Population Genetic Inference from Personal Genome Data: Impact of Ancestry and Admixture on Human Genomic Variation

Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas—70% of the European ancestry in today’s African Americans dates back to European gene flow happening only 7–8 generations ago.     

History shaped the geographic distribution of genomic admixture on the island of Puerto Rico

Contemporary genetic variation among Latin Americans human groups reflects population migrations shaped by complex historical, social and economic factors. Consequently, admixture patterns may vary by geographic regions ranging from countries to neighborhoods. We examined the geographic variation of admixture across the island of Puerto Rico and the degree to which it could be explained by historic and social events. We analyzed a census-based sample of 642 Puerto Rican individuals that were genotyped for 93 ancestry informative markers (AIMs) to estimate African, European and Native American ancestry. Socioeconomic status (SES) data and geographic location were obtained for each individual. There was significant geographic variation of ancestry across the island. In particular, African ancestry demonstrated a decreasing East to West gradient that was partially explained by historical factors linked to the colonial sugar plantation system. SES also demonstrated a parallel decreasing cline from East to West. However, at a local level, SES and African ancestry were negatively correlated. European ancestry was strongly negatively correlated with African ancestry and therefore showed patterns complementary to African ancestry. By contrast, Native American ancestry showed little variation across the island and across individuals and appears to have played little social role historically. The observed geographic distributions of SES and genetic variation relate to historical social events and mating patterns, and have substantial implications for the design of studies in the recently admixed Puerto Rican population. More generally, our results demonstrate the importance of incorporating social and geographic data with genetics when studying contemporary admixed populations.     

Ancestral proportions and their association with skin pigmentation and bone mineral density in Puerto Rican women from New York city

Hispanic and African American populations exhibit an increased risk of obesity compared with populations of European origin, a feature that may be related to inherited risk alleles from Native American and West African parental populations. However, a relationship between West African ancestry and obesity-related traits, such as body mass index (BMI), fat mass (FM), and fat-free mass (FFM), and with bone mineral density (BMD) in African American women has only recently been reported. In order to evaluate further the influence of ancestry on body composition phenotypes, we studied a Hispanic population with substantial European, West African, and Native American admixture. We ascertained a sample of Puerto Rican women living in New York (n=64), for whom we measured BMI and body composition variables, such as FM, FFM, percent body fat, and BMD. Additionally, skin pigmentation was measured as the melanin index by reflectance spectroscopy. We genotyped 35 autosomal ancestry informative markers and estimated population and individual ancestral proportions in terms of European, West African, and Native American contributions to this population. The ancestry proportions corresponding to the three parental populations are: 53.3±2.8% European, 29.1±2.3% West African, and 17.6±2.4% Native American. We detected significant genetic structure in this population with a number of different tests. A highly significant correlation was found between skin pigmentation and individual ancestry (R²=0.597, P<0.001) that was not attributable to differences in socioeconomic status. A significant association was also found between BMD and European admixture (R²=0.065, P=0.042), but no such correlation was evident with BMI or the remaining body composition measurements. We discuss the implications of our findings for the potential use of this Hispanic population for admixture mapping.     

Admixture in Hispanics: distribution of ancestral population contributions in the Continental United States

The effect of gene flow on Hispanic populations from different geographic regions of the United States was analyzed using six autosomal DNA markers (LDLR, GYPA, HBGG, D7S8, GC, and HLA-DQA). By region of sampling, the Hispanic populations showed different ancestry contributions, from a trihybrid structure with European, Native American, and African contributions (California, Nevada, Florida, New Jersey, and Virginia) to a dihybrid structure with European and American contributions (Southwest population) or European and African contributions (Pennsylvania and Southeast population). These findings allowed us to define two regional groups, the West and the East. In the former, Native American contributions ranged from 35.58% to 57.87%; in the East region the values ranged from 0% to 21.27%. An African influence was similar in both regions, ranging from 0% to 17.11%, with a tendency of increasing in the East region. These data reflect the different origins of the Hispanic populations that led to the present ones. In the West, Hispanics are mostly of Mexican origin, and in the East, they are predominantly of Cuban and Puerto Rican origin.     

Reconstructing Native American Migrations from Whole-Genome and Whole-Exome Data

There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is in MXL, in CLM, and in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern America ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas thousand years ago (kya), supports that the MXL Ancestors split kya, with a subsequent split of the ancestors to CLM and PUR kya. The model also features effective populations of in Mexico, in Colombia, and in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations.     

