Ancestral Population Research Articles

Integrative taxonomy supports the recognition of four taxa in the Notholaena trichomanoides complex (Pteridaceae) in Cuba

Abstract With nearly 40 species, the fern genus Notholaena has its evolutionary centre in the deserts of Mexico and the southwestern United States. Previous studies have focused on assessing the monophyly of the genus and the patterns of farina evolution, but little attention has been given to species complexes. Notholaena trichomanoides s.l. is endemic to the Greater Antilles, growing on all four islands. Although at least two varieties have been described, many authors have hesitated to recognize them and have treated this complex as only one taxon. A multivariate morphometric analysis including 80 representatives of N. trichomanoides from the Greater Antilles allowed us to recognize four morphological groups. Twenty individuals from seven populations representing all these morphological groups were sampled in Cuba. Differences among the four lineages were supported by molecular phylogenetics (including three plastid and two nuclear markers), molecular species delimitation, morphology and geological preferences. Ploidy levels inferred using spore sizes calibrated by chromosome counts revealed the existence of diploid and tetraploid lineages within the complex. Time-calibrated trees suggest that the divergence of the common ancestral populations of N. trichomanoides s.l. and those of its sister taxon N. ekmanii occurred between the Middle Miocene and the Miocene–Pliocene boundary followed by a recent diversification within the complex, ranging between the Middle Pliocene and the Middle Pleistocene.

A comparison of genomic diversity and demographic history of the North Atlantic and Southwest Atlantic southern right whales.

Right whales (genus Eubalaena) were among the first, and most extensively pursued, targets of commercial whaling. However, understanding the impacts of this persecution requires knowledge of the demographic histories of these species prior to exploitation. We used deep whole genome sequencing (~40×) of 12 North Atlantic (E. glacialis) and 10 Southwest Atlantic southern (E. australis) right whales to quantify contemporary levels of genetic diversity and infer their demographic histories over time. Using coalescent- and identity-by-descent-based modelling to estimate ancestral effective population sizes from genomic data, we demonstrate that North Atlantic right whales have lived with smaller effective population sizes (Ne) than southern right whales in the Southwest Atlantic since their divergence and describe the decline in both populations around the time of whaling. North Atlantic right whales exhibit reduced genetic diversity and longer runs of homozygosity leading to higher inbreeding coefficients compared to the sampled population of southern right whales. This study represents the first comprehensive assessment of genome-wide diversity of right whales in the western Atlantic and underscores the benefits of high coverage, genome-wide datasets to help resolve long-standing questions about how historical changes in effective population size over different time scales shape contemporary diversity estimates. This knowledge is crucial to improve our understanding of the right whales' history and inform our approaches to address contemporary conservation issues. Understanding and quantifying the cumulative impact of long-term small Ne, low levels of diversity and recent inbreeding on North Atlantic right whale recovery will be important next steps.

Missing Giants: Predictions on Dust-obscured Galaxy Stellar Mass Assembly Throughout Cosmic Time

Due to their extremely dust-obscured nature, much uncertainty still exists surrounding the stellar mass growth and content in dusty, star-forming galaxies (DSFGs) at z > 1. In this work, we present a numerical model built using empirical data on DSFGs to estimate their stellar mass contributions across the first ∼10 Gyr of cosmic time. We generate a dust-obscured stellar mass function that extends beyond the mass limit of star-forming stellar mass functions in the literature, and predict that massive DSFGs constitute as much as 50%–100% of all star-forming galaxies with M ≥1011 M ⊙ at z > 1. We predict the number density of massive DSFGs and find general agreement with observations, although more data is needed to narrow wide observational uncertainties. We forward-model mock massive DSFGs to their quiescent descendants and find remarkable agreement with observations from the literature demonstrating that, to first order, massive DSFGs are a sufficient ancestral population to describe the prevalence of massive quiescent galaxies at z > 1. We predict that massive DSFGs and their descendants contribute as much as 25%–60% to the cosmic stellar mass density during the peak of cosmic star formation, and predict an intense epoch of population growth during the ∼1 Gyr from z = 6 to 3 during which the majority of the most massive galaxies at high-z grow and then quench. Future studies seeking to understand massive galaxy growth and evolution in the early universe should strategize synergies with data from the latest observatories (e.g., JWST and the Atacama Large Millimeter/submillimeter Array) to better include the heavily dust-obscured galaxy population.

