Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits.

It remains unknown to what extent gene-gene interactions contribute to complex traits. Here, we introduce a new approach using predicted gene expression to perform exhaustive transcriptome-wide interaction studies (TWISs) for multiple traits across all pairs of genes expressed in several tissue types. Using imputed transcriptomes, we simultaneously reduce the computational challenge and improve interpretability and statistical power. We discover (in the UK Biobank) and replicate (in independent cohorts) several interaction associations, and find several hub genes with numerous interactions. We also demonstrate that TWIS can identify novel associated genes because genes with many or strong interactions have smaller single-locus model effect sizes. Finally, we develop a method to test gene set enrichment of TWIS associations (E-TWIS), finding numerous pathways and networks enriched in interaction associations. Epistasis is may be widespread, and our procedure represents a tractable framework for beginning to explore gene interactions and identify novel genomic targets.

Population links between an insectivorous bird and moths disentangled through national-scale monitoring data.

Insects are key components of food chains, and monitoring data provides new opportunities to identify trophic relationships at broad spatial and temporal scales. Here, combining two monitoring datasets from Great Britain, we reveal how the population dynamics of the blue tit Cyanistes caeruleus are influenced by the abundance of moths - a core component of their breeding diet. We find that years with increased population growth for blue tits correlate strongly with high moth abundance, but population growth in moths and birds is less well correlated; suggesting moth abundance directly affects bird population change. Next, we identify moths that are important components of blue tit diet, recovering associations to species previously identified as key food sources such as the winter moth Operoptera brumata. Our work provides new evidence that insect abundance impacts bird population dynamics in natural communities and provides insight into spatial diet turnover at a national-scale.

Genetic underpinnings of arthropod community distributions in Populus trichocarpa.

Community genetics seeks to understand the mechanisms by which natural genetic variation in heritable host phenotypes can encompass assemblages of organisms such as bacteria, fungi, and many animals including arthropods. Prior studies that focused on plant genotypes have been unable to identify genes controlling community composition, a necessary step to predict ecosystem structure and function as underlying genes shift within plant populations. We surveyed arthropods within an association population of Populus trichocarpa in three common gardens to discover plant genes that contributed to arthropod community composition. We analyzed our surveys with traditional single-trait genome-wide association analysis (GWAS), multitrait GWAS, and functional networks built from a diverse set of plant phenotypes. Plant genotype was influential in structuring arthropod community composition among several garden sites. Candidate genes important for higher level organization of arthropod communities had broadly applicable functions, such as terpenoid biosynthesis and production of dsRNA binding proteins and protein kinases, which may be capable of targeting multiple arthropod species. We have demonstrated the ability to detect, in an uncontrolled environment, individual genes that are associated with the community assemblage of arthropods on a host plant, further enhancing our understanding of genetic mechanisms that impact ecosystem structure.

Disentangling differing relationships between internalizing disorders and alcohol use.

Both internalizing disorders and alcohol use have dramatic, wide-spread implications for global health. Previous work has established common phenotypic comorbidity among these disorders, as well as shared genetic variation underlying them both. We used genomic structural equation modeling to investigate the shared genetics of internalizing, externalizing, and alcohol use traits, as well as to explore whether specific domains of internalizing symptoms mediate the contrasting relationships with problematic alcohol use compared to alcohol consumption. We also examined patterns of genetic correlations between similar traits within additional Finnish and East Asian ancestry groups. When the shared genetic influence of externalizing psychopathology was accounted for, the genetic effect of internalizing traits on alcohol use was reduced, suggesting the important role of common genetic factors underlying multiple psychiatric disorders and their genetic influences on comorbidity of internalizing and alcohol use traits. Individual internalizing domains had contrasting effects on frequency of alcohol consumption, which demonstrate the complex system of pleiotropy that exists, even within similar disorders, and can be missed when evaluating only relationships among formal diagnoses. Future work must consider the broad effects of shared psychopathology along with the fine-scale effects of heterogeneity within disorders to more fully understand the biology underlying complex traits.

Mechanisms underpinning community stability along a latitudinal gradient: Insights from a niche-based approach.