Exploring the legacy of African and Indigenous Caribbean admixture in Puerto Rico

Objectives

From an anthropological genetic perspective, little is known about the ethnogenesis of African descendants in Puerto Rico. Furthermore, historical interactions between Indigenous Caribbean and African descendant peoples that may be reflected in the ancestry of contemporary populations are understudied. Given this dearth of genetic research and the precedence for Afro-Indigenous interactions documented by historical, archeological, and other lines of evidence, we sought to assess the biogeographic origins of African descendant Puerto Ricans and to query the potential for Indigenous ancestry within this community.

Materials and Methods

Saliva samples were collected from 58 self-identified African descendant Puerto Ricans residing in Puerto Rico. We sequenced whole mitochondrial genomes and genotyped Y chromosome haplogroups for each male individual (n = 25). Summary statistics, comparative analyses, and network analysis were used to assess diversity and variation in haplogroup distribution between the sample and comparative populations.

Results

As indicated by mitochondrial haplogroups, 66% had African, 5% had European, and 29% had Indigenous American matrilines. Along the Y chromosome, 52% had African, 28% had Western European, 16% had Eurasian, and, notably, 4% had Indigenous American patrilines. Both mitochondrial and Y chromosome haplogroup frequencies were significantly different from several comparative populations.

Discussion

Biogeographic origins are consistent with historical accounts of African, Indigenous American, and European ancestry. However, this first report of Indigenous American paternal ancestry in Puerto Rico suggests distinctive features within African descendant communities on the island. Future studies expanding sampling and incorporating higher resolution genetic markers are necessary to more fully understand African descendant history in Puerto Rico.     

Population admixture associated with disease prevalence in the Boston Puerto Rican health study

Older Puerto Ricans living in the continental U.S. suffer from higher rates of diabetes, obesity, cardiovascular disease and depression compared to non-Hispanic White populations. Complex diseases, such as these, are likely due to multiple, potentially interacting, genetic, environmental and social risk factors. Presumably, many of these environmental and genetic risk factors are contextual. We reasoned that racial background may modify some of these risk factors and be associated with health disparities among Puerto Ricans. The contemporary Puerto Rican population is genetically heterogeneous and originated from three ancestral populations: European settlers, native Taíno Indians, and West Africans. This rich-mixed ancestry of Puerto Ricans provides the intrinsic variability needed to untangle complex gene–environment interactions in disease susceptibility and severity. Herein, we determined whether a specific ancestral background was associated with either of four major disease outcomes (diabetes, obesity, cardiovascular disease, and depression). We estimated the genetic ancestry of 1,129 subjects from the Boston Puerto Rican Health Study based on genotypes of 100 ancestry informative markers (AIMs). We examined the effects of ancestry on tests of association between single AIMs and disease traits. The ancestral composition of this population was 57.2% European, 27.4% African, and 15.4% Native American. African ancestry was negatively associated with type 2 diabetes and cardiovascular disease, and positively correlated with hypertension. It is likely that the high prevalence rate of diabetes in Africans, Hispanics, and Native Americans is not due to genetic variation alone, but to the combined effects of genetic variation interacting with environmental and social factors. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Evaluating the X Chromosome-Specific Diversity of Colombian Populations Using Insertion/Deletion Polymorphisms

The European and African contribution to the pre-existing Native American background has influenced the complex genetic pool of Colombia. Because colonisation was not homogeneous in this country, current populations are, therefore, expected to have different proportions of Native American, European and African ancestral contributions. The aim of this work was to examine 11 urban admixed populations and a Native American group, called Pastos, for 32 X chromosome indel markers to expand the current knowledge concerning the genetic background of Colombia. The results revealed a highly diverse genetic background comprising all admixed populations, harbouring important X chromosome contributions from all continental source populations. In addition, Colombia is genetically sub-structured, with different proportions of European and African influxes depending on the regions. The samples from the North Pacific and Caribbean coasts have a high African ancestry, showing the highest levels of diversity. The sample from the South Andean region showed the lowest diversity and significantly higher proportion of Native American ancestry than the other samples from the North Pacific and Caribbean coasts, Central-West and Central-East Andean regions, and the Orinoquian region. The results of admixture analysis using X-chromosomal markers suggest that the high proportion of African ancestry in the North Pacific coast was primarily male driven. These men have joined to females with higher Native American and European ancestry (likely resulting from a classic colonial asymmetric mating type: European male x Amerindian female). This high proportion of male-mediated African contributions is atypical of colonial settings, suggesting that the admixture occurred during a period when African people were no longer enslaved. In the remaining regions, the African contribution was primarily female-mediated, whereas the European counterpart was primarily male driven and the Native American ancestry contribution was not gender biased.     