Potential Contribution of Ancient Introgression to the Evolution of a Derived Reproductive Strategy in Ricefishes.

Transitions from no parental care to extensive care are costly and involve major changes in life history, behavior, and morphology. Nevertheless, in Sulawesi ricefishes, pelvic brooding evolved from transfer brooding in two distantly related lineages within the genera Adrianichthys and Oryzias, respectively. Females of pelvic brooding species carry their eggs attached to their belly until the fry hatches. Despite their phylogenetic distance, both pelvic brooding lineages share a set of external morphological traits. A recent study found no direct gene flow between pelvic brooding lineages, suggesting independent evolution of the derived reproductive strategy. Convergent evolution can, however, also rely on repeated sorting of preexisting variation of an admixed ancestral population, especially when subjected to similar external selection pressures. We thus used a multispecies coalescent model and D-statistics to identify gene-tree-species-tree incongruencies, to evaluate the evolution of pelvic brooding with respect to interspecific gene flow not only between pelvic brooding lineages but also between pelvic brooding lineages and other Sulawesi ricefish lineages. We found a general network-like evolution in Sulawesi ricefishes, and as previously reported, we detected no gene flow between the pelvic brooding lineages. Instead, we found hybridization between the ancestor of pelvic brooding Oryzias and the common ancestor of the Oryzias species from the Lake Poso area. We further detected signs of introgression within the confidence interval of a quantitative trait locus associated with pelvic brooding in O. eversi. Our results hint toward a contribution of ancient standing genetic variation to the evolution of pelvic brooding in Oryzias.

Next‐generation sequencing reveals hidden genomic diversity in glacial relicts: A case study of Meesia triquetra

AbstractThe recent development of genetic methods has facilitated the identification of cryptic species across different groups of organisms, including plants. However, next‐generation sequencing has rarely been used to study cryptic speciation in plants, especially in bryophytes, organisms with a dominant haploid life phase. The ability to capture variation across the whole genome makes this method an effective tool for distinguishing cryptic lineages. We have focused on the genetic structure of the moss Meesia triquetra along the Alps‐to‐Scandinavia transect. We detected the presence of the two genetically critically different lineages of M. triquetra in Europe. These lineages overlap in both morphological characters of the gametophyte and distribution ranges. However, they considerably differ in ecological preferences to groundwater pH. While lineage 1 occupied alkaline to subneutral fens, lineage 2 occurred in fens saturated with neutral to acidic water. We consider the entities cryptic species with respect to genetic and ecological differences but the absence of morphological features necessary for determining the entities. We hypothesize that fragmentation of the ancestral population of the moss in geographically isolated refugia differing in the commonness of acidic and alkaline substrates led to consequent long‐term adaptation to different environmental conditions, then drove diversification in M. triquetra.

Characterization and Valorization of Maize Landraces from Aosta Valley.

