The role of adiposity in cardiometabolic traits:a Mendelian randomization analysis

The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Microbial weeds in hypersaline habitats: the enigma of the weed-like Haloferax mediterranei

Heterotrophic prokaryotic communities that inhabit saltern crystallizer ponds are typically dominated by two species, the archaeon Haloquadratum walsbyi and the bacterium Salinibacter ruber, regardless of location. These organisms behave as ‘microbial weeds’ as defined by Cray et al. (Microb Biotechnol 6: 453–492, 2013) that possess the biological traits required to dominate the microbiology of these open habitats. Here, we discuss the enigma of the less abundant Haloferax mediterranei, an archaeon that grows faster than any other, comparable extreme halophile. It has a wide window for salt tolerance, can grow on simple as well as on complex substrates and degrade polymeric substances, has different modes of anaerobic growth, can accumulate storage polymers, produces gas vesicles, and excretes halocins capable of killing other Archaea. Therefore, Hfx. mediterranei is apparently more qualified as a ‘microbial weed’ than Haloquadratum and Salinibacter. However, the former differs because it produces carotenoid pigments only in the lower salinity range and lacks energy-generating retinal-based, light-driven ion pumps such as bacteriorhodopsin and halorhodopsin. We discuss these observations in relation to microbial weed biology in, and the open-habitat ecology of, hypersaline systems.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Expertly validated models and phylogenetically-controlled analysis suggests responses to climate change are related to species traits in the Order Lagomorpha

Climate change during the last five decades has impacted significantly on natural ecosystems and the rate of current climate change is of great concern among conservation biologists. Species Distribution Models (SDMs) have been used widely to project changes in species’ bioclimatic envelopes under future climate scenarios. Here, we aimed to advance this technique by assessing future changes in the bioclimatic envelopes of an entire mammalian order, the Lagomorpha, using a novel framework for model validation based jointly on subjective expert evaluation and objective model evaluation statistics. SDMs were built using climatic, topographical and habitat variables for all 87 lagomorph species under past and current climate scenarios. Expert evaluation and Kappa values were used to validate past and current models and only those deemed ‘modellable’ within our framework were projected under future climate scenarios (58 species). Phylogenetically-controlled regressions were used to test whether species traits correlated with predicted responses to climate change. Climate change is likely to impact more than two-thirds of lagomorph species, with leporids (rabbits, hares and jackrabbits) likely to undertake poleward shifts with little overall change in range extent, whilst pikas are likely to show extreme shifts to higher altitudes associated with marked range declines, including the likely extinction of Kozlov’s Pika (Ochotona koslowi). Smaller-bodied species were more likely to exhibit range contractions and elevational increases, but showing little poleward movement, and fecund species were more likely to shift latitudinally and elevationally. Our results suggest that species traits may be important indicators of future climate change and we believe multi-species approaches, as demonstrated here, are likely to lead to more effective mitigation measures and conservation management. We strongly advocate studies minimising data gaps in our knowledge of the Order, specifically collecting more specimens for biodiversity archives and targeting data deficient geographic regions.

Biogeography, macroecology and species’ traits mediate competitive interactions in the order Lagomorpha

1. In addition to abiotic determinants, biotic factors, including competitive, interspecific interactions, limit species’ distributions. Environmental changes in human disturbance, land use and climate are predicted to have widespread impacts on interactions between species, especially in the order Lagomorpha due to the higher latitudes and more extreme environmental conditions they occupy.
2. We reviewed the published literature on interspecific interactions in the order Lagomorpha, and compared the biogeography, macroecology, phylogeny and traits of species known to interact with those of species with no reported interactions, to investigate how projected future environmental change may affect interactions and potentially alter species’ distributions.
3. Thirty-three lagomorph species have competitive interactions reported in the literature; the majority involve hares (Lepus sp.) or the eastern cottontail rabbit (Sylvilagus floridanus). Key regions for interactions are located between 30-50°N of the Equator, and include eastern Asia (southern Russia on the border of Mongolia) and North America (north western USA).
4. Closely related, large-bodied, similarly sized species occurring in regions of human-modified, typically agricultural landscapes, or at high elevations are significantly more likely to have reported competitive interactions than other lagomorph species.
5. We identify species’ traits associated with competitive interactions, and highlight some potential impacts that future environmental change may have on interspecific interactions. Our approach using bibliometric and biological data is widely applicable, and with relatively straightforward methodologies, can provide insights into interactions between species.
6. Our results have implications for predicting species’ responses to global change, and we advise that capturing, parameterizing and incorporating interspecific interactions into analyses (for example, species distribution modelling) may be more important than suggested by the literature.

Computational cancer biology: education is a natural key to many locks

Background: Oncology is a field that profits tremendously from the genomic data generated by high-throughput technologies, including next-generation sequencing. However, in order to exploit, integrate, visualize and interpret such high-dimensional data efficiently, non-trivial computational and statistical analysis methods are required that need to be developed in a problem-directed manner.

Discussion: For this reason, computational cancer biology aims to fill this gap. Unfortunately, computational cancer biology is not yet fully recognized as a coequal field in oncology, leading to a delay in its maturation and, as an immediate consequence, an under-exploration of high-throughput data for translational research.

Summary: Here we argue that this imbalance, favoring 'wet lab-based activities', will be naturally rectified over time, if the next generation of scientists receives an academic education that provides a fair and competent introduction to computational biology and its manifold capabilities. Furthermore, we discuss a number of local educational provisions that can be implemented on university level to help in facilitating the process of harmonization.

Molecular pedigree reconstruction and estimation of evolutionary parameters in a wild Atlantic salmon river system with incomplete sampling: a power analysis

Background: Pedigree reconstruction using genetic analysis provides a useful means to estimate fundamental population biology parameters relating to population demography, trait heritability and individual fitness when combined with other sources of data. However, there remain limitations to pedigree reconstruction in wild populations, particularly in systems where parent-offspring relationships cannot be directly observed, there is incomplete sampling of individuals, or molecular parentage inference relies on low quality DNA from archived material. While much can still be inferred from incomplete or sparse pedigrees, it is crucial to evaluate the quality and power of available genetic information a priori to testing specific biological hypotheses. Here, we used microsatellite markers to reconstruct a multi-generation pedigree of wild Atlantic salmon (Salmo salar L.) using archived scale samples collected with a total trapping system within a river over a 10 year period. Using a simulation-based approach, we determined the optimal microsatellite marker number for accurate parentage assignment, and evaluated the power of the resulting partial pedigree to investigate important evolutionary and quantitative genetic characteristics of salmon in the system.

Results: We show that at least 20 microsatellites (ave. 12 alleles/locus) are required to maximise parentage assignment and to improve the power to estimate reproductive success and heritability in this study system. We also show that 1.5 fold differences can be detected between groups simulated to have differing reproductive success, and that it is possible to detect moderate heritability values for continuous traits (h(2) similar to 0.40) with more than 80% power when using 28 moderately to highly polymorphic markers.

Conclusion: The methodologies and work flow described provide a robust approach for evaluating archived samples for pedigree-based research, even where only a proportion of the total population is sampled. The results demonstrate the feasibility of pedigree-based studies to address challenging ecological and evolutionary questions in free-living populations, where genealogies can be traced only using molecular tools, and that significant increases in pedigree assignment power can be achieved by using higher numbers of markers.