scholarly journals The Effects of Migration and Assortative Mating on Admixture Linkage Disequilibrium

2016 ◽  
Author(s):  
Noah Zaitlen ◽  
Scott Huntsman ◽  
Donglei Hu ◽  
Melissa Spear ◽  
Celeste Eng ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
African Americans ◽  
Assortative Mating ◽  
Random Mating ◽  
Historical Narrative ◽  
Model Complexity ◽  
Human Populations ◽  
Local Ancestry ◽  
Admixed Population ◽  
Demographic Inference

1AbstractStatistical models in medical and population genetics typically assume that individuals assort randomly in a population. While this simplifies model complexity, it contradicts an increasing body of evidence of non-random mating in human populations. Specifically, it has been shown that assortative mating is significantly affected by genomic ancestry. In this work we examine the effects of ancestry-assortative mating on the linkage disequilibrium between local ancestry tracks of individuals in an admixed population. To accomplish this, we develop an extension to the Wright-Fisher model that allows for ancestry based assortative mating. We show that ancestry-assortment perturbs the distribution of local ancestry linkage disequilibrium (LAD) and the variance of ancestry in a population as a function of the number of generations since admixture. This assortment effect can induce errors in demographic inference of admixed populations when methods assume random mating. We derive closed form formulae for LAD under an assortative-mating model with and without migration. We observe that LAD depends on the correlation of global ancestry of couples in each generation, the migration rate of each of the ancestral populations, the initial proportions of ancestral populations, and the number of generations since admixture. We also present the first evidence of ancestry-assortment in African Americans and examine LAD in simulated and real admixed population data of African Americans. We find that demographic inference under the assumption of random mating significantly underestimates the number of generations since admixture, and that accounting for assortative mating using the patterns of LAD results in estimates that more closely agrees with the historical narrative.

scholarly journals Putting RFMix and ADMIXTURE to the test in a complex admixed population

2020 ◽  
Author(s):  
Caitlin Uren ◽  
Eileen G. Hoal ◽  
Marlo Möller
Keyword(s):  
World Wide ◽  
Association Studies ◽  
Structured Populations ◽  
Human Populations ◽  
Computational Tools ◽  
Association Analyses ◽  
Local Ancestry ◽  
Diverse World ◽  
Admixed Population ◽  
Global And Local

Abstract Background Global and local ancestry inference in admixed human populations can be performed using computational tools implementing distinct algorithms. The development and resulting accuracy of these tools has been tested largely on populations with relatively straightforward admixture histories but little is known about how well they perform in more complex admixture scenarios. Results Using simulations, we show that RFMix outperforms ADMIXTURE in determining global ancestry proportions even in a complex 5-way admixed population, in addition to assigning local ancestry with an accuracy of 89%. The ability of RFMix to determine global and local ancestry to a high degree of accuracy, particularly in admixed populations provides the opportunity for more accurate association analyses. Conclusion This study highlights the utility of the extension of computational tools to become more compatible to genetically structured populations, as well as the need to expand the sampling of diverse world-wide populations. This is particularly noteworthy as modern-day societies are becoming increasingly genetically complex and some genetic tools and commonly used ancestral populations are less appropriate. Based on these caveats and the results presented here, we suggest that RFMix be used for both global and local ancestry estimation in world-wide complex admixture scenarios particularly when including these estimates in association studies.

scholarly journals Quantifying the prevalence of assortative mating in a human population

2019 ◽  
Author(s):  
Klaus Jaffe
Keyword(s):  
Assortative Mating ◽  
Genetic Relatedness ◽  
Random Mating ◽  
Human Populations ◽  
Genetic Composition ◽  
Genetic Studies ◽  
Maintenance Of Sex ◽  
Animal Populations ◽  
The Uk ◽  
First Time