While there is a rich collection of maize germplasm from Italy, it lacks genetic resources from the Aosta Valley, an isolated mountain region where landraces have been preserved in the absence of modern germplasm introductions. These local materials, which are still cultivated mainly at household level, can have high importance from a genetic and historical point of view. In the present study, five landraces named, after the collecting sites, Arnad, Arnad-Crest, Châtillon, Entrebin and Perloz, were sampled in Aosta Valley and subjected to historic, morphologic and genetic characterization. This study provided evidence for the landraces' long presence in Aosta Valley, a significant genetic variability and differentiation among the investigated landraces. Globally, 67 different alleles were detected ranging from 4 for markers phi127 and p-bnlg176 to 10 for phi031, with a mean of 6.7 alleles per locus. Observed heterozygosity levels were comprised from 0.16 to 0.51 and are generalkly lower than expected heterozigosity supporting fixation at some loci. STRUCTURE analysis revealed clear separation between accessions revealing the presence of four ancestral populations. This may be explained by the long reproductive isolation experienced by these materials. Finally, morphological observations confirm the high diversity between landraces revealing that they generally have flint kernels, variable color from yellow to dark red (Châtillon) while Perloz showed kernels with an apical beak. The present work confirms the importance of mountain areas in conserving biodiversity and increases the rich Italian maize germplasm with materials well adapted to marginal areas. Such new genetic variability may be used to breed new materials for more resilient agriculture.

The infinitesimal model with dominance.

The classical infinitesimal model is a simple and robust model for the inheritance of quantitative traits. In this model, a quantitative trait is expressed as the sum of a genetic and an environmental component, and the genetic component of offspring traits within a family follows a normal distribution around the average of the parents' trait values, and has a variance that is independent of the parental traits. In previous work, we showed that when trait values are determined by the sum of a large number of additive Mendelian factors, each of small effect, one can justify the infinitesimal model as a limit of Mendelian inheritance. In this paper, we show that this result extends to include dominance. We define the model in terms of classical quantities of quantitative genetics, before justifying it as a limit of Mendelian inheritance as the number, M, of underlying loci tends to infinity. As in the additive case, the multivariate normal distribution of trait values across the pedigree can be expressed in terms of variance components in an ancestral population and probabilities of identity by descent determined by the pedigree. Now, with just first-order dominance effects, we require two-, three-, and four-way identities. We also show that, even if we condition on parental trait values, the "shared" and "residual" components of trait values within each family will be asymptotically normally distributed as the number of loci tends to infinity, with an error of order 1/M. We illustrate our results with some numerical examples.

Tools of genomic medicine for clinical practice: The example of psychiatry.

Most psychiatric disorders are moderate to highly heritable, often with different genetic architectures. Although genetic research in psychiatry has progressed, its findings, interpretation, and impact on clinical psychiatry are unknown to most mental healthcare professionals. This article addresses key genetic concepts to understand some clinical entities, emphasizing genetic terminology and types of mutations. Particularly, we describe the role of heritability in the early days of psychiatry genetic research, the most used study designs, and their main objectives. On the other hand, we review some genetic and genomic databases useful for clinical practice. These include Online Mendelian Inheritance in Man, ClinVar, Ensembl, and The Single Nucleotide Polymorphism Database. Finally, a clinical vignette is presented in which we can apply genomic medicine tools. Since the evidence in psychiatric genetics is based on studies carried out in European or North American ancestral populations, we must develop local studies to increase the knowledge and application of genomic medicine on underrepresented populations.

Admixture mapping implicates 13q33.3 as ancestry-of-origin locus for Alzheimer disease in Hispanic and Latino populations.

Alzheimer disease (AD) is the most common form of senile dementia, with high incidence late in life in many populations including Caribbean Hispanic (CH) populations. Such admixed populations, descended from more than one ancestral population, can present challenges for genetic studies, including limited sample sizes and unique analytical constraints. Therefore, CH populations and other admixed populations have not been well represented in studies of AD, and much of the genetic variation contributing to AD risk in these populations remains unknown. Here, we conduct genome-wide analysis of AD in multiplex CH families from the Alzheimer Disease Sequencing Project (ADSP). We developed, validated, and applied an implementation of a logistic mixed model for admixture mapping with binary traits that leverages genetic ancestry to identify ancestry-of-origin loci contributing to AD. We identified three loci on chromosome 13q33.3 associated with reduced risk of AD, where associations were driven by Native American (NAM) ancestry. This AD admixture mapping signal spans the FAM155A, ABHD13, TNFSF13B, LIG4, and MYO16 genes and was supported by evidence for association in an independent sample from the Alzheimer's Genetics in Argentina-Alzheimer Argentina consortium (AGA-ALZAR) study with considerable NAM ancestry. We also provide evidence of NAM haplotypes and key variants within 13q33.3 that segregate with AD in the ADSP whole-genome sequencing data. Interestingly, the widely used genome-wide association study approach failed to identify associations in this region. Our findings underscore the potential of leveraging genetic ancestry diversity in recently admixed populations to improve genetic mapping, in this case for AD-relevant loci.