At large scales, the mechanisms underpinning stability in natural communities may vary in importance due to changes in species composition, mean abundance, and species richness. Here we link species characteristics (niche positions) and community characteristics (richness and abundance) to evaluate the importance of stability mechanisms in 156 butterfly communities monitored across three European countries and spanning five bioclimatic regions. We construct niche-based hierarchical structural Bayesian models to explain first differences in abundance, population stability, and species richness between the countries, and then explore how these factors impact community stability both directly and indirectly (via synchrony and population stability). Species richness was partially explained by the position of a site relative to the niches of the species pool, and species near the centre of their niche had higher average population stability. The differences in mean abundance, population stability, and species richness then influenced how much variation in community stability they explained across the countries. We found, using variance partitioning, that community stability in Finnish communities was most influenced by community abundance, whereas this aspect was unimportant in Spain with species synchrony explaining most variation; the UK was somewhat intermediate with both factors explaining variation. Across all countries, the diversity-stability relationship was indirect with species richness reducing synchrony which increased community stability, with no direct effects of species richness. Our results suggest that in natural communities, biogeographical variation observed in key drivers of stability, such as population abundance and species richness, leads to community stability being limited by different factors and that this can partially be explained due to the niche characteristics of the European butterfly assemblage.

Characterizing the trophy hunting debate on Twitter.

Social media is an arena of debate for contentious political and social topics. One conservation topic debated online is the acceptability of trophy hunting, a debate that has implications for national and international policy. We used a mixed-methods approach (grounded theory and quantitative clustering) to identify themes in the trophy hunting debate on Twitter. We examined commonly co-occurring categories that describe people's stances on trophy hunting. We identified 12 categories and 4 preliminary archetypes opposing trophy hunting-activism, scientific, condemning, and objecting-whose opposition derived from different moral reasoning. Few tweets (22) in our sample of 500 supported trophy hunting, whereas 350 opposed it. The debate was hostile; 7% of tweets in our sample were categorized as abusive. Online debates can be unproductive, and our findings may be important for stakeholders wishing to effectively engage in the trophy hunting debate on Twitter. More generally, we contend that because social media is increasingly influential, it is important to formally contextualize public responses to contentious conservation topics in order to aid communication of conservation evidence and to integrate diverse public perspectives in conservation practice.

Caracterización del debate sobre la cacería de trofeos en Twitter Resumen Las redes sociales son arenas de debate para temas políticos y sociales polémicos. Un tema de conservación que se debate en línea es la aceptación de la cacería de trofeos, cuya discusión tiene implicaciones políticas nacionales e internacionales. Usamos una estrategia de métodos mixtos (teoría fundamentada y datos cuantitativos agrupados) para identificar los temas en el debate sobre la cacería de trofeos en Twitter. Analizamos las categorías concurrentes más comunes que describían la postura de las personas con respecto al tema. Identificamos doce categorías y cuatro arquetipos preliminares en contra de la cacería de trofeos (activista, científico, condenatorio y opositor), cuya oposición derivó de diferentes razonamientos morales. Pocos tuits (22) en nuestra muestra de 500 apoyaban la cacería de trofeos, mientras que 350 se oponían a ella. El debate era hostil, pues 7% de los tuits en nuestra muestra estuvieron categorizados como abusivos. Los debates en línea pueden ser improductivos y nuestros descubrimientos pueden ser importantes para los actores que desean participar de forma efectiva en el debate sobre la cacería de trofeos en Twitter. De manera más generalizada, sostenemos que, debido a la creciente influencia de las redes sociales, es importante que las respuestas públicas a los temas polémicos de conservación estén contextualizadas de manera formal para así auxiliar a la comunicación de la evidencia de conservación y para integrar las diferentes perspectivas públicas en la práctica de la conservación.

Testing Association of Previously Implicated Gene Sets and Gene-Networks in Nicotine Exposed Mouse Models with Human Smoking Phenotypes.