AbstractFor the first time, empirical evidence allowed to construct the frequency distribution of a genetic relatedness index between the parents of about half a million individuals living in the UK. The results suggest that over 30% of the population is the product of parents mating assortatively. The rest is probably the offspring of parents matching the genetic composition of their partners randomly. High degrees of genetic relatedness between parents, i.e. extreme inbreeding, was rare. This result shows that assortative mating is likely to be highly prevalent in human populations. Thus, assuming only random mating among humans, as widely done in ecology and population genetic studies, is not an appropriate approximation to reality. The existence of assortative mating has to be accounted for. The results suggest the conclusion that both, assortative and random mating, are evolutionary stable strategies. This improved insight allows to better understand complex evolutionary phenomena, such as the emergence and maintenance of sex, the speed of adaptation, runaway adaptation, maintenance of cooperation, and many others in human and animal populations.

scholarly journals Putting RFMix and ADMIXTURE to the test in a complex admixed population

2019 ◽  
Author(s):  
Caitlin Uren ◽  
Eileen G. Hoal ◽  
Marlo Möller
Keyword(s):  
Association Studies ◽  
Structured Populations ◽  
Human Populations ◽  
Computational Tools ◽  
Local Ancestry ◽  
Population Structure Analysis ◽  
Admixed Population ◽  
Ancestry Inference ◽  
Global And Local ◽  
Local Ancestry Inference

AbstractGlobal and local ancestry inference in admixed human populations can be performed using computational tools implementing distinct algorithms, such as RFMix and ADMIXTURE. The accuracy of these tools has been tested largely on populations with relatively straightforward admixture histories but little is known about how well they perform in more complex admixture scenarios. Using simulations, we show that RFMix outperforms ADMIXTURE in determining global ancestry proportions in a complex 5-way admixed population. In addition, RFMix correctly assigns local ancestry with an accuracy of 89%. The increase in reported local ancestry inference accuracy in this population (as compared to previous studies) can largely be attributed to the recent availability of large-scale genotyping data for more representative reference populations. The ability of RFMix to determine global and local ancestry to a high degree of accuracy, allows for more reliable population structure analysis, scans for natural selection, admixture mapping and case-control association studies. This study highlights the utility of the extension of computational tools to become more relevant to genetically structured populations, as seen with RFMix. This is particularly noteworthy as modern-day societies are becoming increasingly genetically complex and some genetic tools are therefore less appropriate. We therefore suggest that RFMix be used for both global and local ancestry estimation in complex admixture scenarios.

scholarly journals Putting RFMix and ADMIXTURE to the test in a complex admixed population

2020 ◽  
Author(s):  
Caitlin Uren ◽  
Eileen G. Hoal ◽  
Marlo Möller
Keyword(s):  
World Wide ◽  
Association Studies ◽  
Structured Populations ◽  
Human Populations ◽  
Computational Tools ◽  
Association Analyses ◽  
Local Ancestry ◽  
Diverse World ◽  
Admixed Population ◽  
Global And Local

Abstract Background Global and local ancestry inference in admixed human populations can be performed using computational tools implementing distinct algorithms. The development and resulting accuracy of these tools has been tested largely on populations with relatively straightforward admixture histories but little is known about how well they perform in more complex admixture scenarios. Results Using simulations, we show that RFMix outperforms ADMIXTURE in determining global ancestry proportions even in a complex 5-way admixed population, in addition to assigning local ancestry with an accuracy of 89%. RFMix’s ability to determine global and local ancestry to a high degree of accuracy, particularly in admixed populations provides the opportunity for more accurate association analyses. Conclusion This study highlights the utility of the extension of computational tools to become more compatible to genetically structured populations, as well as the need to expand the sampling of diverse world-wide populations. This is particularly noteworthy as modern-day societies are becoming increasingly genetically complex and some genetic tools and commonly used ancestral populations are less appropriate. Based on these caveats and the results presented here, we suggest that RFMix be used for both global and local ancestry estimation in world-wide complex admixture scenarios particularly when including these estimates in association studies.

scholarly journals Putting RFMix and ADMIXTURE to the test in a complex admixed population

