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152 results for “polygenes”
Data from: Landscape genomics of Colorado potato beetle provides evidence of polygenic adaptation to insecticides
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Supplemental data for: Development and validation of a polygenic risk score for stroke in the Chinese population
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Polygenic selection within a single generation leads to subtle divergence among ecological niches
<p>Selection on standing genetic variation may be effective enough to allow for adaptation to distinct niche environments within a single generation. Minor allele frequency changes at multiple, redundant loci of small effect can produce remarkable phenotypic shifts. Yet, demonstrating rapid adaptation via polygenic selection in the wild remains challenging. Here we harness natural replicate populations that experience similar selection pressures and harbor high within-, yet negligible among-population genetic variation. Such populations can be found among the teleost Fundulus heteroclitus which inhabits marine estuaries characterized by high environmental heterogeneity. We identify 10,861 single nucleotide polymorphisms in F. heteroclitus that belong to a single, panmictic population yet reside in environmentally distinct niches (one coastal basin and three replicate tidal ponds). By sampling at two time-points within a single generation we quantify both allele frequency change within as well as spatial divergence among niche subpopulations. We observe few individually significant allele frequency changes yet find that the number of moderate changes exceeds the neutral expectation by 10-100%. We find allele frequency changes to be significantly concordant in both direction and magnitude among all niche subpopulations, suggestive of parallel selection. In addition, within-generation allele frequency changes generate subtle but significant divergence among niches, indicative of local adaptation. Although we cannot distinguish between selection and genotype-dependent migration as drivers of within-generation allele frequency changes, the trait/s determining fitness and/or migration likelihood appear to be polygenic. In heterogeneous environments, polygenic selection and polygenic, genotype-dependent migration offer conceivable mechanisms for within-generation, local adaptation to distinct niches.</p>
Data from: RAD-sequencing reveals within-generation polygenic selection in response to anthropogenic organic and metal contamination in North Atlantic Eels
Measuring the effects of selection on the genome imposed by human-altered environment is currently a major goal in ecological genomics. Given the polygenic basis of most phenotypic traits, quantitative genetic theory predicts that selection is expected to cause subtle allelic changes among covarying loci rather than pronounced changes at few loci of large effects. The goal of this study was to test for the occurrence of polygenic selection in both North Atlantic eels (European Eel, Anguilla anguilla and American Eel, A. rostrata), using a method that searches for covariation among loci that would discriminate eels from "control" vs. "polluted" environments and be associated with specific contaminants acting as putative selective agents. RAD-seq libraries resulted in 23,659 and 14,755 filtered loci for the European and American Eels respectively. A total of 142 and 141 covarying markers discriminating European and American Eels from "control" vs. "polluted" sampling localities were obtained using the Random Forest algorithm. Distance-based redundancy analyses (db-RDAs) were used to assess the relationships between these covarying markers and concentration of 34 contaminants measured for each individual eel. PCB153, 4'4'DDE and selenium were associated with covarying markers for both species, thus pointing to these contaminants as major selective agents in contaminated sites . Gene enrichment analyses suggested that sterol regulation plays an important role in the differential survival of eels in "polluted" environment. This study illustrates the power of combining methods for detecting signals of polygenic selection and for associating variation of markers with putative selective agents in studies aiming at documenting the dynamics of selection at the genomic level, and particularly so in human altered environments.
Data from: Effect of polygenic load on striatal dopaminergic deterioration in Parkinson's disease
Objective: To investigate the effect of polygenic load on the progression of striatal dopaminergic dysfunction in patients with Parkinson's disease (PD). Methods: Using data from 335 PD patients in the Parkinson's Progression Markers Initiative (PPMI) database, we investigated the longitudinal association of PD-associated polygenic load with changes in striatal dopaminergic activity as measured by 123I-N-3-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT) over 4 years. PD-associated polygenic load was estimated by calculating weighted genetic risk scores (GRS) using: i) all available 27 PD-risk single nucleotide polymorphisms (SNPs) in the PPMI database (GRS1); and ii) 23 SNPs with minor allele frequency > 0.05 (GRS2). Results: GRS1 and GRS2 were correlated with younger age-at-onset in PD patients (GRS1, Spearman's rho = -0.128, p = 0.019; GRS2, Spearman's rho = -0.109, p = 0.047). Although GRS1 did not show an association with changes in striatal 123I-FP-CIT availability, GRS2 was associated with a slower decline of striatal dopaminergic activity (interactions with disease duration in linear mixed model; caudate nucleus, estimate = 0.399, SE = 0.165, p = 0.028; putamen, estimate = 0.396, SE = 0.137, p = 0.016). Conclusions: Our results suggest that genetic factors for PD risk may have heterogeneous effects on the striatal dopaminergic degeneration, and some factors may be associated with a slower decline of dopaminergic activity. Composition of PD-progression specific GRS may be useful in predicting disease progression in patients.