INTRODUCTION: Smoking behaviors are partly heritable, yet the genetic and environmental mechanisms underlying smoking phenotypes are not fully understood. Developmental nicotine exposure (DNE) is a significant risk factor for smoking and leads to gene expression changes in mouse models; however, it is unknown whether the same genes whose expression is impacted by DNE are also those underlying smoking genetic liability. We examined whether genes whose expression in D1-type striatal medium spiny neurons due to DNE in the mouse are also associated with human smoking behaviors. METHODS: Specifically, we assessed whether human orthologs of mouse-identified genes, either individually or as a set, were genetically associated with five human smoking traits using MAGMA and S-LDSC while implementing a novel expression-based gene-SNP annotation methodology. RESULTS: We found no strong evidence that these genes sets were more strongly associated with smoking behaviors than the rest of the genome, but ten of these individual genes were significantly associated with three of the five human smoking traits examined (p < 2.5e-6). Three of these genes have not been reported previously and were discovered only when implementing the expression-based annotation. CONCLUSIONS: These results suggest the genes whose expression is impacted by DNE in mice are largely distinct from those contributing to smoking genetic liability in humans. However, examining a single mouse neuronal cell type may be too fine a resolution for comparison, suggesting that experimental manipulation of nicotine consumption, reward, or withdrawal in mice may better capture genes related to the complex genetics of human tobacco use. IMPLICATIONS: Genes whose expression is impacted by DNE in mouse D1-type striatal medium spiny neurons were not found to be, as a whole, more strongly associated with human smoking behaviors than the rest of the genome, though ten individual mouse-identified genes were associated with human smoking traits. This suggests little overlap between the genetic mechanisms impacted by DNE and those influencing heritable liability to smoking phenotypes in humans. Further research is warranted to characterize how developmental nicotine exposure paradigms in mice can be translated to understand nicotine use in humans and their heritable effects on smoking.

From clinical to corporate: opportunities for nurses away from the bedside.

Luke Evans, Education Fellow, UCLPartners, London, meets nurses whose careers have taken them from the NHS to a variety of different roles.

The relationships between perceived mental illness prevalence, mental illness stigma, and attitudes toward help-seeking.

Previous research suggests that, despite the commonality of mental illness in the United States, the majority of U.S. individuals with mental illness do not seek treatment. One important factor that contributes to this lack of treatment utilization is mental illness stigma. Such stigma may result, in part, from many individuals in the U.S. underestimating the prevalence of mental illness. To test whether this is the case, 638 adults from across the U.S. completed measures related to perceived prevalence of mental illness, private stigma, perceived public stigma, and help-seeking. Findings indicated participants significantly underestimated the given-year prevalence rate of mental illness. The perceived given-year prevalence rate was significantly correlated with lower private stigma and more positive attitudes towards help-seeking. Personal stigma significantly predicted attitudes towards help-seeking. Findings also suggested that individuals who have received mental health services have a higher perceived prevalence rate of mental illness, as well as lower levels of personal stigma and more positive attitudes towards help-seeking. These findings support the notion that helping the general public recognize the true prevalence rate of mental illness could reduce personal mental illness stigma and facilitate help-seeking behaviors. However, future experimental studies are needed to test this hypothesis.

The Relationship Between Religiousness/Spirituality and Psychometric Intelligence in the United States.

An inverse relationship between religiousness/spirituality (R/S) and psychometric intelligence (IQ) is well-documented in previous literature. However, the studies that have examined group differences on IQ regarding R/S have limited generalizability. The present study contributed to the literature by evaluating IQ among participants identifying as differentially religious/spiritual (i.e., religious only, spiritual only, both religious and spiritual, or neither religious nor spiritual) and among those classified as either Christian/Catholic, Atheist, or Agnostic. Four hundred and thirty-two participants (M age = 37.9; 36% men) participated online via Amazon's Mechanical Turk as part of a larger study and completed a brief measure of IQ, a scale of religiousness and spirituality, and a demographics questionnaire. Correlations between IQ and self-reported religiousness/spirituality were small and negative (Mean r = -0.17), consistent with previous literature. Multivariate analyses of covariance (MANCOVAs) controlling for age, gender, education, and socioeconomic status (operationalized by estimated annual household income) indicated that IQ scores tended to be lowest (p < 0.001) for "religious only" participants (estimated marginal mean [EMM] = 93.0) and highest for "neither religious nor spiritual" participants (EMM = 103.7). Furthermore, IQ scores were significantly lower (ps < 0.001) for Christian/Catholic participants (EMM = 96.7) compared to both Atheist (EMM = 104.9) and Agnostic participants (EMM = 107.5). Discussion of these findings, relationships to previous theoretical and empirical work, limitations of the present study, and directions for future inquiry are provided.

A 5-Enolpyruvylshikimate 3-Phosphate Synthase Functions as a Transcriptional Repressor in Populus.

