Genetic Ancestry Estimates Research Articles

Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis.

Background and ObjectiveHispanics with multiple sclerosis (MS) present younger and more often with optic neuritis (ON) as compared to Whites in the western United States. Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and ON and age at onset of MS in Hispanics.MethodsData were obtained for 1033 self‐identified Hispanics with MS from four MS‐based registries from four academic institutions across the United States January 2016–April 2017. Multivariate regression models, utilizing genetic ancestry estimates for Native American (NA), African, and European ancestry, were used to assess the relationship between genetic ancestry and ON presentation and age of MS onset, defined as age at first symptom.ResultsGenetic ancestry and ON proportions varied by region where NA ancestry and ON proportions were highest among Hispanics in the southwestern United States (40% vs. 19% overall for NA and 38% vs. 25% overall for ON). A strong inverse correlation was observed between NA and European ancestry (r = −0.83). ON presentation was associated with younger age of onset (OR: 0.98; 95% CI: 0.96–0.99; P = 7.80 × 10−03) and increased NA ancestry (OR: 2.35 for the highest versus the lowest quartile of NA ancestry; 95% CI: 1.35–4.10; P = 2.60 × 10−03). Younger age of onset was found to be associated with a higher proportion NA (Beta: −5.58; P = 3.49 × 10−02) and African ancestry (Beta: −10.07; P = 1.39 × 10−03).InterpretationEthnic differences associated with genetic admixture could influence clinical presentation in Hispanics with MS; underscoring the importance of considering genetic substructure in future clinical, genetic, and epigenetic studies in Hispanics.

Abstract C34: Association of genetic ancestry with colorectal tumor characteristics in Puerto Rican Hispanics

Abstract Background: Colorectal cancer (CRC) is the 1st cause of cancer deaths in Puerto Rican Hispanics (PRH). Even though PRH have a lower incidence of CRC, when compared to other ethnic groups, their mortality rates are higher. As the 2nd largest Hispanic population on the United States, the increased CRC mortality rates for this ethnic group have a large socio-economic burden. The CRC epidemiologic data supports the importance of studying this cancer as a health disparity in PRH. The genetic background of the Puerto Rican population, which is mix of European, African and Amerindian races, could account, at least in part, for the differences observed in the CRC mortality rates for this population. The objective of this project was to assess the role of genetic ancestry in CRC risk and clinicopathological features of CRC tumors in the PRH population. Methods: We used a panel of 105 ancestry informative markers (AIMs) to estimate genetic ancestry in 224 PRH CRC cases and 202 PRH controls. Additionally, we examined the association of genetic ancestry estimates with CRC risk and clinicopathological characteristics of CRC tumors in our study population using the Bayesian Markov Chain Monte Carlo method implemented in the software STRUCTURE. Logistic regression analysis was used to determine the association of genetic ancestry with disease risk. Pearson's Chi-Square and Fisher's Exact Test was used to determine the association of categorical values of genetic ancestry with tumor clinicopathological characteristics. Results: Our results showed that the genetic ancestry mean estimates for the PRH population were 60% for European, 21% for African and 19% for Amerindian. No association of genetic ancestry with CRC risk in the PRH population was found in our study (OR= 0.86 [0.43-1.69], p=0.655). However, genetic ancestry was found to have a significant role on the CRC tumor characteristics of the studied population. High African ancestry (>21.0%) was associated with distal tumor location, when compared to low African ancestry (≤ 21.0%) (p=0.012). Furthermore, low Amerindian ancestry (≤ 19.2%) was associated with poorly differentiated tumors (p= 0.022). Conclusion: The preliminary results presented in this study show that genetic ancestry is associated with tumor location and differentiation, both associated with CRC prognosis. Additional studies are needed to fully elucidate the role of genetic ancestry in CRC susceptibility and prognosis. Citation Format: Julyann Pérez-Mayoral, Marievelisse Soto, Maria González-Pons, Belisa Suárez, Myrta I. Olivera, Ebony Shah, Rick Kittles, Marcia R. Cruz-Correa. Association of genetic ancestry with colorectal tumor characteristics in Puerto Rican Hispanics. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C34.