Self-reported ethnicity and genetic ancestry in relation to oral cancer and pre-cancer in Puerto Rico

Background

Hispanics are known to be an extremely diverse and genetically admixed ethnic group. The lack of methodologies to control for ethnicity and the unknown admixture in complex study populations of Hispanics has left a gap in understanding certain cancer disparity issues. Incidence rates for oral and pharyngeal cancer (OPC) in Puerto Rico are among the highest in the Western Hemisphere. We conducted an epidemiological study to examine risk and protective factors, in addition to possible genetic susceptibility components, for oral cancer and precancer in Puerto Rico.

Methodology/Principal Findings

We recruited 310 Puerto Rico residents who had been diagnosed with either an incident oral squamous cell carcinoma, oral precancer, or benign oral condition. Participants completed an in-person interview and contributed buccal cells for DNA extraction. ABI Biosystem Taqman™ primer sets were used for genotyping 12 ancestry informative markers (AIMs). Ancestral group estimates were generated using maximum likelihood estimation software (LEADMIX), and additional principal component analysis was carried out to detect population substructures. We used unconditional logistic regression to assess the contribution of ancestry to the risk of being diagnosed with either an oral cancer or precancer while controlling for other potential confounders. The maximum likelihood estimates showed that study participants had a group average ancestry contribution of 69.9% European, 24.5% African, and 5.7% detectable Native American. The African and Indigenous American group estimates were significantly higher than anticipated. Neither self-identified ethnicity nor ancestry markers showed any significant associations with oral cancer/precancer risk in our study.

Conclusions/Significance

The application of ancestry informative markers (AIMs), specifically designed for Hispanics, suggests no hidden population substructure is present based on our sampling and provides a viable approach for the evaluation and control of ancestry in future studies involving Hispanic populations.     

Characterizing the admixed African ancestry of African Americans

Background

Accurate, high-throughput genotyping allows the fine characterization of genetic ancestry. Here we applied recently developed statistical and computational techniques to the question of African ancestry in African Americans by using data on more than 450,000 single-nucleotide polymorphisms (SNPs) genotyped in 94 Africans of diverse geographic origins included in the HGDP, as well as 136 African Americans and 38 European Americans participating in the Atherosclerotic Disease Vascular Function and Genetic Epidemiology (ADVANCE) study. To focus on African ancestry, we reduced the data to include only those genotypes in each African American determined statistically to be African in origin.

Results

From cluster analysis, we found that all the African Americans are admixed in their African components of ancestry, with the majority contributions being from West and West-Central Africa, and only modest variation in these African-ancestry proportions among individuals. Furthermore, by principal components analysis, we found little evidence of genetic structure within the African component of ancestry in African Americans.

Conclusions

These results are consistent with historic mating patterns among African Americans that are largely uncorrelated to African ancestral origins, and they cast doubt on the general utility of mtDNA or Y-chromosome markers alone to delineate the full African ancestry of African Americans. Our results also indicate that the genetic architecture of African Americans is distinct from that of Africans, and that the greatest source of potential genetic stratification bias in case-control studies of African Americans derives from the proportion of European ancestry.     

Population stratification confounds genetic association studies among Latinos

In the United States, asthma prevalence and mortality are the highest among Puerto Ricans and the lowest among Mexicans. Case-control association studies are a powerful strategy for identifying genes of modest effect in complex diseases. However, studies of complex disorders in admixed populations such as Latinos may be confounded by population stratification. We used ancestry informative markers (AIMs) to identify and correct for population stratification among Mexican and Puerto Rican subjects participating in case-control studies of asthma. Three hundred and sixty-two subjects with asthma (Mexican: 181, Puerto Rican: 181) and 359 ethnically matched controls (Mexican: 181, Puerto Rican: 178) were genotyped for 44 AIMs. We observed a greater than expected degree of association between pairs of AIMs on different chromosomes in Mexicans (P < 0.00001) and Puerto Ricans (P < 0.00002) providing evidence for population substructure and/or recent admixture. To assess the effect of population stratification on association studies of asthma, we measured differences in genetic background of cases and controls by comparing allele frequencies of the 44 AIMs. Among Puerto Ricans but not in Mexicans, we observed a significant overall difference in allele frequencies between cases and controls (P = 0.0002); of 44 AIMs tested, 8 (18%) were significantly associated with asthma. However, after adjustment for individual ancestry, only two of these markers remained significantly associated with the disease. Our findings suggest that empirical assessment of the effects of stratification is critical to appropriately interpret the results of case-control studies in admixed populations.     

