Exploring the role of cancer fatalism and engagement with skin cancer genetic information in diverse primary care patients.

OBJECTIVE: To broaden the currently limited reach of genomic innovations, research is needed to understand how psychosocial and cultural factors influence reactions to genetic testing in diverse subgroups. Cancer fatalism is important in cancer prevention and deserves theoretical and empirical attention in the context of genomics and behavior change. METHODS: The current study employed data from a randomized controlled trial (N = 593) offering skin cancer genetic testing (using the melanocortin-1 receptor [MC1R] gene) in primary care in Albuquerque, New Mexico, USA. We examined interrelations of cancer fatalism with demographics, general health beliefs, perceived risk, perceived control, sun protection and skin screening behaviors and cancer worry in the skin cancer context stratified across Hispanic versus non-Hispanic ethnicity, and examined cancer fatalism as a moderator of intervention effects on study primary outcomes, including 3-month sun protection, cancer worry and perceived risk. RESULTS: Cancer fatalism was significantly related to the perception of control over skin cancer risk behaviors (ps ≤ 0.01) and demographics (ethnicity, education, health literacy; ps < 0.05), but not consistently related to general health beliefs or risk perception. Cancer fatalism did not moderate intervention effects on primary outcomes, except those with higher cancer fatalism randomized to intervention had higher levels of 3-month cancer worry (p = 0.019). CONCLUSIONS: These findings will guide future work considering the role of cancer fatalism in use of genomic technologies in the general population. This work anticipates strategies required to address cancer fatalism as translational genomics becomes more commonly available to diverse general population subgroups.

Beyond Serial Founder Effects: The Impact of Admixture and Localized Gene Flow on Patterns of Regional Genetic Diversity.

Geneticists have argued that the linear decay in within-population genetic diversity with increasing geographic distance from East Africa is best explained by a phylogenetic process of repeated founder effects, growth, and isolation. However, this serial founder effect (SFE) process has not yet been adequately vetted against other evolutionary processes that may also affect geospatial patterns of diversity. Additionally, studies of the SFE process have been largely based on a limited 52-population sample. In this modestly updated article, originally published in Human Biology in 2016 (vol. 88, no. 3, pp. 219-231), we assess the effects of founder effect, admixture, and localized gene flow processes on patterns of global and regional diversity using a published data set of 645 autosomal microsatellite genotypes from 5,415 individuals in 248 widespread populations. We used a formal tree-fitting approach to explore the role of founder effects. The approach involved fitting global and regional population trees to extant patterns of gene diversity and then systematically examining the deviations in fit. We also informally tested the SFE process using linear models of gene diversity versus waypoint geographic distances from Africa. We tested the role of localized gene flow using partial Mantel correlograms of gene diversity versus geographic distance controlling for the confounding effects of treelike genetic structure. We corroborate previous findings that global patterns of diversity, both within and between populations, are the product of an out-of-Africa SFE process. Within regions, however, diversity within populations is uncorrelated with geographic distance from Africa. Here, patterns of diversity have been largely shaped by recent interregional admixture and secondary range expansions. Our detailed analyses of the pattern of diversity within and between populations reveal that the signatures of different evolutionary processes dominate at different geographic scales. These findings have important implications for recent publications on the biology of race. Our new foreword situates these findings in a long line of anthropological research that categorically rejects racial interpretations of analyses of human diversity.

Colonialism, ethnogenesis, and biogeographic ancestry in the US Southwest.

OBJECTIVE: Differences between self-perceived biogeographic ancestry and estimates derived from DNA are potentially informative about the formation of ethnic identities in different sociohistorical contexts. Here, we compared self-estimates and DNA-estimates in New Mexico, where notions of shared ancestry and ethnic identity have been shaped by centuries of migration and admixture. MATERIALS AND METHODS: We asked 507 New Mexicans of Spanish-speaking descent (NMS) to list their ethnic identity and to estimate their percentages of European and Native American ancestry. We then compared self-estimates to estimates derived from 291,917 single nucleotide polymorphisms (SNPs), and we examined how differences between the estimates varied by ethnic identity. RESULTS: Most NMS (94%) predicted that they had non-zero percentages of European and Native American ancestry. Self-estimates and SNP-estimates were positively correlated (rEuropean  = 0.38, rNative-American  = 0.36, p < 0.001). The correlations belie systematic patterns of underestimation and overestimation based on ethnic identity. NMS with ancestral ties to 20th century immigrants, who identified as Mexican or Mexican American, often underestimated their European ancestry (self-estimate < SNP-estimate) and overestimated their Native American ancestry. The pattern was reversed for NMS who emphasized deep connections to colonial New Mexico and identified as Spanish or Spanish American. DISCUSSION: While NMS accurately predicted that they had European and Native American ancestry, they predicted ancestry percentages with only moderate accuracy. Differences between self-estimated and SNP-estimated ancestry were associated with ethnic identities that were shaped by migration to the region over the past 400 years. We connect ethnic identities and patterns of ancestry estimation to resistance to colonial hegemony and discuss the implications of our results for the construction of ethnic identities, now and in the past.