2020 ◽  
Author(s):  
Caitlin Uren ◽  
Eileen G. Hoal ◽  
Marlo Möller
Keyword(s):  
World Wide ◽  
Association Studies ◽  
Structured Populations ◽  
Human Populations ◽  
Computational Tools ◽  
Association Analyses ◽  
Local Ancestry ◽  
Diverse World ◽  
Admixed Population ◽  
Global And Local

Abstract Background Global and local ancestry inference in admixed human populations can be performed using computational tools implementing distinct algorithms. The development and resulting accuracy of these tools has been tested largely on populations with relatively straightforward admixture histories but little is known about how well they perform in more complex admixture scenarios. Results Using simulations, we show that RFMix outperforms ADMIXTURE in determining global ancestry proportions even in a complex 5-way admixed population, in addition to assigning local ancestry with an accuracy of 89%. The ability of RFMix to determine global and local ancestry to a high degree of accuracy, particularly in admixed populations provides the opportunity for more accurate association analyses. Conclusion This study highlights the utility of the extension of computational tools to become more compatible to genetically structured populations, as well as the need to expand the sampling of diverse world-wide populations. This is particularly noteworthy as modern-day societies are becoming increasingly genetically complex and some genetic tools and commonly used ancestral populations are less appropriate. Based on these caveats and the results presented here, we suggest that RFMix be used for both global and local ancestry estimation in world-wide complex admixture scenarios particularly when including these estimates in association studies.

scholarly journals Putting RFMix and ADMIXTURE to the test in a complex admixed population

2019 ◽  
Author(s):  
Caitlin Uren ◽  
Eileen G. Hoal ◽  
Marlo Möller
Keyword(s):  
World Wide ◽  
Association Studies ◽  
Structured Populations ◽  
Human Populations ◽  
Computational Tools ◽  
Association Analyses ◽  
Local Ancestry ◽  
Diverse World ◽  
Admixed Population ◽  
Global And Local

Abstract Background Global and local ancestry inference in admixed human populations can be performed using computational tools implementing distinct algorithms. The development and resulting accuracy of these tools has been tested largely on populations with relatively straightforward admixture histories but little is known about how well they perform in more complex admixture scenarios. Results Using simulations, we show that RFMix outperforms ADMIXTURE in determining global ancestry proportions even in a complex 5-way admixed population, in addition to assigning local ancestry with an accuracy of 89%. RFMix’s ability to determine global and local ancestry to a high degree of accuracy, particularly in admixed populations provides the opportunity for more accurate association analyses. Conclusion This study highlights the utility of the extension of computational tools to become more compatible to genetically structured populations, as well as the need to expand the sampling of diverse world-wide populations. This is particularly noteworthy as modern-day societies are becoming increasingly genetically complex and some genetic tools and commonly used ancestral populations are less appropriate. Based on these caveats and the results presented here, we suggest that RFMix be used for both global and local ancestry estimation in world-wide complex admixture scenarios particularly when including these estimates in association studies.

scholarly journals Detecting Heterogeneity in Population Structure Across the Genome in Admixed Populations

2015 ◽  
Author(s):  
Caitlin McHugh ◽  
Timothy A Thornton ◽  
Lisa Brown
Keyword(s):  
Population Structure ◽  
Native American ◽  
Native Americans ◽  
Random Mating ◽  
Phase Iii ◽  
European Ancestry ◽  
Human Populations ◽  
Genotype Data ◽  
Local Ancestry ◽  
Genomic Regions