A genomewide admixture map for Latino populations

Admixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equal promise for Latinos, who typically inherit a mix of European, Native American, and African ancestry. However, admixture mapping in Latinos has not been practical because of the lack of a map of ancestry-informative markers validated in Native American and other populations. To address this, we screened multiple databases, containing millions of markers, to identify 4,186 markers that were putatively informative for determining the ancestry of chromosomal segments in Latino populations. We experimentally validated each of these markers in at least 232 new Latino, European, Native American, and African samples, and we selected a subset of 1,649 markers to form an admixture map. An advantage of our strategy is that we focused our map on markers distinguishing Native American from other ancestries and restricted it to markers with very similar frequencies in Europeans and Africans, which decreased the number of markers needed and minimized the possibility of false disease associations. We evaluated the effectiveness of our map for localizing disease genes in four Latino populations from both North and South America.     

Genomic Ancestry,Self-Rated Health and Its Association with Mortality in an Admixed Population: 10 Year Follow-Up of the Bambui-Epigen (Brazil) Cohort Study of Ageing

Background

Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification.

Materials/Methods

We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians. We also examined whether genomic ancestry and ethnoracial self-classification affect the predictive value of SRH for subsequent mortality.

Results

European ancestry predominated among participants, followed by African and Native American (median = 84.0%, 9.6% and 5.3%, respectively); the prevalence of Non-White (Mixed and Black) was 39.8%. Persons at higher levels of African and Native American genomic ancestry, and those self-identified as Non-White, were more likely to report poor health than other groups, even after controlling for socioeconomic conditions and an array of self-reported and objective physical health measures. Increased risks for mortality associated with worse SRH trajectories were strong and remarkably similar (hazard ratio ~3) across all genomic ancestry and ethno-racial groups.

Conclusions

Our results demonstrated for the first time that higher levels of African and Native American genomic ancestry—and the inverse for European ancestry—were strongly correlated with worse SRH in a Latin American admixed population. Both genomic ancestry and ethnoracial self-classification did not modify the strong association between baseline SRH or SRH trajectory, and subsequent mortality.     

Evaluation of Group Genetic Ancestry of Populations from Philadelphia and Dakar in the Context of Sex-Biased Admixture in the Americas

Background

Population history can be reflected in group genetic ancestry, where genomic variation captured by the mitochondrial DNA (mtDNA) and non-recombining portion of the Y chromosome (NRY) can separate female- and male-specific admixture processes. Genetic ancestry may influence genetic association studies due to differences in individual admixture within recently admixed populations like African Americans.

Principal Findings

We evaluated the genetic ancestry of Senegalese as well as European Americans and African Americans from Philadelphia. Senegalese mtDNA consisted of ∼12% U haplotypes (U6 and U5b1b haplotypes, common in North Africa) while the NRY haplotypes belonged solely to haplogroup E. In Philadelphia, we observed varying degrees of admixture. While African Americans have 9–10% mtDNAs and ∼31% NRYs of European origin, these results are not mirrored in the mtDNA/NRY pools of European Americans: they have less than 7% mtDNAs and less than 2% NRYs from non-European sources. Additionally, there is <2% Native American contribution to Philadelphian African American ancestry and the admixture from combined mtDNA/NRY estimates is consistent with the admixture derived from autosomal genetic data. To further dissect these estimates, we have analyzed our samples in the context of different demographic groups in the Americas.

Conclusions

We found that sex-biased admixture in African-derived populations is present throughout the Americas, with continual influence of European males, while Native American females contribute mainly to populations of the Caribbean and South America. The high non-European female contribution to the pool of European-derived populations is consistently characteristic of Iberian colonization. These data suggest that genomic data correlate well with historical records of colonization in the Americas.     