Abstract B25: Impact of neighborhood obesogenic factors on obesity in over 100,000 participants of the Multiethnic Cohort Study

Abstract Introduction: The obesity epidemic is a serious health priority with important consequences on obesity-associated cancers. Socioeconomic (SES) and “obesogenic” attributes of neighborhoods may promote obesity by providing a context where it is difficult to engage in physical activity and/or access healthy foods. This may be particularly relevant for minority populations that have limited neighborhood resources and experience higher levels of obesity. However, the extent to which these neighborhood factors translate into individual levels of body mass index (BMI) have been mixed among racial/ethnic groups. Therefore, leveraging the scale and racial/ethnic diversity of the Multiethnic Cohort (MEC) study, we examined the associations between neighborhood obesogenic factors and BMI among African Americans, Japanese Americans, Latinos, and Whites in California. Methods: Study subjects included 107,697 MEC participants, ages 45-75, residing in California (93% from Los Angeles County) with geocoded addresses and data available on BMI at baseline questionnaire (1993-1996). Residential baseline addresses were geocoded to latitude and longitude coordinates and assigned to 1990 Census block groups to ascertain neighborhood levels of SES, population density, and commute patterns. In addition, geocodes were linked to business data to quantify neighborhood attributes of the retail/restaurant food environment, parks, recreational facilities, walkability, traffic density, and total businesses within a residential buffer area of one mile in radius. Polytomous logistic regression was conducted to examine the relationship between the obesogenic environment and BMI in kg/m2 (underweight: BMI<18.5; normal weight: BMI=18.5-<25 (reference); overweight BMI=25-<30; obese BMI>30) adjusting for age, sex, and race/ethnicity and including all neighborhood obesogenic factors. Stratified analyses were conducted by gender and race/ethnicity. Results: Lower neighborhood SES was significantly associated with higher odds of being overweight and obese. For males, in comparison to the highest SES quintile (Q5), the odds ratios and 95% confidence intervals for obesity with decreasing SES quintiles were Q4: OR=1.36 (95% CI: 1.20-1.50), Q3: OR=1.59; (95% CI: 1.40-1.81), Q2: OR=1.70 (95% CI: 1.49-1.93), and Q1: OR=1.89 (95% CI: 1.63-2.19). For females, similar patterns of associations were seen although larger associations were observed (Q4: OR=1.52 (95% CI: 1.36-1.70), Q3: OR=2.11 (95% CI: 1.89-2.34), Q2: OR=2.72 (95% CI: 2.43-3.03), Q1: OR=3.34 (95% CI: 2.94-3.78)). All racial/ethnic groups demonstrated similar patterns of associations between SES and obesity. Neighborhoods with smaller density of businesses (i.e. fewer nearby walkable destinations) were significantly associated with higher odds of obesity (ORQ1 vs. Q5=1.24; 95% CI: 1.14-1.34). This association was consistently observed among African American males and females, U.S. born Latino males, foreign-born Latino females, and White females. For White males and females, residence in neighborhoods with lower levels of commuting by car or motorcycle were associated with lower odds of obesity in comparison to residence in neighborhoods at the highest level of commuting by car or motorcycle (males ORQ1 vs. Q5=0.51; 95% CI: 0.35-0.76; females ORQ1 vs. Q5=0.64; 95% CI: 0.48-0.84). Conclusion: These findings demonstrate the impact of the neighborhood environment on obesity with complex relationships observed across gender and racial/ethnic groups. Future analyses will incorporate individual-level health behaviors such as dietary factors, physical activity and smoking, as well estimates of genetic ancestry. Our understanding of this relationship between the obesogenic environment and obesity provides a framework for future studies of neighborhood obesogenic factors and cancer risk. Citation Format: Iona Cheng, Juan Yang, Andrew Hertz, Christina Clarke, Cheryl Albright, Loic Le Marchand, Laurence Kolonel, Brian Henderson, Kristine Monroe, Scarlett Lin-Gomez, Lynne Wilkens. Impact of neighborhood obesogenic factors on obesity in over 100,000 participants of the Multiethnic Cohort Study. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B25.

Evaluating the role of admixture in cancer therapy via in vitro drug response and multivariate genome-wide associations.

We investigate the role of ethnicity and admixture in drug response across a broad group of chemotherapeutic drugs. Also, we generate hypotheses on the genetic variants driving differential drug response through multivariate genome-wide association studies. Immortalized lymphoblastoid cell lines from 589 individuals (Hispanic or non-Hispanic/Caucasian) were used to investigate dose-response for 28 chemotherapeutic compounds. Univariate and multivariate statistical models were used to elucidate associations between genetic variants and differential drug response as well as the role of ethnicity in drug potency and efficacy. For many drugs, the variability in drug response appears to correlate with self-reported race and estimates of genetic ancestry. Additionally, multivariate genome-wide association analyses offered interesting hypotheses governing these differential responses.