The genetic structure of human populations is often characterized by aggregating measures of ancestry across the autosomal chromosomes. While it may be reasonable to assume that population structure patterns are similar genome-wide in relatively homogeneous populations, this assumption may not be appropriate for admixed populations, such as Hispanics and African Americans, with recent ancestry from two or more continents. Recent studies have suggested that systematic ancestry differences can arise at genomic locations in admixed populations as a result of selection and non-random mating. Here, we propose a method, which we refer to as the chromosomal ancestry differences (CAnD) test, for detecting heterogeneity in population structure across the genome. CAnD uses local ancestry inferred from SNP genotype data to identify chromosomes harboring genomic regions with ancestry contributions that are significantly different than expected. In simulation studies with real genotype data from Phase III of the HapMap Project, we demonstrate the validity and power of CAnD. We apply CAnD to the HapMap Mexican American (MXL) and African American (ASW) population samples; in this analysis the software RFMix is used to infer local ancestry at genomic regions assuming admixing from Europeans, West Africans, and Native Americans. The CAnD test provides strong evidence of heterogeneity in population structure across the genome in the MXL sample ($p=4e-05$), which is largely driven by elevated Native American ancestry and deficit of European ancestry on the X chromosomes. Among the ASW, all chromosomes are largely African derived and no heterogeneity in population structure is detected in this sample.

scholarly journals Assortative mating and the dynamical decoupling of genetic admixture levels from phenotypes that differ between source populations

2019 ◽  
Author(s):  
Jaehee Kim ◽  
Michael D. Edge ◽  
Amy Goldberg ◽  
Noah A. Rosenberg
Keyword(s):  
Assortative Mating ◽  
Genetic Architecture ◽  
Genetic Ancestry ◽  
Genetic Admixture ◽  
Human Populations ◽  
Source Population ◽  
Specific Source ◽  
Admixed Population ◽  
Source Populations ◽  
Over Time

AbstractSource populations for an admixed population can possess distinct patterns of genotype and pheno-type at the beginning of the admixture process. Such differences are sometimes taken to serve as markers of ancestry—that is, phenotypes that are initially associated with the ancestral background in one source population are taken to reflect ancestry in that population. Examples exist, however, in which genotypes or phenotypes initially associated with ancestry in one source population have decoupled from overall admixture levels, so that they no longer serve as proxies for genetic ancestry. We develop a mechanistic model for describing the joint dynamics of admixture levels and phenotype distributions in an admixed population. The approach includes a quantitative-genetic model that relates a phenotype to underlying loci that affect its trait value. We consider three forms of mating. First, individuals might assort in a manner that is independent of the overall genetic admixture level. Second, individuals might assort by a quantitative phenotype that is initially correlated with the genetic admixture level. Third, individuals might assort by the genetic admixture level itself. Under the model, we explore the relationship between genetic admixture level and phenotype over time, studying the effect on this relationship of the genetic architecture of the phenotype. We find that the decoupling of genetic ancestry and phenotype can occur surprisingly quickly, especially if the phenotype is driven by a small number of loci. We also find that positive assortative mating attenuates the process of dissociation in relation to a scenario in which mating is random with respect to genetic admixture and with respect to phenotype. The mechanistic framework suggests that in an admixed population, a trait that initially differed between source populations might be a reliable proxy for ancestry for only a short time, especially if the trait is determined by relatively few loci. The results are potentially relevant in admixed human populations, in which phenotypes that have a perceived correlation with ancestry might have social significance as ancestry markers, despite declining correlations with ancestry over time.Author SummaryAdmixed populations are populations that descend from two or more populations that had been separated for a long time at the beginning of the admixture process. The source populations typically possess distinct patterns of genotype and phenotype. Hence, early in the admixture process, phenotypes of admixed individuals can provide information about the extent to which these individuals possess ancestry in a specific source population. To study correlations between admixture levels and phenotypes that differ between source populations, we construct a genetic and phenotypic model of the dynamical process of admixture. Under the model, we show that correlations between admixture levels and these phenotypes dissipate over time—especially if the genetic architecture of the phenotypes involves only a small number of loci, or if mating in the admixed population is random with respect to both the admixture levels and the phenotypes. The result has the implication that a trait that once reflected ancestry in a specific source population might lose this ancestry correlation. As a consequence, in human populations, after a sufficient length of time, salient phenotypes that can have social meaning as ancestry markers might no longer bear any relationship to genome-wide genetic ancestry.