A genomewide admixture mapping panel for Hispanic/Latino populations

Admixture mapping (AM) is a promising method for the identification of genetic risk factors for complex traits and diseases showing prevalence differences among populations. Efficient application of this method requires the use of a genomewide panel of ancestry-informative markers (AIMs) to infer the population of origin of chromosomal regions in admixed individuals. Genomewide AM panels with markers showing high frequency differences between West African and European populations are already available for disease-gene discovery in African Americans. However, no such a map is yet available for Hispanic/Latino populations, which are the result of two-way admixture between Native American and European populations or of three-way admixture of Native American, European, and West African populations. Here, we report a genomewide AM panel with 2,120 AIMs showing high frequency differences between Native American and European populations. The average intermarker genetic distance is ~1.7 cM. The panel was identified by genotyping, with the Affymetrix GeneChip Human Mapping 500K array, a population sample with European ancestry, a Mesoamerican sample comprising Maya and Nahua from Mexico, and a South American sample comprising Aymara/Quechua from Bolivia and Quechua from Peru. The main criteria for marker selection were both high information content for Native American/European ancestry (measured as the standardized variance of the allele frequencies, also known as "f value") and small frequency differences between the Mesoamerican and South American samples. This genomewide AM panel will make it possible to apply AM approaches in many admixed populations throughout the Americas.     

Reconstructing the Population Genetic History of the Caribbean

The Caribbean basin is home to some of the most complex interactions in recent history among previously diverged human populations. Here, we investigate the population genetic history of this region by characterizing patterns of genome-wide variation among 330 individuals from three of the Greater Antilles (Cuba, Puerto Rico, Hispaniola), two mainland (Honduras, Colombia), and three Native South American (Yukpa, Bari, and Warao) populations. We combine these data with a unique database of genomic variation in over 3,000 individuals from diverse European, African, and Native American populations. We use local ancestry inference and tract length distributions to test different demographic scenarios for the pre- and post-colonial history of the region. We develop a novel ancestry-specific PCA (ASPCA) method to reconstruct the sub-continental origin of Native American, European, and African haplotypes from admixed genomes. We find that the most likely source of the indigenous ancestry in Caribbean islanders is a Native South American component shared among inland Amazonian tribes, Central America, and the Yucatan peninsula, suggesting extensive gene flow across the Caribbean in pre-Columbian times. We find evidence of two pulses of African migration. The first pulse—which today is reflected by shorter, older ancestry tracts—consists of a genetic component more similar to coastal West African regions involved in early stages of the trans-Atlantic slave trade. The second pulse—reflected by longer, younger tracts—is more similar to present-day West-Central African populations, supporting historical records of later transatlantic deportation. Surprisingly, we also identify a Latino-specific European component that has significantly diverged from its parental Iberian source populations, presumably as a result of small European founder population size. We demonstrate that the ancestral components in admixed genomes can be traced back to distinct sub-continental source populations with far greater resolution than previously thought, even when limited pre-Columbian Caribbean haplotypes have survived.     

Admixture analysis of a rural population of the state of Guerrero, Mexico

We studied 156 individuals of Native American descent from the city of Tlapa in the state of Guerrero in western Mexico. Most individuals' ethnicity was either Nahua, Mixtec, or Tlapanec, but self-identified Mestizos and individuals of mixed ethnicities were also included in the sample. We typed 24 autosomal, one Y-chromosome, and four mitochondrial ancestry-informative markers (AIMs) to estimate group and individual admixture proportions, and determine whether the admixture process involved directional gene flow between parental groups. When genetically defined (GD) Mestizos were excluded from the analysis, Native American ancestry represented approximately 98% of the population's gene pool, while European and West African ancestry represented approximately 1% each. Maternally inherited markers also showed an exceptionally high Native American contribution (98.5%), as did the paternally inherited marker, DYS199 (90.7%). We did not detect genetic structure in this population using these AIMs, which appears consistent with the homogeneity of the sample in terms of admixture proportions. The addition of GD Mestizos to the sample did not produce a considerable change in admixture estimates, but it had a major effect on population structure. These results show that the population of Tlapa in Guerrero, Mexico, has experienced little admixture with Europeans and/or West Africans. They also show that the impact of a small number of admixed individuals on an otherwise homogeneous population might have profound implications on subsequent ancestry/phenotype analysis and mapping strategies. We suggest that heterogeneity is a major characteristic of Mexican populations and, as a consequence, should not be disregarded when designing epidemiological studies of Mexican and Mexican American populations.     