"Let's Talk about Skin Cancer": Examining Association between Family Communication about Skin Cancer, Perceived Risk, and Sun Protection Behaviors.

Family communication about skin cancer risk may motivate protective behaviors. However, it is unclear how widespread such communication might be. In this study, we describe prevalence and patterns (across environmental, personal, and behavioral factors) of family communication about skin cancer across N = 600 diverse (79% female, 48% Hispanic, 44% non-Hispanic White) primary care patients from Albuquerque, New Mexico, a geographical location with year-round sun exposure. Over half reported discussing general cancer (77%) and skin cancer risks (66%) with their families. The most frequent target of skin cancer risk communication included doctors (54%), followed by friends/coworkers (49%), spouse/partner (43%), other family members (38%), sisters (36%), mothers (36%), daughters (33%), sons (32%), father (24%), and brothers (22%). On average, participants reported having talked to three family members about skin cancer risks. The most frequently discussed content of skin cancer risk communication was the use of sun protection (89%), followed by the personal risk of skin cancer (68%), who had skin cancer in the family (60%), family risk of skin cancer (59%), time of sun exposure (57%), and skin cancer screening (57%). A family or personal history of cancer, higher perceived risk, higher health literacy, being non-Hispanic, having higher education or income, and proactive sun protective behavior were associated with greater family communication about general cancer and skin cancer risks. These study findings have implications for interventions that encourage discussions about skin cancer risk, sun protection, and skin cancer screening that lead to adoption of sun-safe behaviors.

Colonialism and the co-evolution of ethnic and genetic structure in New Mexico.

OBJECTIVE: Socially constructed ethnic identities are frequently rooted in beliefs about common descent that form when people with disparate cultures, languages, and biology come into contact. This study explores connections between beliefs about common descent, as represented by ethnic nomenclatures, and histories of migration and isolation ascertained from genomic data in New Mexicans of Spanish-speaking descent (NMS). MATERIALS AND METHODS: We interviewed 507 NMS who further identified using one of seven ethnic terms that they associated with beliefs about connections to past ancestors. For groups of individuals who identified using each term, we estimated biogeographic ancestry, fit admixture models to ancestry distributions, and partitioned genetic distance into admixture and drift components. RESULTS: Regardless of which ethnic term they used, all NMS had appreciable Native American (avg. 27%) and European ancestry (avg.71%). However, individuals who identified using terms associated with beliefs connecting them to colonial-period Spanish ancestors had significantly higher European ancestry than individuals who identified using terms associated with ancestral connections to post-colonial-period migrants from Mexico. Model-fitting analyses show that this ancestry difference reflects post-colonial gene flow with non-NMS European Americans, not colonial-period gene flow with Spaniards. Drift, not admixture, accounted for most of the genetic distance between NMS who expressed connections to Mexican versus Spanish ancestors, reflecting relative isolation of New Mexico and Mexico through the 19th century. DISCUSSION: Patterns of genomic diversity in NMS are consistent with beliefs about common descent in showing that New Mexico was isolated for generations following initial colonization. They are inconsistent with these beliefs in showing that all NMS have substantial European and Native American ancestry, and in showing that a proportion of European ancestry derives from post-colonial-period admixture with non-NMS European Americans. Our findings provide insights into the construction of ethnic identity in contexts of migration and isolation in New Mexico and, potentially, throughout human prehistory.

Social Identity in New Mexicans of Spanish-Speaking Descent Highlights Limitations of Using Standardized Ethnic Terminology in Research.