Long-lived perennial plants, with distinctive habits of inter-annual growth, defense, and physiology, are of great economic and ecological importance. However, some biological mechanisms resulting from genome duplication and functional divergence of genes in these systems remain poorly studied. Here, we discovered an association between a poplar (Populus trichocarpa) 5-enolpyruvylshikimate 3-phosphate synthase gene (PtrEPSP) and lignin biosynthesis. Functional characterization of PtrEPSP revealed that this isoform possesses a helix-turn-helix motif in the N terminus and can function as a transcriptional repressor that regulates expression of genes in the phenylpropanoid pathway in addition to performing its canonical biosynthesis function in the shikimate pathway. We demonstrated that this isoform can localize in the nucleus and specifically binds to the promoter and represses the expression of a SLEEPER-like transcriptional regulator, which itself specifically binds to the promoter and represses the expression of PtrMYB021 (known as MYB46 in Arabidopsis thaliana), a master regulator of the phenylpropanoid pathway and lignin biosynthesis. Analyses of overexpression and RNAi lines targeting PtrEPSP confirmed the predicted changes in PtrMYB021 expression patterns. These results demonstrate that PtrEPSP in its regulatory form and PtrhAT form a transcriptional hierarchy regulating phenylpropanoid pathway and lignin biosynthesis in Populus.

Whole-Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open-Field Activity.

We conducted whole-genome sequencing of four inbred mouse strains initially selected for high (H1, H2) or low (L1, L2) open-field activity (OFA), and then examined strain distribution patterns for all DNA variants that differed between their BALB/cJ and C57BL/6J parental strains. Next, we assessed genome-wide sharing (3,678,826 variants) both between and within the High and Low Activity strains. Results suggested that about 10% of these DNA variants may be associated with OFA, and clearly demonstrated its polygenic nature. Finally, we conducted bioinformatic analyses of functional genomics data from mouse, rat, and human to refine previously identified quantitative trait loci (QTL) for anxiety-related measures. This combination of sequence analysis and genomic-data integration facilitated refinement of previously intractable QTL findings, and identified possible genes for functional follow-up studies.

Genetic data improves niche model discrimination and alters the direction and magnitude of climate change forecasts.

Ecological niche models (ENMs) have classically operated under the simplifying assumptions that there are no barriers to gene flow, species are genetically homogeneous (i.e., no population-specific local adaptation), and all individuals share the same niche. Yet, these assumptions are violated for most broadly distributed species. Here, we incorporate genetic data from the widespread riparian tree species narrowleaf cottonwood (Populus angustifolia) to examine whether including intraspecific genetic variation can alter model performance and predictions of climate change impacts. We found that (1) P. angustifolia is differentiated into six genetic groups across its range from México to Canada and (2) different populations occupy distinct climate niches representing unique ecotypes. Comparing model discriminatory power, (3) all genetically informed ecological niche models (gENMs) outperformed the standard species-level ENM (3-14% increase in AUC; 1-23% increase in pROC). Furthermore, (4) gENMs predicted large differences among ecotypes in both the direction and magnitude of responses to climate change and (5) revealed evidence of niche divergence, particularly for the Eastern Rocky Mountain ecotype. (6) Models also predicted progressively increasing fragmentation and decreasing overlap between ecotypes. Contact zones are often hotspots of diversity that are critical for supporting species' capacity to respond to present and future climate change, thus predicted reductions in connectivity among ecotypes is of conservation concern. We further examined the generality of our findings by comparing our model developed for a higher elevation Rocky Mountain species with a related desert riparian cottonwood, P. fremontii. Together our results suggest that incorporating intraspecific genetic information can improve model performance by addressing this important source of variance. gENMs bring an evolutionary perspective to niche modeling and provide a truly "adaptive management" approach to support conservation genetic management of species facing global change.

Sexual dimorphism in the dioecious willow Salix purpurea.