Dissecting the within-Africa ancestry of populations of African descent in the Americas

Background

The ancestry of African-descended Americans is known to be drawn from three distinct populations: African, European, and Native American. While many studies consider this continental admixture, few account for the genetically distinct sources of ancestry within Africa – the continent with the highest genetic variation. Here, we dissect the within-Africa genetic ancestry of various populations of the Americas self-identified as having primarily African ancestry using uniparentally inherited mitochondrial DNA.

Methods and Principal Findings

We first confirmed that our results obtained using uniparentally-derived group admixture estimates are correlated with the average autosomal-derived individual admixture estimates (hence are relevant to genomic ancestry) by assessing continental admixture using both types of markers (mtDNA and Y-chromosome vs. ancestry informative markers). We then focused on the within-Africa maternal ancestry, mining our comprehensive database of published mtDNA variation (∼5800 individuals from 143 African populations) that helped us thoroughly dissect the African mtDNA pool. Using this well-defined African mtDNA variation, we quantified the relative contributions of maternal genetic ancestry from multiple W/WC/SW/SE (West to South East) African populations to the different pools of today''s African-descended Americans of North and South America and the Caribbean.

Conclusions

Our analysis revealed that both continental admixture and within-Africa admixture may be critical to achieving an adequate understanding of the ancestry of African-descended Americans. While continental ancestry reflects gender-specific admixture processes influenced by different socio-historical practices in the Americas, the within-Africa maternal ancestry reflects the diverse colonial histories of the slave trade. We have confirmed that there is a genetic thread connecting Africa and the Americas, where each colonial system supplied their colonies in the Americas with slaves from African colonies they controlled or that were available for them at the time. This historical connection is reflected in different relative contributions from populations of W/WC/SW/SE Africa to geographically distinct Africa-derived populations of the Americas, adding to the complexity of genomic ancestry in groups ostensibly united by the same demographic label.     

Comparing genetic ancestry and self-reported race/ethnicity in a multiethnic population in New York City

Self-reported race/ethnicity is frequently used in epidemiological studies to assess an individual’s background origin. However, in admixed populations such as Hispanic, self-reported race/ethnicity may not accurately represent them genetically because they are admixed with European, African and Native American ancestry. We estimated the proportions of genetic admixture in an ethnically diverse population of 396 mothers and 188 of their children with 35 ancestry informative markers (AIMs) using the STRUCTURE version 2.2 program. The majority of the markers showed significant deviation from Hardy-Weinberg equilibrium in our study population. In mothers self-identified as Black and White, the imputed ancestry proportions were 77.6% African and 75.1% European respectively, while the racial composition among self-identified Hispanics was 29.2% European, 26.0% African, and 44.8% Native American. We also investigated the utility of AIMs by showing the improved fitness of models in paraoxanase-1 genotype-phenotype associations after incorporating AIMs; however, the improvement was moderate at best. In summary, a minimal set of 35 AIMs is sufficient to detect population stratification and estimate the proportion of individual genetic admixture; however, the utility of these markers remains questionable.     

Association of serum lipid components and obesity with genetic ancestry in an admixed population of elderly women

The prevalence of metabolic disorders varies among ethnic populations and these disorders represent a critical health care issue for elderly women. This study investigated the correlation between genetic ancestry and body composition, metabolic traits and clinical status in a sample of elderly women. Clinical, nutritional and anthropometric data were collected from 176 volunteers. Genetic ancestry was estimated using 23 ancestry-informative markers. Pearsons correlation test was used to examine the relationship between continuous variables and an independent samples t-test was used to compare the means of continuous traits within categorical variables. Overall ancestry was a combination of European (57.49%), Native American (25.78%) and African (16.73%). Significant correlations were found for European ancestry with body mass index (r = 0.165; p = 0.037) and obesity (mean difference (MD) = 5.3%; p = 0.042). African ancestry showed a significant correlation with LDL (r = 0.159, p = 0.035), VLDL (r = −0.185; p = 0.014), hypertriglyceridemia (MD = 6.4%; p = 0.003) and hyperlipidemia (MD = 4.8%; p = 0.026). Amerindian ancestry showed a significant correlation with triglyceride levels (r = 0.150; p = 0.047) and hypertriglyceridemia (MD = 4.5%; p = 0.039). These findings suggest that genetic admixture may influence the etiology of lipid metabolism-related diseases and obesity in elderly women.