutations and elucidating the genetic mechanisms by which the variants cause schizophrenia.

Including Vulnerable Populations in the Assessment of Data From Vulnerable Populations.

Data science has made great strides in harnessing the power of big data to improve human life across a broad spectrum of disciplines. Unfortunately this informational richesse is not equitably spread across human populations. Vulnerable populations remain both under-studied and under-consulted on the use of data derived from their communities. This lack of inclusion of vulnerable populations as data collectors, data analyzers and data beneficiaries significantly restrains the utility of big data applications that contribute to human well-ness. Here we present three case studies: (1) Describing a novel genomic dataset being developed with clinical and ethnographic insights in African Americans, (2) Demonstrating how a tutorial that enables data scientists from vulnerable populations to better understand criminal justice bias using the COMPAS dataset, and (3) investigating how Indigenous genomic diversity contributes to future biomedical interventions. These cases represent some of the outstanding challenges that big data science presents when addressing vulnerable populations as well as the innovative solutions that expanding science participation brings.

Identification of trace metals and potential anthropogenic influences on the historic New York African Burial Ground population: A pXRF technology approach.

The New York African Burial Ground (NYABG) is the country's oldest and largest burial site of free and enslaved Africans. Re-discovered in 1991, this site provided evidence of the biological and cultural existence of a 17th and 18th Century historic population viewing their skeletal remains. However, the skeletal remains were reburied in October 2003 and are unavailable for further investigation. The analysis of grave soil samples with modern technology allows for the assessment of trace metal presence. Portable X-ray fluorescence (pXRF) spectrometry provides a semi-quantitative and non-destructive method to identify trace metals of this population and in the surrounding environment. Sixty-five NYABG soil samples were analyzed on a handheld Bruker Tracer III- SD XRF with 40 kV of voltage and a 30µA current. Presence of As, Cu, and Zn can potentially decipher the influence of the local 18th Century pottery factories. Elevated levels of Sr validate the assumed heavy vegetative diets of poor and enslaved Africans of the time. Decreased levels of Ca may be due in part to the proximity of the Collect Pond, the existing water table until the early 19th Century, and Manhattan's rising sea level causing an elevated water table washing away the leached Ca from human remains. These data help us reconstruct the lives of these early Americans in what became New York City.

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.

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.