PREMISE: The evolution of sex chromosomes is driven by sexual dimorphism, yet it can be challenging to document sexually dimorphic traits in dioecious plant species. At the genetic level, sexual dimorphism can be identified through sequence variation between females and males associated with sexually antagonistic traits and different fitness optima. This study aims to examine sexual dimorphism for 26 traits in three populations of Salix purpurea (a diversity panel and F1 and F2 populations) and determine the effect of the traits on biomass yield, a key trait in Salix bioenergy crops across multiple years, locations, and under manipulated growth conditions. METHODS: Sexual dimorphism was evaluated for morphological, phenological, physiological, and wood composition traits in a diversity panel of unrelated S. purpurea accessions and in full-sib F1 and F2 families produced through controlled cross pollinations and grown in replicated field trials. RESULTS: We observed sexual dimorphism in the timing of development for several traits that were highly predictive of biomass yield across three populations of S. purpurea. Across all populations and years surveyed, males had significantly shallower branching angle. Male plants highly predictive of biomass yield across three populations of S. purpurea also accumulated more nitrogen under fertilizer amendment as measured by SPAD in the diversity panel and had greater susceptibility to the rust fungus Melampsora americana in the F2 family. Allometric modelling of biomass yield showed an effect of sex and of location on the interaction between yield and stem height. CONCLUSIONS: These results provide evidence of sexual dimorphism for certain traits in S. purpurea that may be involved in sex chromosome evolution.

Little Evidence of Modified Genetic Effect of rs16969968 on Heavy Smoking Based on Age of Onset of Smoking.

INTRODUCTION: Tobacco smoking is the leading cause of preventable death globally. Smoking quantity, measured in cigarettes per day, is influenced both by the age of onset of regular smoking (AOS) and by genetic factors, including a strong effect of the nonsynonymous single-nucleotide polymorphism rs16969968. A previous study by Hartz et al. reported an interaction between these two factors, whereby rs16969968 risk allele carriers who started smoking earlier showed increased risk for heavy smoking compared with those who started later. This finding has yet to be replicated in a large, independent sample. METHODS: We performed a preregistered, direct replication attempt of the rs16969968 × AOS interaction on smoking quantity in 128 383 unrelated individuals from the UK Biobank, meta-analyzed across ancestry groups. We fit statistical association models mirroring the original publication as well as formal interaction tests on multiple phenotypic and analytical scales. RESULTS: We replicated the main effects of rs16969968 and AOS on cigarettes per day but failed to replicate the interaction using previous methods. Nominal significance of the rs16969968 × AOS interaction term depended strongly on the scale of analysis and the particular phenotype, as did associations stratified by early/late AOS. No interaction tests passed genome-wide correction (α = 5e-8), and all estimated interaction effect sizes were much smaller in magnitude than previous estimates. CONCLUSIONS: We failed to replicate the strong rs16969968 × AOS interaction effect previously reported. If such gene-moderator interactions influence complex traits, they likely depend on scale of measurement, and current biobanks lack the power to detect significant genome-wide associations given the minute effect sizes expected. IMPLICATIONS: We failed to replicate the strong rs16969968 × AOS interaction effect on smoking quantity previously reported. If such gene-moderator interactions influence complex traits, current biobanks lack the power to detect significant genome-wide associations given the minute effect sizes expected. Furthermore, many potential interaction effects are likely to depend on the scale of measurement employed.

Relationships between estimated autozygosity and complex traits in the UK Biobank.

Inbreeding increases the risk of certain Mendelian disorders in humans but may also reduce fitness through its effects on complex traits and diseases. Such inbreeding depression is thought to occur due to increased homozygosity at causal variants that are recessive with respect to fitness. Until recently it has been difficult to amass large enough sample sizes to investigate the effects of inbreeding depression on complex traits using genome-wide single nucleotide polymorphism (SNP) data in population-based samples. Further, it is difficult to infer causation in analyses that relate degree of inbreeding to complex traits because confounding variables (e.g., education) may influence both the likelihood for parents to outbreed and offspring trait values. The present study used runs of homozygosity in genome-wide SNP data in up to 400,000 individuals in the UK Biobank to estimate the proportion of the autosome that exists in autozygous tracts-stretches of the genome which are identical due to a shared common ancestor. After multiple testing corrections and controlling for possible sociodemographic confounders, we found significant relationships in the predicted direction between estimated autozygosity and three of the 26 traits we investigated: age at first sexual intercourse, fluid intelligence, and forced expiratory volume in 1 second. Our findings corroborate those of several published studies. These results may imply that these traits have been associated with Darwinian fitness over evolutionary time. However, some of the autozygosity-trait relationships were attenuated after controlling for background sociodemographic characteristics, suggesting that alternative explanations for these associations have not been eliminated. Care needs to be taken in the design and interpretation of ROH studies in order to glean reliable information about the genetic architecture and evolutionary history of complex traits.