Are 150 km of open sea enough? Gene flow and population differentiation in a bat-pollinated columnar cactus.

Genetic differentiations and phylogeographical patterns are controlled by the interplay between spatial isolation and gene flow. To assess the extent of gene flow across an oceanic barrier, we explored the effect of the separation of the peninsula of Baja California on the evolution of mainland and peninsular populations of the long-lived columnar cactus Stenocereus thurberi. We analyzed twelve populations throughout the OPC distribution range to assess genetic diversity and structure using chloroplast DNA sequences. Genetic diversity was higher (Hd = 0.81), and genetic structure was lower (GST = 0.143) in mainland populations vs peninsular populations (Hd = 0.71, GST = 0.358 respectively). Genetic diversity was negatively associated with elevation but positively with rainfall. Two mainland and one peninsular ancestral haplotypes were reconstructed. Peninsular populations were as isolated among them as with mainland populations. Peninsular haplotypes formed a group with one mainland coastal population, and populations across the gulf shared common haplotypes giving support to regular gene flow across the Gulf. Gene flow is likely mediated by bats, the main pollinators and seed dispersers. Niche modeling suggests that during the Last Glacial Maximum (c. 130 ka), OPC populations shrank to southern locations. Currently, Stenocereus thurberi populations are expanding, and the species is under population divergence despite ongoing gene flow. Ancestral populations are located on the mainland and although vicariant peninsular populations cannot be ruled out, they are likely the result of gene flow across the seemingly formidable barrier of the Gulf of California. Still, unique haplotypes occur in the peninsula and the mainland, and peninsular populations are more structured than those on the mainland.

The Metasequoia genome and evolutionary relationships among redwoods

Redwood trees (Sequoioideae), including Metasequoia glyptostroboides (dawn redwood), Sequoiadendron giganteum (giant sequoia), and Sequoia sempervirens (coast redwood), are threatened and widely recognized iconic tree species. Genomic resources for redwood trees could provide clues to their evolutionary relationships. Here, we report the 8-Gb reference genome of M. glyptostroboides and a comparative analysis with two related species. More than 62% of the M. glyptostroboides genome is composed of repetitive sequences. Clade-specific bursts of long terminal repeat retrotransposons may have contributed to genomic differentiation in the three species. The chromosomal synteny between M. glyptostroboides and S. giganteum is extremely high, whereas there has been significant chromosome reorganization in S. sempervirens. Phylogenetic analysis of marker genes indicates that S. sempervirens is an autopolyploid, and more than 48% of the gene trees are incongruent with the species tree. Results of multiple analyses suggest that incomplete lineage sorting (ILS) rather than hybridization explains the inconsistent phylogeny, indicating that genetic variation among redwoods may be due to random retention of polymorphisms in ancestral populations. Functional analysis of ortholog groups indicates that gene families of ion channels, tannin biosynthesis enzymes, and transcription factors for meristem maintenance have expanded in S. giganteum and S. sempervirens, which is consistent with their extreme height. As a wetland-tolerant species, M. glyptostroboides shows a transcriptional response to flooding stress that is conserved with that of analyzed angiosperm species. Our study offers insights into redwood evolution and adaptation and provides genomic resources to aid in their conservation and management.