Case Study on Ancestry Estimation in an Alaskan Native Family: Identity and Safeguards Against Reductionism.

Understanding the complexities of ancestry-related identity is a necessary component of ethically sound research related to the genetic ancestry of modern-day communities. This is especially true when working with indigenous populations, given the legal and social implications that genetic ancestry interpretations may have in these communities. This study employs a multicomponent approach to explore the intricacies of ancestry-related identity within one extended family with members who identify as Alaskan Native. The seven participants were interviewed about their own self-identity, perceptions regarding genetic ancestry estimation, and their knowledge of oral family history. Additionally, each participant consented to having his or her genetic ancestry estimated. The researchers also surveyed ancestry-related documents, such as census records, birth certificates, and Certificates of Indian Blood. These three different perspectives-oral family history and self-identity, genetic ancestry estimation, historical and legal documentation-illustrate the complex nature of ancestry-related identity within the context of indigenous and colonial interactions in North America. While estimates of genetic ancestry broadly reflected each individual's self-reported biogeographic ancestry and supported all described and historically reported biological relationships, the estimates did not always match federally recorded blood quantum values, nor did they provide any information on relationships at the tribe or clan level. Employing a multicomponent approach and engaging study participants may help to safeguard against genetic essentialism and provide a more nuanced understanding of ancestry-related identity within a larger political, legal, and historical context.

Pro-inflammatory cytokines correlate with classical risk factors for atherosclerosis in the admixed Brazilian older women

AimMeasurement of inflammatory markers for risk stratification of vascular disorders has been the focus of numerous investigations worldwide, and usually reveals augmented levels of circulating cytokines/chemokines among carriers of classic risk factors for atherosclerosis. Nonetheless, this low-grade inflammatory milieu detected in aged individuals tends to be influenced by body composition. Moreover, cardiovascular risk factors have a complex genetic etiology, and disregarding the genetic heritage may produce spurious results owing to interethnic differences. In this complex scenario, our study was designed to verify the existence and strength of the association between selected mediators of systemic inflammation and classic risk factors of cardiovascular diseases (CVD). MethodsIn a sample of post-menopausal older women, correlation analyses explored the association of circulating levels of IL1α, IL1β, IL8, IL10 and IL12 with atherosclerosis-related clinical/metabolic parameters, using age, body mass index (BMI), genetic ancestry estimates as standard correction factors. Further adjustment for use of therapeutic agents was applied when appropriate. ResultsOur analyses revealed association of log10-transformed IL-12 titers with VLDL-c levels (r=.192; p=.002) and with SBP (r−.185; p=.003), and of log10-transformed IL-8 titers with GLY (r=.235; p<.001). ConclusionInterpretation to the results account to a possible dysregulation of the PPAR signaling pathway to explain the association of IL12 and VLDL-c, and to IL8-driven mechanisms to promote dysglycemia. No previous report sought to investigate the relationship between this set of inflammatory markers and classic risk factors for atherosclerosis correcting for the heterogeneity in genetic admixture and body composition of Brazilian post-menopausal women.

Analyses of genetic ancestry enable key insights for molecular ecology

Gene flow and recombination in admixed populations produce genomes that are mosaic combinations of chromosome segments inherited from different source populations, that is, chromosome segments with different genetic ancestries. The statistical problem of estimating genetic ancestry from DNA sequence data has been widely studied, and analyses of genetic ancestry have facilitated research in molecular ecology and ecological genetics. In this review, we describe and compare different model-based statistical methods used to infer genetic ancestry. We describe the conceptual and mathematical structure of these models and highlight some of their key differences and shared features. We then discuss recent empirical studies that use estimates of genetic ancestry to analyse population histories, the nature and genetic basis of species boundaries, and the genetic architecture of traits. These diverse studies demonstrate the breadth of applications that rely on genetic ancestry estimates and typify the genomics-enabled research that is becoming increasingly common in molecular ecology. We conclude by identifying key research areas where future studies might further advance this field.