In this study, we evaluated the extent to which regional history has shaped the social identity nomenclature in New Mexicans of Spanish-speaking descent (NMSD). We asked 507 NMSD to list the social-identity terms they used to describe themselves and their parents, and we examined the correspondence between these choices and family ties to the region, birthplace, and continental ancestry. NMSD frequently identified using the regional terms "Nuevomexicano/a" (15%) and "Spanish" (12%). These individuals reported family ties to the region that predate New Mexican statehood. They and their parents were frequently born in New Mexico, frequently chose the other of the two terms as a secondary descriptor, and frequently ascribed one of the two terms to their parents. About 10% of NMSD identified as "Mexican American" and "Mexican." About 25% of these individuals, and more than half of their parents, were born in Mexico. They also frequently chose the other of the two terms as a secondary descriptor and frequently ascribed one of the two terms to their parents. Compared to NMSD who identified as "Mexican" and "Mexican American," individuals who identified as "Nuevomexicano/a" and "Spanish" had higher European ancestry and lower Native American and African ancestry. Our results also suggest that the term "Hispanic," frequently chosen as both a primary and secondary social identity term by NMSD, may, as it continues to rise in prominence, mask more deeply rooted and potential socially relevant aspects of social identity in New Mexico. More broadly, these results indicate that regional history influences social identity nomenclatures in ways that are potentially incompatible with US Office of Management and Budget standards. This incompatibility may adversely affect the ability of researchers in the social sciences to assess the causes of social inequality and health disparities in individuals of Spanish-speaking descent in different regions of the United States. We argue that future studies would benefit from more fine-grained, region-specific analyses of social identity.

Beyond Serial Founder Effects: The Impact of Admixture and Localized Gene Flow on Patterns of Regional Genetic Diversity.

Geneticists have argued that the linear decay in within-population genetic diversity with increasing geographic distance from East Africa is best explained by a phylogenetic process of repeated founder effects, growth, and isolation. However, this serial founder effect (SFE) process has not yet been adequately vetted against other evolutionary processes that may also affect geospatial patterns of diversity. Additionally, studies of the SFE process have been largely based on a limited 52-population sample. Here, we assess the effects of founder effect, admixture, and localized gene flow processes on patterns of global and regional diversity using a published data set of 645 autosomal microsatellite genotypes from 5,415 individuals in 248 widespread populations. We used a formal tree-fitting approach to explore the role of founder effects. The approach involved fitting global and regional population trees to extant patterns of gene diversity and then systematically examining the deviations in fit. We also informally tested the SFE process using linear models of gene diversity versus waypoint geographic distances from Africa. We tested the role of localized gene flow using partial Mantel correlograms of gene diversity versus geographic distance controlling for the confounding effects of treelike genetic structure. We corroborate previous findings that global patterns of diversity, both within and between populations, are the product of an out-of-Africa SFE process. Within regions, however, diversity within populations is uncorrelated with geographic distance from Africa. Here, patterns of diversity have been largely shaped by recent interregional admixture and secondary range expansions. Our detailed analyses of the pattern of diversity within and between populations reveal that the signatures of different evolutionary processes dominate at different geographic scales. These findings have important implications for recent publications on the biology of race.

The apportionment of human diversity revisited.

OBJECTIVES: Studies of the apportionment of human genetic diversity have found that local populations harbor nearly as much diversity as the species as a whole. These studies have been a valuable cornerstone in rejecting race as a biological framework in anthropology. The current study presents new analyses that use updated statistical methods based on bifurcating trees to assess the structure of human genetic diversity and its implications for the existence of canonical biological races. MATERIALS AND METHODS: We examine patterns of both goodness-of-fit and lack-of-fit of two bifurcating trees to patterns of diversity determined from autosomal short tandem repeat genotypes in 1,037 people representing 52 populations with worldwide distribution. RESULTS: From goodness-of-fit, we infer a root for the tree within Africa, and we recapitulate a pattern of decreasing genetic diversity with increasing geographic distance from Africa. From lack-of-fit, we present tentative evidence for admixture events with archaic hominins. We do not find evidence that long-range migration or local gene flow have contributed appreciably to the lack of fit at a global scale. CONCLUSION: This is the first study to find a root for a tree of human populations without comparison to a nonhuman out-group, and it is one of the first studies to identify a signature of admixture with archaic hominins without reference to ancient DNA. Our findings complement previous studies of the apportionment of human diversity and provide a more solid evolutionary foundation for the rejection of biological race. Am J Phys Anthropol 160:561-569, 2016. © 2015 Wiley Periodicals, Inc.

Error and bias in race and ethnicity descriptions in medical examiner records in New Mexico: Consequences for understanding mortality among Hispanic/Latinos.

