trait causal relationships
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Cardiometabolic diseases, such as type 2 diabetes and cardiovascular disease, have a high public health burden. Understanding the genetically determined regulation of proteins that are dysregulated in disease can help to dissect the complex biology underpinning them. Here, we perform a protein quantitative trait locus (pQTL) analysis of 248 serum proteins relevant to cardiometabolic processes in 2893 individuals. Meta-analyzing whole-genome sequencing (WGS) data from two Greek cohorts, MANOLIS (n = 1356; 22.5× WGS) and Pomak (n = 1537; 18.4× WGS), we detect 301 independently associated pQTL variants for 170 proteins, including 12 rare variants (minor allele frequency < 1%). We additionally find 15 pQTL variants that are rare in non-Finnish European populations but have drifted up in the frequency in the discovery cohorts here. We identify proteins causally associated with cardiometabolic traits, including Mep1b for high-density lipoprotein (HDL) levels, and describe a knock-out (KO) Mep1b mouse model. Our findings furnish insights into the genetic architecture of the serum proteome, identify new protein-disease relationships and demonstrate the importance of isolated populations in pQTL analysis.
- MeSH
- celogenomová asociační studie MeSH
- diabetes mellitus 2. typu * MeSH
- fenotyp MeSH
- kardiovaskulární nemoci * MeSH
- krevní proteiny genetika MeSH
- myši MeSH
- sekvenování celého genomu MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- krevní proteiny MeSH
The effects of plants on the biosphere, atmosphere and geosphere are key determinants of terrestrial ecosystem functioning. However, despite substantial progress made regarding plant belowground components, we are still only beginning to explore the complex relationships between root traits and functions. Drawing on the literature in plant physiology, ecophysiology, ecology, agronomy and soil science, we reviewed 24 aspects of plant and ecosystem functioning and their relationships with a number of root system traits, including aspects of architecture, physiology, morphology, anatomy, chemistry, biomechanics and biotic interactions. Based on this assessment, we critically evaluated the current strengths and gaps in our knowledge, and identify future research challenges in the field of root ecology. Most importantly, we found that belowground traits with the broadest importance in plant and ecosystem functioning are not those most commonly measured. Also, the estimation of trait relative importance for functioning requires us to consider a more comprehensive range of functionally relevant traits from a diverse range of species, across environments and over time series. We also advocate that establishing causal hierarchical links among root traits will provide a hypothesis-based framework to identify the most parsimonious sets of traits with the strongest links on functions, and to link genotypes to plant and ecosystem functioning.
- Klíčová slova
- belowground ecology, ecosystem properties and processes, environmental gradients, plant functions, root traits, spatial and temporal scales, trait causal relationships, trait covariation,
- MeSH
- atmosféra MeSH
- ekologie MeSH
- ekosystém * MeSH
- fenotyp MeSH
- rostliny * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Neurogenesis in the adult hippocampus contributes to learning and memory in the healthy brain but is dysregulated in metabolic and neurodegenerative diseases. The molecular relationships between neural stem cell activity, adult neurogenesis, and global metabolism are largely unknown. Here we applied unbiased systems genetics methods to quantify genetic covariation among adult neurogenesis and metabolic phenotypes in peripheral tissues of a genetically diverse family of rat strains, derived from a cross between the spontaneously hypertensive (SHR/OlaIpcv) strain and Brown Norway (BN-Lx/Cub). The HXB/BXH family is a very well established model to dissect genetic variants that modulate metabolic and cardiovascular diseases and we have accumulated deep phenome and transcriptome data in a FAIR-compliant resource for systematic and integrative analyses. Here we measured rates of precursor cell proliferation, survival of new neurons, and gene expression in the hippocampus of the entire HXB/BXH family, including both parents. These data were combined with published metabolic phenotypes to detect a neurometabolic quantitative trait locus (QTL) for serum glucose and neuronal survival on Chromosome 16: 62.1-66.3 Mb. We subsequently fine-mapped the key phenotype to a locus that includes the Telo2-interacting protein 2 gene (Tti2)-a chaperone that modulates the activity and stability of PIKK kinases. To verify the hypothesis that differences in neurogenesis and glucose levels are caused by a polymorphism in Tti2, we generated a targeted frameshift mutation on the SHR/OlaIpcv background. Heterozygous SHR-Tti2+/- mutants had lower rates of hippocampal neurogenesis and hallmarks of dysglycemia compared to wild-type littermates. Our findings highlight Tti2 as a causal genetic link between glucose metabolism and structural brain plasticity. In humans, more than 800 genomic variants are linked to TTI2 expression, seven of which have associations to protein and blood stem cell factor concentrations, blood pressure and frontotemporal dementia.