Cytokine Gene Polymorphisms and Alzheimer's Disease in Brazil

Background: Single-nucleotide polymorphisms in genes encoding immunological mediators can affect the biological activity of these molecules by regulating transcription, translation, or secretion, modulating the genetic risk of inflammatory damage in Alzheimer's disease (AD). Nonetheless, the Brazilian contingent is highly admixed, and few association trials performed herein with AD patients have considered genetic ancestry estimates as co-variables when investigating markers for this complex trait. Methods: We analyzed polymorphisms in 10 inflammatory genes and compared the genotype distribution across outpatients with late-onset AD and noncognitively impaired subjects from Midwest Brazil under a strict criterion, and controlling for ancestry heritage and ApoE genotype. Results: Our findings show an almost 40% lower chance of AD (p = 0.004) among homozygotes of the IL10 -1082A allele (rs1800896). Dichotomization to ApoE and mean ancestry levels did not affect protection, except among those with greater European or minor African heritage. Conclusion: The IL10 locus seems to affect the onset of AD in a context sensitive to the genetic ancestry of Brazilian older adults.

Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study

Idiopathic pulmonary fibrosis (IPF) is a devastating disease that probably involves several genetic loci. Several rare genetic variants and one common single nucleotide polymorphism (SNP) of MUC5B have been associated with the disease. Our aim was to identify additional common variants associated with susceptibility and ultimately mortality in IPF. First, we did a three-stage genome-wide association study (GWAS): stage one was a discovery GWAS; and stages two and three were independent case-control studies. DNA samples from European-American patients with IPF meeting standard criteria were obtained from several US centres for each stage. Data for European-American control individuals for stage one were gathered from the database of genotypes and phenotypes; additional control individuals were recruited at the University of Pittsburgh to increase the number. For controls in stages two and three, we gathered data for additional sex-matched European-American control individuals who had been recruited in another study. DNA samples from patients and from control individuals were genotyped to identify SNPs associated with IPF. SNPs identified in stage one were carried forward to stage two, and those that achieved genome-wide significance (p<5 × 10(-8)) in a meta-analysis were carried forward to stage three. Three case series with follow-up data were selected from stages one and two of the GWAS using samples with follow-up data. Mortality analyses were done in these case series to assess the SNPs associated with IPF that had achieved genome-wide significance in the meta-analysis of stages one and two. Finally, we obtained gene-expression profiling data for lungs of patients with IPF from the Lung Genomics Research Consortium and analysed correlation with SNP genotypes. In stage one of the GWAS (542 patients with IPF, 542 control individuals matched one-by-one to cases by genetic ancestry estimates), we identified 20 loci. Six SNPs reached genome-wide significance in stage two (544 patients, 687 control individuals): three TOLLIP SNPs (rs111521887, rs5743894, rs5743890) and one MUC5B SNP (rs35705950) at 11p15.5; one MDGA2 SNP (rs7144383) at 14q21.3; and one SPPL2C SNP (rs17690703) at 17q21.31. Stage three (324 patients, 702 control individuals) confirmed the associations for all these SNPs, except for rs7144383. Linkage disequilibrium between the MUC5B SNP (rs35705950) and TOLLIP SNPs (rs111521887 [r(2)=0·07], rs5743894 [r(2)=0·16], and rs5743890 [r(2)=0·01]) was low. 683 patients from the GWAS were included in the mortality analysis. Individuals who developed IPF despite having the protective TOLLIP minor allele of rs5743890 carried an increased mortality risk (meta-analysis with fixed-effect model: hazard ratio 1·72 [95% CI 1·24-2·38]; p=0·0012). TOLLIP expression was decreased by 20% in individuals carrying the minor allele of rs5743890 (p=0·097), 40% in those with the minor allele of rs111521887 (p=3·0 × 10(-4)), and 50% in those with the minor allele of rs5743894 (p=2·93 × 10(-5)) compared with homozygous carriers of common alleles for these SNPs. Novel variants in TOLLIP and SPPL2C are associated with IPF susceptibility. One novel variant of TOLLIP, rs5743890, is also associated with mortality. These associations and the reduced expression of TOLLIP in patients with IPF who carry TOLLIP SNPs emphasise the importance of this gene in the disease. National Institutes of Health; National Heart, Lung, and Blood Institute; Pulmonary Fibrosis Foundation; Coalition for Pulmonary Fibrosis; and Instituto de Salud Carlos III.