Cross-ancestry genome-wide association meta-analyses of hippocampal and subfield volumes.

The hippocampus is critical for memory and cognition and neuropsychiatric disorders, and its subfields differ in architecture and function. Genome-wide association studies on hippocampal and subfield volumes are mainly conducted in European populations; however, other ancestral populations are under-represented. Here we conduct cross-ancestry genome-wide association meta-analyses in 65,791 individuals for hippocampal volume and 38,977 for subfield volumes, including 7,009 individuals of East Asian ancestry. We identify 339 variant-trait associations at P < 1.13 × 10-9 for 44 hippocampal traits, including 23 new associations. Common genetic variants have similar effects on hippocampal traits across ancestries, although ancestry-specific associations exist. Cross-ancestry analysis improves the fine-mapping precision and the prediction performance of polygenic scores in under-represented populations. These genetic variants are enriched for Wnt signaling and neuron differentiation and affect cognition, emotion and neuropsychiatric disorders. These findings may provide insight into the genetic architectures of hippocampal and subfield volumes.

The ricebean genome provides insight into Vigna genome evolution and facilitates genetic enhancement.

The ricebean genome provides insight into Vigna genome evolution and facilitates genetic enhancement.

Genetic diversity and selection signatures in a gene bank panel of maize inbred lines from Southeast Europe compared with two West European panels

Southeast Europe (SEE) is a very important maize-growing region, comparable to the Corn belt region of the United States, with similar dent germplasm (dent by dent hybrids). Historically, this region has undergone several genetic material swaps, following the trends in the US, with one of the most significant swaps related to US aid programs after WWII. The imported accessions used to make double-cross hybrids were also mixed with previously adapted germplasm originating from several more distant OPVs, supporting the transition to single cross-breeding. Many of these materials were deposited at the Maize Gene Bank of the Maize Research Institute Zemun Polje (MRIZP) between the 1960s and 1980s. A part of this Gene Bank (572 inbreds) was genotyped with Affymetrix Axiom Maize Genotyping Array with 616,201 polymorphic variants. Data were merged with two other genotyping datasets with mostly European flint (TUM dataset) and dent (DROPS dataset) germplasm. The final pan-European dataset consisted of 974 inbreds and 460,243 markers. Admixture analysis showed seven ancestral populations representing European flint, B73/B14, Lancaster, B37, Wf9/Oh07, A374, and Iodent pools. Subpanel of inbreds with SEE origin showed a lack of Iodent germplasm, marking its historical context. Several signatures of selection were identified at chromosomes 1, 3, 6, 7, 8, 9, and 10. The regions under selection were mined for protein-coding genes and were used for gene ontology (GO) analysis, showing a highly significant overrepresentation of genes involved in response to stress. Our results suggest the accumulation of favorable allelic diversity, especially in the context of changing climate in the genetic resources of SEE.

Similarity and diversity of genetic architecture for complex traits between East Asian and European populations

BackgroundGenome-wide association studies have detected a large number of single-nucleotide polymorphisms (SNPs) associated with complex traits in diverse ancestral groups. However, the trans-ethnic similarity and diversity of genetic architecture is not well understood currently.ResultsBy leveraging summary statistics of 37 traits from East Asian (Nmax=254,373) or European (Nmax=693,529) populations, we first evaluated the trans-ethnic genetic correlation (ρg) and found substantial evidence of shared genetic overlap underlying these traits between the two populations, with {widehat{rho }}_{g} ranging from 0.53 (se = 0.11) for adult-onset asthma to 0.98 (se = 0.17) for hemoglobin A1c. However, 88.9% of the genetic correlation estimates were significantly less than one, indicating potential heterogeneity in genetic effect across populations. We next identified common associated SNPs using the conjunction conditional false discovery rate method and observed 21.7% of trait-associated SNPs can be identified simultaneously in both populations. Among these shared associated SNPs, 20.8% showed heterogeneous influence on traits between the two ancestral populations. Moreover, we demonstrated that population-common associated SNPs often exhibited more consistent linkage disequilibrium and allele frequency pattern across ancestral groups compared to population-specific or null ones. We also revealed population-specific associated SNPs were much likely to undergo natural selection compared to population-common associated SNPs.ConclusionsOur study provides an in-depth understanding of similarity and diversity regarding genetic architecture for complex traits across diverse populations, and can assist in trans-ethnic association analysis, genetic risk prediction, and causal variant fine mapping.