- MeSH
- fenotyp MeSH
- glukosa * genetika metabolismus MeSH
- hipokampus metabolismus MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- neurogeneze * genetika MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- glukosa * MeSH
- Tti2 protein, rat MeSH Prohlížeč
Interspecific variation in body size is one of the most popular topics in comparative studies. Despite recent advances, little is known about the patterns and processes behind the evolution of body size in insects. Here, we used a robust data set comprising all geometrid moth species occurring in Northern Europe to examine the evolutionary associations involving body size and several life-history traits under an explicitly phylogenetic framework. We provided new insights into the interactive effects of life-history traits on body size and evidence of correlated evolution. We further established the sequence of trait evolution linking body size with the life-history traits correlated with it. We found that most (but not all) of the studied life-history traits, to some extent, influenced interspecific variation in body size, but interactive effects were uncommon. Both bi- and multivariate phylogenetic analyses indicated that larger species tend to be nocturnal flyers, overwinter in the larval stage, feed on the foliage of trees rather than herbs, and have a generalist feeding behaviour. We found evidence of correlated evolution involving body size with overwintering stage, host-plant growth form, and dietary specialization. The examination of evolutionary transitions within the correlated evolution models signalled that overwintering as larvae commonly preceded the evolution of large sizes, as did feeding on tree foliage and the generalist feeding behaviour. By showing that both body size and all life-history traits correlated with it evolve at very slow rates, we caution against uncritical attempts to propose causal explanations for respective associations based on contemporary ecological settings.
- Klíčová slova
- body size, evolution, evolutionary ecology, insects, macroevolution,
- MeSH
- biologická evoluce * MeSH
- fylogeneze * MeSH
- můry * fyziologie růst a vývoj genetika anatomie a histologie MeSH
- stravovací zvyklosti MeSH
- velikost těla * MeSH
- zvířata MeSH
- zvláštnosti životní historie MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
PREMISE: Increases in genome size in plants-often associated with larger, low-density stomata and greater water-use efficiency (WUE)-could affect plant ecophysiological and hydraulic function. Variation in plant genome size is often due to polyploidy, having occurred repeatedly in the austral sedge genus Schoenus in the Cape Floristic Region (CFR), while species in the other major schoenoid genus in the region, Tetraria, have smaller genomes. Comparing these genera is useful as they co-occur at the landscape level, under broadly similar bioclimatic conditions. We hypothesized that CFR Schoenus have greater WUE, with lower maximum stomatal conductance (gwmax) imposed by larger, less-dense stomata. METHODS: We investigated relationships between genome size and stomatal parameters in a phylogenetic context, reconstructing a phylogeny of CFR-occurring Schoeneae (Cyperaceae). Species' stomatal and functional traits were measured from field-collected and herbarium specimens. Carbon stable isotopes were used as an index of WUE. Genome size was derived from flow-cytometric measurements of leafy shoots. RESULTS: Evolutionary regressions demonstrated that stomatal size and density covary with genome size, positively and negatively, respectively, with genome size explaining 72-75% of the variation in stomatal size. Larger-genomed species had lower gwmax and C:N ratios, particularly in culms. CONCLUSIONS: We interpret differences in vegetative physiology between the genera as evidence of more-conservative strategies in CFR Schoenus compared to the more-acquisitive Tetraria. Because Schoenus have smaller, reduced leaves, they likely rely more on culm photosynthesis than Tetraria. Across the CFR Schoeneae, ecophysiology correlates with genome size, but confounding sources of trait variation limit inferences about causal relationships between traits.