Heterogeneity in Genetic Admixture across Different Regions of Argentina

The population of Argentina is the result of the intermixing between several groups, including Indigenous American, European and African populations. Despite the commonly held idea that the population of Argentina is of mostly European origin, multiple studies have shown that this process of admixture had an impact in the entire Argentine population. In the present study we characterized the distribution of Indigenous American, European and African ancestry among individuals from different regions of Argentina and evaluated the level of discrepancy between self-reported grandparental origin and genetic ancestry estimates. A set of 99 autosomal ancestry informative markers (AIMs) was genotyped in a sample of 441 Argentine individuals to estimate genetic ancestry. We used non-parametric tests to evaluate statistical significance. The average ancestry for the Argentine sample overall was 65% European (95%CI: 63–68%), 31% Indigenous American (28–33%) and 4% African (3–4%). We observed statistically significant differences in European ancestry across Argentine regions [Buenos Aires province (BA) 76%, 95%CI: 73–79%; Northeast (NEA) 54%, 95%CI: 49–58%; Northwest (NWA) 33%, 95%CI: 21–41%; South 54%, 95%CI: 49–59%; p<0.0001] as well as between the capital and immediate suburbs of Buenos Aires city compared to more distant suburbs [80% (95%CI: 75–86%) versus 68% (95%CI: 58–77%), p = 0.01]. European ancestry among individuals that declared all grandparents born in Europe was 91% (95%CI: 88–94%) compared to 54% (95%CI: 51–57%) among those with no European grandparents (p<0.001). Our results demonstrate the range of variation in genetic ancestry among Argentine individuals from different regions in the country, highlighting the importance of taking this variation into account in genetic association and admixture mapping studies in this population.

Abstract A67: IL-16 variants associated with prostate cancer risk in African Americans

Abstract Background: Prostate cancer (Pca) is the most common type of cancer among men in the United States, and its disproportionate incidence and mortality rates among ethnic groups are likely due to a combination of genes and environmental factors. While genome-wide association studies (GWASs) of European descents have identified candidate loci associated with Pca risk, including rs4072111 located in IL-16, the replication studies in African Americans (AAs) have been inconsistent, and GWASs have not yet produced many findings to resolve Pca health disparities. IL-16 is over-expressed in tumor cells possibly mediating expression of other cytokines that promote tumor growth. Here we explore SNP variation in IL-16 in AAs and test for association with Pca in AAs. Method: Two hundred and seventy-seven (277) tagging SNPs spanning IL-16 (79.20Mb to 79.45Mb on chromosome 15) were genotyped in 496 AA Pca cases and 501 controls from Washington, DC. In order to replicate our findings, 11 of the SNPs were also typed in additional 400 AA Pca cases and controls from Chicago, IL. One hundred (100) unlinked ancestry informative markers were also typed for each sample. West African genetic ancestry estimates were obtained using STRUCTURE. We tested for allelic association and calculated odds ratios using logistic regression, adjusting for West African ancestry and age. Empiric p-values were obtained by adaptive permutation. Results: Our first stage analyses revealed that a cluster of 20 IL-16 SNPs were significantly associated with Pca risk. The strongest association was found at rs7175701 (P=1.2 × 10−8), which lies within intron 26 of IL-16. In the replication population, two SNPs, slightly linked to rs7175701, but within the 3′UTR region were also strongly associated with Pca risk (P&amp;lt;0.005). Our study provides evidence that IL-16 polymorphisms likely play a role to Pca susceptibility in AAs. Many of the significantly associated SNPs are linked to rs11325 which is a candidate SNP for a miRNA target region in IL-16. Although the exact mechanism is unclear, additional functional studies are warranted. Impact: Our findings are significant given that there has been limited focus on the role of IL-16 genetic polymorphisms on Pca risk in AAs. Understanding the role of cytokines such as IL-16 in tumor growth in diverse populations is important, and could likely lead to the development of useful biomarkers for cancer screening and/or potential therapeutics. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A67.

North African Influences and Potential Bias in Case-Control Association Studies in the Spanish Population

BackgroundDespite the limited genetic heterogeneity of Spanish populations, substantial evidences support that historical African influences have not affected them uniformly. Accounting for such population differences might be essential to reduce spurious results in association studies of genetic factors with disease. Using ancestry informative markers (AIMs), we aimed to measure the African influences in Spanish populations and to explore whether these might introduce statistical bias in population-based association studies.Methodology/Principal FindingsWe genotyped 93 AIMs in Spanish (from the Canary Islands and the Iberian Peninsula) and Northwest Africans, and conducted population and individual-based clustering analyses along with reference data from the HapMap, HGDP-CEPH, and other sources. We found significant differences for the Northwest African influence among Spanish populations from as low as ≈5% in Spanish from the Iberian Peninsula to as much as ≈17% in Canary Islanders, whereas the sub-Saharan African influence was negligible. Strikingly, the Northwest African ancestry showed a wide inter-individual variation in Canary Islanders ranging from 0% to 96%, reflecting the violent way the Islands were conquered and colonized by the Spanish in the XV century. As a consequence, a comparison of allele frequencies between Spanish samples from the Iberian Peninsula and the Canary Islands evidenced an excess of markers with significant differences. However, the inflation of p-values for the differences was adequately controlled by correcting for genetic ancestry estimates derived from a reduced number of AIMs.Conclusions/SignificanceAlthough the African influences estimated might be biased due to marker ascertainment, these results confirm that Northwest African genetic footprints are recognizable nowadays in the Spanish populations, particularly in Canary Islanders, and that the uneven African influences existing in these populations might increase the risk for false positives in association studies. Adjusting for population stratification assessed with a few dozen AIMs would be sufficient to control this effect.