Five long-distance dispersals shaped the major intercontinental disjunctions in Tectariaceae s.l. (Polypodiales, Polypodiopsida)

Intercontinental disjunct distributions can arise either from vicariance, from long-distance dispersal, or through extinction of an ancestral population with a broader distribution. Tectariaceae s.l., a clade of ferns in Polypodiales with ca. 300 species mainly distributed in the tropics and subtropics, provide an excellent opportunity to investigate global distribution patterns. Here, we assembled a dataset of eight plastid markers and one nuclear marker of 636 (92% increase of the earlier largest sampling) accessions representing ca. 210 species of all eight genera in Tectariaceae s.l. (Arthropteridaceae, Pteridryaceae, and Tectariaceae s.s.) and 35 species of other families of eupolypods Ⅰ. A new phylogeny is reconstructed to study the biogeography and trait-associated diversification. Our major results include: (1) a distinct lineage of Tectaria sister to the rest of the American Tectaria is identified; (2) Tectariaceae s.l., and the three families: Arthropteridaceae (Arthropteris), Pteridryaceae (Draconopteris, Malaifilix, Polydictyum, Pteridrys), and Tectariaceae s.s. (Hypoderris, Tectaria, and Triplophyllum), might have all originated in late Cretaceous; (3) only five intercontinental dispersals occurred in Pteridryaceae and Tectariaceae s.s. giving rise to their current intercontinental disjunction; (4) we provide the second evidence in ferns that a long-distance dispersal between Malesia and Americas during the Paleocene to Eocene led to the establishment/origin of a new genus (Draconopteris); and (5) diversification rate of each state of leaf dissection is different, and the lowest is in the simple-leaved taxa.

A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations.

Abstinence rates among smokers attempting to quit remain low despite the wide availability and accessibility of pharmacological smoking cessation treatments. In addition, the prevalence of cessation attempts and abstinence differs by individual-level social factors such as race and ethnicity. Clinical treatment of nicotine dependence also continues to be challenged by individual-level variability in effectiveness to promote abstinence. The use of tailored smoking cessation strategies that incorporate information on individual-level social and genetic factors hold promise, although additional pharmacogenomic knowledge is still needed. In particular, genetic variants associated with pharmacological responses to smoking cessation treatment have generally been conducted in populations with participants that self-identify as White race or who are determined to be of European genetic ancestry. These results may not adequately capture the variability across all smokers as a result of understudied differences in allele frequencies across genetic ancestry populations. This suggests that much of the current pharmacogenetic study results for smoking cessation may not apply to all populations. Therefore, clinical application of pharmacogenetic results may exacerbate health inequities by racial and ethnic groups. This scoping review examines the extent to which racial, ethnic, and ancestral groups that experience differences in smoking rates and smoking cessation are represented in the existing body of published pharmacogenetic studies of smoking cessation. We will summarize results by race, ethnicity, and ancestry across pharmacological treatments and study designs. We will also explore current opportunities and challenges in conducting pharmacogenomic research on smoking cessation that encourages greater participant diversity, including practical barriers to clinical utilization of pharmacological smoking cessation treatment and clinical implementation of pharmacogenetic knowledge.

Pervasive incomplete lineage sorting illuminates speciation and selection in primates.