Researchers use public records from deceased individuals to identify trends in manners and causes of death. Errors in the description of race and ethnicity can affect the inferences researchers draw, adversely impacting public health policies designed to eliminate health inequity. Using the New Mexico Decedent Image Database, we examine: 1) the accuracy of death investigator descriptions of race and ethnicity by comparing their reports to those from next of kin (NOK), 2) the impact of decedent age and sex on disagreement between death investigators and NOK, and 3) the relationship between investigators' descriptions of decedent race and ethnicity and cause and manner of death from forensic pathologists (n = 1813). Results demonstrate that investigators frequently describe race and ethnicity incorrectly for Hispanic/Latino decedents, especially regarding homicide manner of death and injury and substance abuse causes of death. Inaccuracies may cause biased misperceptions of violence within specific communities and affect investigative processes.

Rejection of a serial founder effects model of genetic and linguistic coevolution.

Recent genetic studies attribute the negative correlation between population genetic diversity and distance from Africa to a serial founder effects (SFE) evolutionary process. A recent linguistic study concluded that a similar decay in phoneme inventories in human languages was also the product of the SFE process. However, the SFE process makes additional predictions for patterns of neutral genetic diversity, both within and between groups, that have not yet been tested on phonemic data. In this study, we describe these predictions and test them on linguistic and genetic samples. The linguistic sample consists of 725 widespread languages, which together contain 908 distinct phonemes. The genetic sample consists of 614 autosomal microsatellite loci in 100 widespread populations. All aspects of the genetic pattern are consistent with the predictions of SFE. In contrast, most of the predictions of SFE are violated for the phonemic data. We show that phoneme inventories provide information about recent contacts between languages. However, because phonemes change rapidly, they cannot provide information about more ancient evolutionary processes.

Effect of Superstitious Beliefs and Risk Intuitions on Genetic Test Decisions.

INTRODUCTION: Moving beyond numeric representations of risk perceptions, we examine cognitive causation, or superstitious thinking, and negative affect in risk as predictors of MC1R (i.e., moderate v. high risk) skin cancer genetic testing and responses to this testing. METHODS: Participants (N = 496) completed baseline assessments using validated measures of cognitive causation (beliefs that thinking about cancer risk increases cancer likelihood) and negative affect in risk (negative feelings generated during risk perception) and subsequently received a test offer. Participants could access a website to learn about and request genetic testing. Those who tested (n = 167) completed assessments of cognitive and affective reactions 2 wk after testing, including the Impact of Events-Revised Intrusive thoughts subscale. RESULTS: Those with higher negative affect in risk were less likely to return a saliva sample for testing (odds ratio = 0.98, 95% confidence interval = 0.96-0.99). Those with higher cognitive causation reported more fear (b = 0.28-0.31; P's < 0.05). Higher negative affect in risk was associated with more emotion-laden test responses, particularly in those receiving higher-risk as compared with average-risk results. CONCLUSION: Negative affect in risk did not hamper test information seeking, although it did inhibit the uptake of genetic testing. Those with higher cognitive causation showed more fear regarding their test result, as indicated by higher distress in those who received average-risk results and lower believability in those who received higher-risk results.

Comprehension of skin cancer genetic risk feedback in primary care patients.

Few studies have examined comprehension and miscomprehension of genetic risk feedback for moderate-risk genes in the general population. We examined the prevalence and nature of accurate and inaccurate genetic risk feedback comprehension among those who received genetic testing for melanocortin-1-receptor (MC1R) gene variants that confer moderate melanoma risk. Participants (N = 145 Albuquerque, NM) were tested as part of a randomized controlled trial. Two weeks after receiving MC1R genetic risk feedback, participants answered open-ended questions regarding their reactions to the MC1R feedback report. Participants' comprehension of their feedback (average-risk or higher-risk for melanoma) was evaluated through qualitative analysis of open-ended responses. Most participants demonstrated comprehension of their feedback results (i.e., 63% of average-risk participants [ARPs]; 51% of higher-risk participants [HRPs]). Miscomprehension was evident in fewer participants (i.e., 16% of ARPs, 11% of HRPs). A few ARPs misunderstood the purpose of testing, whereas a few HRPs reported confusion about the meaning of their risk feedback. Some participants' responses to the open-ended questions were too ambiguous to ascertain comprehension or miscomprehension (i.e., 21% of ARPs, 38% of HRPs). Taken together, these findings suggest that genetic testing feedback for MC1R risk variants is largely comprehensible to general population participants. This study adds to the work examining comprehension and usage of common, moderate risk genetic information in public health contexts. However, to maximize the utility of genetic risk information in the general population, further research is needed to investigate and address areas where common genetic risk feedback misunderstandings occur.