Population analysis of vitamin D receptor polymorphisms and the role of genetic ancestry in an admixed population

The vitamin D receptor (VDR) is an essential protein related to bone metabolism. Some VDR alleles are differentially distributed among ethnic populations and display variable patterns of linkage disequilibrium (LD). In this study, 200 unrelated Brazilians were genotyped using 21 VDR single nucleotide polymorphisms (SNPs) and 28 ancestry informative markers. The patterns of LD and haplotype distribution were compared among Brazilian and the HapMap populations of African (YRI), European (CEU) and Asian (JPT+CHB) origins. Conditional regression and haplotype-specific analysis were performed using estimates of individual genetic ancestry in Brazilians as a quantitative trait. Similar patterns of LD were observed in the 5′ and 3′ gene regions. However, the frequency distribution of haplotype blocks varied among populations. Conditional regression analysis identified haplotypes associated with European and Amerindian ancestry, but not with the proportion of African ancestry. Individual ancestry estimates were associated with VDR haplotypes. These findings reinforce the need to correct for population stratification when performing genetic association studies in admixed populations.

Efficient Population Assignment and Outlier Detection in Human Populations Using Biallelic Markers Chosen by Principal Component–Based Rankings

Whole-genome studies of genetic variation are now performed routinely and have accelerated the identification of disease-associated allelic variants, positive selection, recombination, and structural variation. However, these studies are sensitive to the presence of outlier data from individuals of different ancestry than the rest of the sample. Currently, the most common method of excluding outlier individuals is to collect a population sample and exclude outliers after genome-wide data have been collected. Here we show that a small collection of 20-27 polymorphic Alu insertions, selected using a principal component-based method with genetic ancestry estimates, may be used to easily assign Africans, East Asians, and Europeans to their population of origin. In addition, we show that samples from a geographically and genetically intermediate population (in our study, samples from India) can be identified within the original sample of Africans, East Asians, and Europeans. Finally, we show that outlier individuals from neighboring geographic regions (in our study, Yemen and sub-Saharan Africa) can be identified. These results will be of value in preselection of samples for more in-depth analysis as well as customized identification of maximally informative polymorphic markers for regional studies.

Recent advances of genetic ancestry testing in biomedical research and direct to consumer testing

In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between genetic ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real genetic risks. The latter point will become increasingly sensitive as several 'for profit companies' are offering ancestry and genetic testing directly to consumers and the consequences of the spread of the services of these companies are still unforeseeable.

Comparison of Statistical Methods for Estimating Genetic Admixture in a Lung Cancer Study of African Americans and Latinos

A variety of methods are available for estimating genetic admixture proportions in populations; however, few investigators have conducted detailed comparisons using empirical data. The authors characterized admixture proportions among self-identified African Americans (n = 535) and Latinos (n = 412) living in the San Francisco Bay Area who participated in a lung cancer case-control study (1998-2003). Individual estimates of genetic ancestry based on 184 informative markers were obtained from a Bayesian approach and 2 maximum likelihood approaches and were compared using descriptive statistics, Pearson correlation coefficients, and Bland-Altman plots. Case-control differences in individual admixture proportions were assessed using 2-sample t tests and logistic regression analysis. Results indicated that Bayesian and frequentist approaches to estimating admixture provide similar estimates and inferences. No difference was observed in admixture proportions between African-American cases and controls, but Latino cases and controls significantly differed according to Amerindian and European genetic ancestry. Differences in admixture proportions between Latino cases and controls were not unexpected, since cases were more likely to have been born in the United States. Genetic admixture proportions provide a quantitative measure of ancestry differences among Latinos that can be used in analyses of genetic risk factors.