Convergent Validity and Preliminary Cut-Off Scores for the Anxiety and Depression Subscales of the DASS-21 in US Adolescents.

Although the depression and anxiety subscales (DASS-D and DASS-A) of the 21-item Depression, Anxiety, and Stress Scales are commonly used in adolescents, few studies have investigated the convergent validity of/potential cutoff scores for these subscales in U.S. adolescents. To address these gaps, 306 U.S. adolescents completed the DASS-21, Generalized Anxiety Disorder-7 scale (GAD7), and Center for Epidemiological Studies-Depression Scale (CESD). The DASS-D and CESD were strongly correlated, while the DASS-A and GAD7 were strongly correlated in males and more moderately correlated in females. Using the CESD as reference, DASS-D cutoff scores of four for males and five for females provided the best balance of sensitivity and specificity. When using the GAD7 as reference, DASS-A cutoffs of six for females and five for males appeared best. These findings suggest the DASS-A and DASS-D demonstrate good convergent validity and may be suitable for identifying adolescents who are significantly anxious and/or depressed.

Novel characterization of the multivariate genetic architecture of internalizing psychopathology and alcohol use.

Genetic correlations suggest that the genetic relationship of alcohol use with internalizing psychopathology depends on the measure of alcohol use. Problematic alcohol use (PAU) is positively genetically correlated with internalizing psychopathology, whereas alcohol consumption ranges from not significantly correlated to moderately negatively correlated with internalizing psychopathology. To explore these different genetic relationships of internalizing psychopathology with alcohol use, we performed a multivariate genome-wide association study of four correlated factors (internalizing psychopathology, PAU, quantity of alcohol consumption, and frequency of alcohol consumption) and then assessed genome-wide and local genetic covariance between these factors. We identified 14 significant regions of local, largely positive, genetic covariance between PAU and internalizing psychopathology and 12 regions of significant local genetic covariance (including both positive and negative genetic covariance) between consumption factors and internalizing psychopathology. Partitioned genetic covariance among functional annotations suggested that brain tissues contribute significantly to positive genetic covariance between internalizing psychopathology and PAU but not to the genetic covariance between internalizing psychopathology and quantity or frequency of alcohol consumption. We hypothesize that genome-wide genetic correlations between alcohol use and psychiatric traits may not capture the more complex shared or divergent genetic architectures at the locus or tissue specific level. This study highlights the complexity of genetic architectures of alcohol use and internalizing psychopathology, and the differing shared genetics of internalizing disorders with PAU compared to consumption.

Phenological responses in a sycamore-aphid-parasitoid system and consequences for aphid population dynamics: A 20 year case study.

Species interactions have a spatiotemporal component driven by environmental cues, which if altered by climate change can drive shifts in community dynamics. There is insufficient understanding of the precise time windows during which inter-annual variation in weather drives phenological shifts and the consequences for mismatches between interacting species and resultant population dynamics-particularly for insects. We use a 20 year study on a tri-trophic system: sycamore Acer pseudoplatanus, two associated aphid species Drepanosiphum platanoidis and Periphyllus testudinaceus and their hymenopteran parasitoids. Using a sliding window approach, we assess climatic drivers of phenology in all three trophic levels. We quantify the magnitude of resultant trophic mismatches between aphids and their plant hosts and parasitoids, and then model the impacts of these mismatches, direct weather effects and density dependence on local-scale aphid population dynamics. Warmer temperatures in mid-March to late-April were associated with advanced sycamore budburst, parasitoid attack and (marginally) D. platanoidis emergence. The precise time window during which spring weather advances phenology varies considerably across each species. Crucially, warmer temperatures in late winter delayed the emergence of both aphid species. Seasonal variation in warming rates thus generates marked shifts in the relative timing of spring events across trophic levels and mismatches in the phenology of interacting species. Despite this, we found no evidence that aphid population growth rates were adversely impacted by the magnitude of mismatch with their host plants or parasitoids, or direct impacts of temperature and precipitation. Strong density dependence effects occurred in both aphid species and probably buffered populations, through density-dependent compensation, from adverse impacts of the marked inter-annual climatic variation that occurred during the study period. These findings explain the resilience of aphid populations to climate change and uncover a key mechanism, warmer winter temperatures delaying insect phenology, by which climate change drives asynchronous shifts between interacting species.