Data from: Reduced signal for polygenic adaptation of height in UK Biobank
Several recent papers have reported strong signals of selection on European polygenic height scores. These analyses used height effect estimates from the GIANT consortium and replication studies. Here, we describe a new analysis based on the the UK Biobank (UKB), a large, independent dataset. We find that the signals of selection using UKB effect estimates are strongly attenuated or absent. We also provide evidence that previous analyses were confounded by population stratification. Therefore, the conclusion of strong polygenic adaptation now lacks support. Moreover, these discrepancies highlight (1) that methods for correcting for population stratification in GWAS may not always be sufficient for polygenic trait analyses, and (2) that claims of differences in polygenic scores between populations should be treated with caution until these issues are better understood.
Data from: Signatures of polygenic adaptation associated with climate across the range of a threatened fish species with high genetic connectivity
Adaptive differences across species' ranges can have important implications for population persistence and conservation management decisions. Despite advances in genomic technologies, detecting adaptive variation in natural populations remains challenging. Key challenges in gene-environment association studies involve distinguishing the effects of drift from those of selection, and identifying subtle signatures of polygenic adaptation. We used paired-end restriction-site associated-DNA sequencing data (6605 biallelic single nucleotide polymorphisms; SNPs) to examine population structure and test for signatures of adaptation across the geographic range of an iconic Australian endemic freshwater fish species, the Murray cod Maccullochella peelii. Two univariate gene-association methods identified 61 genomic regions associated with climate variation. We also tested for subtle signatures of polygenic adaptation using a multivariate method (redundancy analysis; RDA). The RDA analysis suggested that climate (temperature- and precipitation-related variables) and geography had similar magnitudes of effect in shaping the distribution of SNP genotypes across the sampled range of Murray cod. Although there was poor agreement among the candidate SNPs identified by the univariate methods, the top 5% of SNPs contributing to significant RDA axes included 67% of the SNPs identified by univariate methods. We discuss the potential implications of our findings for the management of Murray cod and other species generally, particularly in relation to informing conservation actions such as translocations to improve evolutionary resilience of natural populations. Our results highlight the value of using a combination of different approaches, including polygenic methods, when testing for signatures of adaptation in landscape genomics studies.
Left atrial polygenic scores for "Deep Learning of Left Atrial Structure and Function Provides Link to Atrial Fibrillation Risk"
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Genomic analysis reveals a polygenic architecture of antler morphology in wild red deer (Cervus elaphus)
<p>Sexually-selected traits show large variation and rapid evolution across the animal kingdom, yet genetic variation often persists within populations despite apparent directional selection. A key step in solving this long-standing paradox is to determine the genetic architecture of sexually-selected traits to understand evolutionary drivers and constraints at the genomic level. Antlers are a form of sexual weaponry in male red deer. On the island of Rum, Scotland, males with larger antlers have increased breeding success, yet there has been no evidence of any response to selection at the genetic level. To try and understand the mechanisms underlying this observation, we investigate the genetic architecture of ten antler traits and their principal components using genomic data from >38,000 SNPs. We estimate the heritabilities and genetic correlations of the antler traits using a genomic relatedness approach. We then use genome-wide association and haplotype-based regional heritability to identify regions of the genome underlying antler morphology, and an Empirical Bayes approach to estimate the underlying distributions of allele effect sizes. We show that antler morphology is highly repeatable over an individual's lifetime, heritable, and has a polygenic architecture, and that almost all antler traits are positively genetically correlated with some loci identified as having pleiotropic effects. Our findings suggest that a large mutational target and genetic covariances among antler traits, in part maintained by pleiotropy, are likely to contribute to the maintenance of genetic variation in antler morphology in this population.</p>
Data from: X-chromosome meiotic drive in Drosophila simulans: a QTL approach reveals the complex polygenic determinism of Paris drive suppression
