On the replication of genetic associations: timing can be everything!

The failure of researchers to replicate genetic-association findings is most commonly attributed to insufficient statistical power, population stratification, or various forms of between-study heterogeneity or environmental influences.(1) Here, we illustrate another potential cause for nonreplications that has so far not received much attention in the literature. We illustrate that the strength of a genetic effect can vary by age, causing "age-varying associations." If not taken into account during the design and the analysis of a study, age-varying genetic associations can cause nonreplication. By using the 100K SNP scan of the Framingham Heart Study, we identified an age-varying association between a SNP in ROBO1 and obesity and hypothesized an age-gene interaction. This finding was followed up in eight independent samples comprising 13,584 individuals. The association was replicated in five of the eight studies, showing an age-dependent relationship (one-sided combined p = 3.92 x 10(-9), combined p value from pediatric cohorts = 2.21 x 10(-8), combined p value from adult cohorts = 0.00422). Furthermore, this study illustrates that it is difficult for cross-sectional study designs to detect age-varying associations. If the specifics of age- or time-varying genetic effects are not considered in the selection of both the follow-up samples and in the statistical analysis, important genetic associations may be missed.     

Propagation Loss of Long-Range Surface Plasmon Polariton Gold Stripe Waveguides in the Thin-Film Limit

Propagation loss experienced by long-range plasmon polaritons in ultrathin gold stripe waveguides embedded in different polymer cladding materials was studied and correlated with atomic-scale characterization of the gold film structure. We identify the main sources of experimentally observed propagation loss which deviates from ideal values in the thin-film limit. Increased loss can be translated to an increased effective thickness of the ultrathin films due to incomplete surface coverage and the presence of diffuse interfaces, both of which depend significantly on the choice of cladding material. The results illustrate the importance of atomic-scale dynamics of metal film formation for the selection of optimum substrate materials for surface plasmon polariton waveguides, resonant transmission structures, and semitransparent electrical contacts.     

A retrospective approach to fractionize variation in body mass of Atlantic cod Gadus morhua

Eggs of a single spawning batch from wild-caught Norwegian Atlantic cod Gadus morhua were hatched and first fed on either natural zooplankton or enriched rotifers Brachionus plicatilis during the larval period. Juvenile G. morhua (initial mass 14·2 g) from the two first-feeding groups were then reared for 3 months under a variety of temperature (10 and 14° C) and salinity (15 and 32) combinations. All fish were individually tagged and microsatellite markers were used in a multiplex to trace the pedigree of all fish and body mass variation analysed according to different environmental and genetic sources. After the termination of the laboratory trial, the fish were transferred to land-based tanks and later to sea pens and reared at ambient conditions for 26 months until they were harvested in March 2009. Growth gain from the larval and juvenile periods was persistent during the 26 months of sea pen ongrowing. The final mass of the zooplankton group was 12% higher compared to the B. plicatilis group. Similarly, rearing under a temperature of 14° C and salinity of 15 during the initial 3 month period during the early juvenile stage resulted in 7-13% larger size at harvesting compared to the other three temperature and salinity combinations. The study indicates that the first-feeding method and temperature and salinity manipulation explain nearly 90% of the body mass variation explained by the model. The genetic effect (measured as body mass variation within the families studied) only accounted for c. 2% during the initial rearing period, whereas it has a large effect on growth variation (30%) during the long-term rearing at ambient conditions. Sex proportion and final maturation did not differ between family groups, and no interaction between sex and family group was seen.     

The Influence of Genetic Drift and Selection on Quantitative Traits in a Plant Pathogenic Fungus

Genetic drift and selection are ubiquitous evolutionary forces acting to shape genetic variation in populations. While their relative importance has been well studied in plants and animals, less is known about their relative importance in fungal pathogens. Because agro-ecosystems are more homogeneous environments than natural ecosystems, stabilizing selection may play a stronger role than genetic drift or diversifying selection in shaping genetic variation among populations of fungal pathogens in agro-ecosystems. We tested this hypothesis by conducting a Q _ST/F _ST analysis using agricultural populations of the barley pathogen Rhynchosporium commune. Population divergence for eight quantitative traits (Q _ST) was compared with divergence at eight neutral microsatellite loci (F _ST) for 126 pathogen strains originating from nine globally distributed field populations to infer the effects of genetic drift and types of selection acting on each trait. Our analyses indicated that five of the eight traits had Q _ST values significantly lower than F _ST, consistent with stabilizing selection, whereas one trait, growth under heat stress (22°C), showed evidence of diversifying selection and local adaptation (Q _ST>F _ST). Estimates of heritability were high for all traits (means ranging between 0.55–0.84), and average heritability across traits was negatively correlated with microsatellite gene diversity. Some trait pairs were genetically correlated and there was significant evidence for a trade-off between spore size and spore number, and between melanization and growth under benign temperature. Our findings indicate that many ecologically and agriculturally important traits are under stabilizing selection in R. commune and that high within-population genetic variation is maintained for these traits.     

Long‐term effects of photoperiod,temperature and their interaction on growth,gill Na+, K+‐ATPase activity,seawater tolerance and plasma growth‐hormone levels in Atlantic salmon Salmo salar

This study was undertaken to examine the long‐term effects of photoperiod, temperature and their interaction on growth, gill Na⁺,K⁺‐ATPase (NKA) activity, seawater tolerance and plasma growth‐hormone levels in Atlantic salmon Salmo salar pre‐smolts and smolts. The fish (mean ± s.e . initial body mass = 15·9 ± 0·4 g) were reared on two photoperiods (continuous light, LL, and simulated natural photoperiod, LDN, 60° 25′ N) and two temperatures (8·3 and 12·7° C) from June to May of the following year. Mean body mass was affected by photoperiod, temperature and their interactions. Both temperature groups on LL developed peak levels in gill NKA activity from October to November, 4–5 months prior to the natural season for the parr–smolt transformation. Fish at 12° C showed peak levels in NKA activity 4–6 weeks before the fish at 8° C. Fish in all four experimental groups showed maximum NKA activity within a similar size range (113–162 g). The present findings further indicate that smoltification in S. salar is to some extent driven by size, and that S. salar will develop smolt characteristics, e.g. a marked increase in NKA activity, within a similar size range. Faster‐growing S. salar will, thus, reach this size threshold at a relatively younger age.     

Habitat- and sex-related differences in a small carnivore’s diet in a competitor-free environment

The alien invasive American mink Neovison vison is fully established in the low species richness and competitor-free environment of Iceland. This study documents the diversity as well as seasonal and sexual variation in the diet of mink in Iceland based on stomach contents. Seasonal changes mainly reflected variation in abundance of migratory birds and wood mice Apodemus sylvaticus. In comparison with mink elsewhere in similar habitats, the mink in Iceland consumed more fish and birds and fewer mammals, which is in accordance with local availability. This reinforces evidence of opportunistic foraging. Females generally ate more fish and fewer birds than males and this might be explained by their smaller body size and possible limitation in catching larger birds. Mink in coastal habitats showed greater sexual differences in diet than mink in riparian habitats, probably reflecting less prey diversity in riparian habitats than coastal ones. This study is an input towards explaining the ecological consequences of sexual size dimorphism and supports the hypothesis that generalist species might be successful invaders due to their capability in utilising new and diverse resources. The mink in Iceland can be regarded as a model for a small-bodied semi-aquatic carnivore away from the confounding effects of inter-specific competition.