- Klíčová slova
- Cape Floristic Region, Cyperaceae, functional traits, fynbos, genome size, polyploidy, stomatal size, water‐use efficiency,
- MeSH
- délka genomu * MeSH
- fylogeneze * MeSH
- genom rostlinný * MeSH
- listy rostlin fyziologie genetika anatomie a histologie MeSH
- průduchy rostlin * fyziologie genetika MeSH
- šáchorovité genetika fyziologie MeSH
- voda fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- voda MeSH
BACKGROUND: In the European Longitudinal Study of Pregnancy and Childhood (ELSPAC), the pediatric observation of the cohort of 6100 7-year-old children described 4.4% of them as having conduct disorders. METHODS AND RESULTS: The predominant markers such as strong negativism, aggressivity, attention deficit, non-adequate reactions, hyperactivity, disorders of psychomotoric development, school maturation delay, poorer school results and social adaptation described children behavioral problems. The first signs of conduct disorders were often discovered already at the 18th month and the 3rd year of children's age. The acceptance of standardized criteria of possible conduct disorders in the routine pediatric practice, and the special psychologic and/or psychiatric care for children with the confirmed diagnosis should be recommended as soon as in their toddler age. CONCLUSIONS: Possible causal associations between prenatal exposure to nicotine and conduct disorders in childhood are another strong reason for the primary prevention and smoking cessation in antenatal clinics.
- MeSH
- kojenec MeSH
- kouření škodlivé účinky MeSH
- lidé MeSH
- porucha chování diagnóza etiologie psychologie MeSH
- předškolní dítě MeSH
- těhotenství MeSH
- vztahy mezi matkou a dítětem MeSH
- zpožděný efekt prenatální expozice MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
We have attempted to review the majority, if not all, of the available literature concerned with the Type A behavior pattern. The data indicate that the concept of TABP has construct validity and that it does not reflect the distinguishing characteristics of personality traits or psychopathology that are measured by standard psychometric inventories. They support the belief that TABP is an interplay of certain personality attributes and the environmental milieu. This behavior pattern is found to have a causal association with the prevalence and incidence of coronary heart disease and the severity of coronary atherosclerosis in both sexes and predictive strength that is equivalent to the standard risk factors for CHD. The concept of TABP and its relevance for CHD are shown to have cross-cultural validity and to have specificity for CHD in a relationship that has a biological gradient of pathogenecity. TABP can be assessed with substantial replicability and probably can be quantified. The National Heart, Lung, and Blood Institute recently assembled a review panel of more than 50 eminent scientists representing a variety of biomedical and behavioral specialties in order to critically examine the evidence for the association between TABP and CHD. In the opening paragraph of the panel's final report, it was stated that "The Review Panel accepts the available body of scientific evidence as demonstrating that Type A behavior (as defined by the structured interview, JAS, and Framingham scale) is associated with an increased risk of clinically apparent CHD in employed, middle-aged U.S. citizens. This increased risk is over and above that imposed by age, systolic blood pressure, serum cholesterol, and smoking and appears to be of the same order of magnitude as the relative risk associated with any of these factors" (402).
- MeSH
- chování * MeSH
- emoce fyziologie MeSH
- hyperlipidemie patofyziologie MeSH
- katecholaminy metabolismus MeSH
- koronární nemoc etiologie genetika prevence a kontrola MeSH
- lidé MeSH
- osobnost * MeSH
- psychický stres etiologie patofyziologie MeSH
- riziko MeSH
- socioekonomické faktory MeSH
- systém hypofýza - nadledviny patofyziologie MeSH
- systém hypotalamus-hypofýza patofyziologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- katecholaminy MeSH
Genetic data has become an essential part of ecological studies, because the analyses of diversity within and among natural populations may grant access to previously overlooked ecological and evolutionary causalities, especially among cryptic species. Here, we present an example of how phylogenetic analysis of molecular data obtained within a DNA barcoding study, in combination with morphological and ecological data from the field and laboratory experiments, unraveled a striking predator-prey interaction between aquatic organisms. The "crown of thorns," a conspicuous morphological feature among water fleas of the Daphnia atkinsoni species complex (Crustacea: Cladocera), is considered to represent a species-specific trait. However, our study, initiated by the analysis of sequence variation in 2 mitochondrial genes, shows that this feature is phenotypically plastic and is induced by chemical cues released by Triops cancriformis, the tadpole shrimp (Notostraca). The trait acts as an effective antipredator defense, and is found in several Daphnia lineages coexisting with notostracans. These facts suggest that the "crown of thorns" evolved in coexistence with this ancient predator group.