Meiotic drivers are selfish genetic elements that promote their own transmission into the gametes, which results in intragenomic conflicts. In the Paris sex-ratio system of Drosophila simulans, drivers located on the X chromosome prevent the segregation of the heterochromatic Y chromosome during meiosis II, and hence the production of Y-bearing sperm. The resulting sex-ratio bias strongly impacts population dynamics and evolution. Natural selection, which tends to restore an equal sex ratio, favors the emergence of resistant Y chromosomes and autosomal suppressors. This is the case in the Paris sex-ratio system where the drivers became cryptic in most of the natural populations of D. simulans. Here, we used a Quantitative Trait Locus (QTL) mapping approach based on the analysis of 152 highly recombinant inbred lines (RILs) to investigate the genetic determinism of autosomal suppression. The RILs were derived from an advanced intercross between two parental lines, one showing complete autosomal suppression while the other one was sensitive to drive. The confrontation of RIL autosomes with a reference XSR chromosome allowed us to identify two QTLs on chromosome 2 and three on chromosome 3, with strong epistatic interactions. Our findings highlight the multiplicity of actors involved in this intragenomic battle over the sex ratio.
Data from: Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies
Genetic predictions of height differ among human populations and these differences have been interpreted as evidence of polygenic adaptation. These differences were first detected using SNPs genome-wide significantly associated with height, and shown to grow stronger when large numbers of sub-significant SNPs were included, leading to excitement about the prospect of analyzing large fractions of the genome to detect polygenic adaptation for multiple traits. Previous studies of height have been based on SNP effect size measurements in the GIANT Consortium meta-analysis. Here we repeat the analyses in the UK Biobank, a much more homogeneously designed study. We show that polygenic adaptation signals based on large numbers of SNPs below genome-wide significance are extremely sensitive to biases due to uncorrected population structure. More generally, our results imply that typical constructions of polygenic scores are sensitive to population structure and that population-level differences should be interpreted with caution.
Historical rice farming in China linked to contemporary polygenic score differences
<p>Following domestication in the lower Yangtze River valley 9,400 years ago, rice farming spread throughout China and changed lifestyle patterns among Neolithic populations. Here we report evidence that the advent of rice domestication and cultivation may have shaped humans not only culturally but also genetically. Leveraging recent findings from molecular genetics, we construct a number of polygenic scores of behavioural traits and examine their associations with rice cultivation based on a sample of 4,101 individuals recently collected from Mainland China. A total of nine polygenic traits and genotypes are investigated in this study, including polygenic scores of height, body mass index, depression, time discounting, reproduction, educational attainment, risk preference, <i>ADH1B</i> rs1229984 and <i>ALDH2</i> rs671. Two-stage least squares estimates of the county-level percentage of cultivated land devoted to paddy rice on the polygenic score of age at first birth (<i>b</i> = -0.029, <i>p</i> = 0.021) and <i>ALDH2</i> rs671 (<i>b</i> = 0.182, <i>p</i> < 0.001) are both statistically significant and robust to a wide range of potential confounds and alternative explanations. These findings imply that rice farming may influence human evolution in relatively recent human history.</p>
Implementing Polygenic Risk Scores for Breast Cancer Prevention: a Feasibility Study
ClinicalTrials.gov study NCT06922708. IPD Sharing: YES. Countries: 0. Publications: 14.
Polygenic selection within a single generation leads to subtle divergence among ecological niches
Open the record for dataset details and reuse information.
Data from: Signatures of polygenic adaptation associated with climate across the range of a threatened fish species with high genetic connectivity
Open the record for dataset details and reuse information.
Data from: X-chromosome meiotic drive in Drosophila simulans: a QTL approach reveals the complex polygenic determinism of Paris drive suppression
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Genomic analysis reveals a polygenic architecture of antler morphology in wild red deer (Cervus elaphus)
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Data from: Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies
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Supplementary code for: Polygenic local adaptation in metapopulations: a stochastic eco-evolutionary model
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Data from: Effect of partial selfing and polygenic selection on establishment in a new habitat
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
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