scholarly journals Inferring Linkage Disequilibrium Between a Polymorphic Marker Locus and a Trait Locus in Natural Populations

Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 457-467 ◽  
Author(s):  
Z W Luo ◽  
S H Tao ◽  
Z-B Zeng
Keyword(s):  
Linkage Disequilibrium ◽  
Allele Frequency ◽  
Random Mating ◽  
Natural Populations ◽  
Polymorphic Marker ◽  
Marker Locus ◽  
Model Parameters ◽  
Phenotypic Variance ◽  
Wide Range ◽  
Trait Locus

Abstract Three approaches are proposed in this study for detecting or estimating linkage disequilibrium between a polymorphic marker locus and a locus affecting quantitative genetic variation using the sample from random mating populations. It is shown that the disequilibrium over a wide range of circumstances may be detected with a power of 80% by using phenotypic records and marker genotypes of a few hundred individuals. Comparison of ANOVA and regression methods in this article to the transmission disequilibrium test (TDT) shows that, given the genetic variance explained by the trait locus, the power of TDT depends on the trait allele frequency, whereas the power of ANOVA and regression analyses is relatively independent from the allelic frequency. The TDT method is more powerful when the trait allele frequency is low, but much less powerful when it is high. The likelihood analysis provides reliable estimation of the model parameters when the QTL variance is at least 10% of the phenotypic variance and the sample size of a few hundred is used. Potential use of these estimates in mapping the trait locus is also discussed.

scholarly journals Genomic and demographic processes differentially influence genetic variation across the X chromosome

2021 ◽  
Author(s):  
Daniel J. Cotter ◽  
Timothy H. Webster ◽  
Melissa A. Wilson
Keyword(s):  
Genetic Diversity ◽  
Genetic Variation ◽  
Linkage Disequilibrium ◽  
X Chromosome ◽  
Global Scale ◽  
Careful Consideration ◽  
Human Populations ◽  
Evolutionary Forces ◽  
Ideal System ◽  
Demographic Patterns

AbstractMutation, recombination, selection, and demography affect genetic variation across the genome. Increased mutation and recombination both lead to increases in genetic diversity in a region-specific manner, while complex demographic patterns shape patterns of diversity on a more global scale. The X chromosome is particularly interesting because it contains several distinct regions that are subject to different combinations and strengths of these processes, notably the pseudoautosomal regions (PARs) and the X-transposed region (XTR). The X chromosome thus can serve as a unique model for studying how genetic and demographic forces act in different contexts to shape patterns of observed variation. Here we investigate diversity, divergence, and linkage disequilibrium in each region of the X chromosome using genomic data from 26 human populations. We find that both diversity and substitution rate are consistently elevated in PAR1 and the XTR compared to the rest of the X chromosome. In contrast, linkage disequilibrium is lowest in PAR1 and highest on the non-recombining X chromosome, with the XTR falling in between, suggesting that the XTR (usually included in the non-recombining X) may need to be considered separately in future studies. We also observed strong population-specific effects on genetic diversity; not only does genetic variation differ on the X and autosomes among populations, but the effects of linked selection on the X relative to autosomes have been shaped by population-specific history. The substantial variation in patterns of variation across these regions provides insight into the unique evolutionary history contained within the X chromosome.Significance StatementDemography and selection affect the X chromosome differently from non-sex chromosomes. However, the X chromosome can be subdivided into multiple distinct regions that facilitate even more fine-scaled assessment of these processes. Here we study regions of the human X chromosome in 26 populations to find evidence that recombination may be mutagenic in humans and that the X-transposed region may undergo recombination. Further we observe that the effects of selection and demography act differently on the X chromosome relative to the autosomes across human populations. Together, our results highlight profound regional differences across the X chromosome, simultaneously making it an ideal system for exploring the action of evolutionary forces as well as necessitating its careful consideration and treatment in genomic analyses.

Sign in / Sign up

Export Citation Format

Share Document