Incomplete lineage sorting (ILS) causes the phylogeny of some parts of the genome to differ from the species tree. In this work, we investigate the frequencies and determinants of ILS in 29 major ancestral nodes across the entire primate phylogeny. We find up to 64% of the genome affected by ILS at individual nodes. We exploit ILS to reconstruct speciation times and ancestral population sizes. Estimated speciation times are much more recent than genomic divergence times and are in good agreement with the fossil record. We show extensive variation of ILS along the genome, mainly driven by recombination but also by the distance to genes, highlighting a major impact of selection on variation along the genome. In many nodes, ILS is reduced more on the X chromosome compared with autosomes than expected under neutrality, which suggests higher impacts of natural selection on the X chromosome. Finally, we show an excess of ILS in genes with immune functions and a deficit of ILS in housekeeping genes. The extensive ILS in primates discovered in this study provides insights into the speciation times, ancestral population sizes, and patterns of natural selection that shape primate evolution.

Polygenic risk score calibration and association with breast cancer in diverse ancestries.

10505 Background: Polygenic risk scores (PRS) have been shown to substantially improve breast cancer (BC) risk prediction when incorporated into traditional risk assessment models. However, PRS developed primarily in women of European ancestry have shown poor performance when applied to non-European populations. We previously described development and validation of a multiple-ancestry PRS (MA-PRS) that is based on individual ancestral genetic composition. MA-PRS has been incorporated into the Tyrer-Cuzick model for use in clinical practice and has been shown to provide independent value to the model. Here, we describe performance of the MA-PRS in a large cohort of women from diverse ancestral backgrounds. Methods: The study cohort included 203,586 patients who were referred for hereditary cancer testing and negative for pathogenic variants in genes associated with BC. MA-PRS was calculated as previously described based on 149 SNPs (93 BC and 56 ancestry-informative). Association of MA-PRS with invasive BC status (affected vs unaffected) was analyzed using logistic regression adjusted for personal and family cancer history, age, and ancestry. Calibration was assessed by examining the MA-PRS distribution within unaffected patients, and through goodness-of-fit tests. All analyses were conducted within the full cohort and within ancestral subpopulations. Odds ratios (ORs) are reported per standard deviation. Results: One-fifth (43,782/203,586, 21.5%) of patients were diagnosed with invasive BC, and 60,657 (29.8%) of patients reported BC in a first degree relative. The MA-PRS distribution was centered around zero among unaffected patients overall and within each subpopulation. MA-PRS significantly improved BC risk prediction over clinical factors in the full cohort (OR = 1.43, 95% CI:1.41-1.44) and within each ancestral subpopulation (Table). The strongest associations were observed in Ashkenazi Jewish (OR = 1.56, 95% CI:1.39-1.76) and South Asian (OR = 1.49,95% CI: 1.23-1.81) populations. The top decile of the MA-PRS consistently identified patients with two-fold increased risk of developing BC. Goodness-of-fit tests showed that the MA-PRS was well calibrated and predicted BC risk accurately in the tails of the distribution for both European and non-European women. Conclusions: The breast cancer MA-PRS based on genetic ancestral composition is well-calibrated and strongly associated with BC in all tested ancestral populations. Incorporation of PRS adds independent information to risk models and supports equitable access to personalized BC risk management. [Table: see text]

On the genes, genealogies, and geographies of Quebec.

Population genetic models only provide coarse representations of real-world ancestry. We used a pedigree compiled from 4 million parish records and genotype data from 2276 French and 20,451 French Canadian individuals to finely model and trace French Canadian ancestry through space and time. The loss of ancestral French population structure and the appearance of spatial and regional structure highlights a wide range of population expansion models. Geographic features shaped migrations, and we find enrichments for migration, genetic, and genealogical relatedness patterns within river networks across regions of Quebec. Finally, we provide a freely accessible simulated whole-genome sequence dataset with spatiotemporal metadata for 1,426,749 individuals reflecting intricate French Canadian population structure. Such realistic population-scale simulations provide opportunities to investigate population genetics at an unprecedented resolution.