The impact of founder effects, gene flow, and European admixture on native American genetic diversity.

Recent studies have concluded that the global pattern of neutral genetic diversity in humans reflects a series of founder effects and population movements associated with our recent expansion out of Africa. In contrast, regional studies tend to emphasize the significance of more complex patterns of colonization, gene flow, and secondary population movements in shaping patterns of diversity. Our objective in this study is to examine how founder effects, gene flow, and European admixture have molded patterns of neutral genetic diversity in the Americas. Our strategy is to test the fit of a serial founder effects process to the pattern of neutral autosomal genetic variation and to examine the contribution of gene flow and European admixture to departures from fit. The genetic data consist of 678 autosomal microsatellite loci assayed by Wang and colleagues in 530 individuals in 29 widely distributed Native American populations. We find that previous evidence for serial founder effects in the Americas may be driven in part by high levels of European admixture in northern North America, intermediate levels in Central America, and low levels in eastern South America. Geographically patterned admixture may also account for previously reported genetic differences between Andean and Amazonian groups. Though admixture has obscured the precise details of precontact evolutionary processes, we find that genetic diversity is still largely hierarchically structured and that gene flow between neighboring groups has had surprisingly little impact on macrogeographic patterns of genetic diversity in the Americas.

Genetic and linguistic coevolution in Northern Island Melanesia.

Recent studies have detailed a remarkable degree of genetic and linguistic diversity in Northern Island Melanesia. Here we utilize that diversity to examine two models of genetic and linguistic coevolution. The first model predicts that genetic and linguistic correspondences formed following population splits and isolation at the time of early range expansions into the region. The second is analogous to the genetic model of isolation by distance, and it predicts that genetic and linguistic correspondences formed through continuing genetic and linguistic exchange between neighboring populations. We tested the predictions of the two models by comparing observed and simulated patterns of genetic variation, genetic and linguistic trees, and matrices of genetic, linguistic, and geographic distances. The data consist of 751 autosomal microsatellites and 108 structural linguistic features collected from 33 Northern Island Melanesian populations. The results of the tests indicate that linguistic and genetic exchange have erased any evidence of a splitting and isolation process that might have occurred early in the settlement history of the region. The correlation patterns are also inconsistent with the predictions of the isolation by distance coevolutionary process in the larger Northern Island Melanesian region, but there is strong evidence for the process in the rugged interior of the largest island in the region (New Britain). There we found some of the strongest recorded correlations between genetic, linguistic, and geographic distances. We also found that, throughout the region, linguistic features have generally been less likely to diffuse across population boundaries than genes. The results from our study, based on exceptionally fine-grained data, show that local genetic and linguistic exchange are likely to obscure evidence of the early history of a region, and that language barriers do not particularly hinder genetic exchange. In contrast, global patterns may emphasize more ancient demographic events, including population splits associated with the early colonization of major world regions.

Refined, regionally-specific data standards reveal heterogeneity in Hispanic death records.

Hispanic ethnicity can be captured with differing levels of granularity using various data standards, including those from the Office of Management and Budget, Health and Human Services and National Academy of Medicine. Previous research identified seven subgroups of Hispanics in New Mexico using open-ended interviews and information about the culture/history of the state. We examined age and manner of death to determine whether differences among subgroups are hidden by less-refined categorization. Significant differences in the mean age at death were found between some groups, including Spanish and Mexican Americans. We found an association between specific manners of death codes and subgroups. However, significance disappeared when manners of death were grouped (e.g. accident, homicide, etc.). This indicates that while certain manners of death are associated with group membership, overall types of death are not. Data descriptors for Hispanics should reflect more refined, regionally relevant groups, in order to unmask heterogeneity.

Childhood dietary quality predicts adult facial fluctuating asymmetry in contemporary New Mexicans.

Fluctuating asymmetry (FA) in adults is thought to reflect specific types of developmental stress. If true, adult FA may be a proxy for developmental stress in past as well as current populations. To date, studies of the link between development and adult FA have produced ambiguous results due to insufficient measurement data for childhood environments. This study seeks to overcome this limitation using a structural equation modeling approach to evaluate the relationship between 29 measures of developmental environments and precise measures of adult FA. Sociodemographic information and 3D facial photographs were collected from 80 adult New Mexicans. Facial FA was measured from the photographs using geometric morphometric analysis of 12 facial landmarks. Each participant responded to a questionnaire addressing the developmental environment, including childhood home environment, family SES, health, and dietary quality. We used structural equation models to examine predictive relationships between latent variables constructed from questionnaire responses and adult facial FA. Childhood dietary quality was negatively associated with adult FA scores, meaning that poorer diets predict higher FA (standardized path coefficient -0.174, p = 0.039). Factors that loaded positively on the dietary quality construct were a diet quality index, the frequency of homemade meals, and the frequency of homemade breakfast, while the frequency of fast-food meals loaded negatively. No other latent variable predicted adult facial FA. We posit that the negative relationship between dietary quality and FA reflects a negative energy balance experienced during development. Insufficient nutrition results in a reduced capacity to buffer against environmental perturbations, with increased FA as evidence. Given previously established links between FA and adult health outcomes in humans, this finding also underscores the importance of dietary quality during development for ensuring health and wellbeing later in life. These results indicate that FA in facial shape may signal the relative quality of dietary conditions during development.

Behavioral and Psychological Outcomes Associated with Skin Cancer Genetic Testing in Albuquerque Primary Care.

Public availability of genetic information is increasing; thus, efforts to improve diversity in basic and translational research in genomics is a top priority. Given the increasing U.S. incidence and mortality of melanoma, and the prevalence of common melanocortin-1 receptor (MC1R) gene melanoma risk variants in the general population, we examined genomic testing of MC1R for skin cancer risk in a randomized controlled trial in Albuquerque, New Mexico primary care. Participants were 48% Hispanic and were randomized 5:1 to a MC1R test invitation or usual care. We assessed 3 month sun protection, skin cancer screening, and skin cancer worry outcomes associated with testing, and key effect moderators (e.g., cancer risk perceptions, and skin cancer risk factors). Our findings indicate that the primary outcomes were unchanged by the MC1R test offer, test acceptance, and level of risk feedback. Moderator analyses showed that those with lower risk perception, and those with skin that readily tans, significantly increased their sun protection in response to higher than average risk feedback. Risk feedback did not prompt cancer worry, and average risk feedback did not erode existing sun protection. This study paves the way for the development of tailored strategies to address low skin cancer risk awareness in this understudied context of public health genomics.

Effects of health literacy skills, educational attainment, and level of melanoma risk on responses to personalized genomic testing.

OBJECTIVE: Few studies have examined how health literacy impacts responses to genetic information. METHODS: We examined this issue among 145 English or Spanish-speaking adult primary care patients enrolled in a trial that offered testing for MC1R gene variants that confer moderately increased melanoma risk. We investigated whether health literacy skills, educational attainment, or melanoma risk were related to short-term cognitive and affective responses to genetic test results. RESULTS: On average, participants found the test results to be highly believable and clear, with low levels of negative emotional responses and moderate levels of positive responses. In adjusted models, health literacy skills were significantly inversely associated with confusion (OR = 0.75, 95 % CI = 0.58, 0.96); those with higher education thought significantly less about their test results (ß = -0.66), were less hopeful (ß = -0.89), and had lower distress (ß = -1.15). We also observed a significant interaction (p < .001) between health literacy and melanoma risk in affecting the frequency of thoughts about test results. CONCLUSION: The findings indicate that health literacy skills may affect to what extent individuals elaborate cognitively on genetic information. PRACTICE IMPLICATIONS: Patients with lower health literacy skills or education may need support in understanding genetic test results.

The global pattern of gene identity variation reveals a history of long-range migrations, bottlenecks, and local mate exchange: implications for biological race.

Several recent studies have argued that human genetic variation conforms to a model of isolation by distance, whereas others see a predominant role for long-range migrations and bottlenecks. It is unclear whether either of these views fully describes the global pattern of human genetic variation. In this article, we use a coalescent-based simulation approach to compare the pattern of neutral genetic variation predicted by these views to the observed pattern estimated from neutral autosomal microsatellites assayed in 1,032 individuals from 53 globally-distributed populations. We find that neither view predicts every aspect of the observed pattern of variation on its own, but that a combination of the two does. Specifically, we demonstrate that the observed pattern of global gene identity variation is consistent with a history of serial population fissions, bottlenecks and long-range migrations associated with the peopling of major geographic regions, and gene flow between local populations. This history has produced a nested pattern of genetic structure that is inconsistent with the existence of independently evolving biological races. We consider the implications of our findings for methods that apportion variation into within- and between-group components and for medical genetics.