- MeSH
- anatomické modely MeSH
- biologická evoluce MeSH
- biologické modely MeSH
- buněčný rodokmen MeSH
- Cladocera MeSH
- Daphnia anatomie a histologie metabolismus fyziologie MeSH
- ekologie MeSH
- fenotyp MeSH
- fylogeneze MeSH
- lidé MeSH
- mitochondriální DNA metabolismus MeSH
- potravní řetězec MeSH
- predátorské chování MeSH
- respirační komplex IV metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- mitochondriální DNA MeSH
- respirační komplex IV MeSH
Parents affect offspring fitness by propagule size and quality, selection of oviposition site, quality of incubation, feeding of dependent young, and their defence against predators and parasites. Despite many case studies on each of these topics, this knowledge has not been rigorously integrated into individual parental care traits for any taxon. Consequently, we lack a comprehensive, quantitative assessment of how parental care modifies offspring phenotypes. This meta-analysis of 283 studies with 1805 correlations between egg size and offspring quality in birds is intended to fill this gap. The large sample size enabled testing of how the magnitude of the relationship between egg size and offspring quality depends on a number of variables. Egg size was positively related to nearly all studied offspring traits across all stages of the offspring life cycle. Not surprisingly, the relationship was strongest at hatching but persisted until the post-fledging stage. Morphological traits were the most closely related to egg size but significant relationships were also found with hatching success, chick survival, and growth rate. Non-significant effect sizes were found for egg fertility, chick immunity, behaviour, and life-history or sexual traits. Effect size did not depend on whether chicks were raised by their natural parents or were cross-fostered to other territories. Effect size did not depend on species-specific traits such as developmental mode, clutch size, and relative size of the egg, but was larger if tested in captive compared to wild populations and between rather than within broods. In sum, published studies support the view that egg size affects juvenile survival. There are very few studies that tested the relationship between egg size and the fecundity component of offspring fitness, and no studies on offspring survival as adults or on global fitness. More data are also needed for the relationships between egg size and offspring behavioural and physiological traits. It remains to be established whether the relationship between egg size and offspring performance depends on the quality of the offspring environment. Positive effect sizes found in this study are likely to be driven by a causal effect of egg size on offspring quality. However, more studies that control for potential confounding effects of parental post-hatching care, genes, and egg composition are needed to establish firmly this causal link.
- MeSH
- dlouhověkost fyziologie MeSH
- genetická zdatnost MeSH
- ovum cytologie fyziologie MeSH
- ptáci fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Declines in European bird populations are reported for decades but the direct effect of major anthropogenic pressures on such declines remains unquantified. Causal relationships between pressures and bird population responses are difficult to identify as pressures interact at different spatial scales and responses vary among species. Here, we uncover direct relationships between population time-series of 170 common bird species, monitored at more than 20,000 sites in 28 European countries, over 37 y, and four widespread anthropogenic pressures: agricultural intensification, change in forest cover, urbanisation and temperature change over the last decades. We quantify the influence of each pressure on population time-series and its importance relative to other pressures, and we identify traits of most affected species. We find that agricultural intensification, in particular pesticides and fertiliser use, is the main pressure for most bird population declines, especially for invertebrate feeders. Responses to changes in forest cover, urbanisation and temperature are more species-specific. Specifically, forest cover is associated with a positive effect and growing urbanisation with a negative effect on population dynamics, while temperature change has an effect on the dynamics of a large number of bird populations, the magnitude and direction of which depend on species' thermal preferences. Our results not only confirm the pervasive and strong effects of anthropogenic pressures on common breeding birds, but quantify the relative strength of these effects stressing the urgent need for transformative changes in the way of inhabiting the world in European countries, if bird populations shall have a chance of recovering.
- Klíčová slova
- agriculture intensification, anthropogenic pressures, bird conservation, large-scale analysis,
- MeSH
- biodiverzita MeSH
- ekosystém MeSH
- farmy MeSH
- lesy * MeSH
- populační dynamika MeSH
- ptáci fyziologie MeSH
- zachování přírodních zdrojů MeSH
- zemědělství * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH