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Caregivers are often encouraged to praise children to reduce externalizing behavior. Although several theoretical perspectives suggest that praise works (e.g., praise reinforces positive behavior), others suggest it may not (e.g., children dismiss praise or experience it as controlling). This longitudinal-observational study examined whether (a) caregivers' praise and children's externalizing behavior were related; (b) an evidence-based parenting program increased caregivers' praise; (c) and increasing praise reduced children's externalizing behavior. Participants (387 caregiver-child dyads) were randomly assigned to a 14-session parenting program (aiming to improve parenting behavior, partly via praise) or a control group. Children (aged 4-8 years, 45% girls) scored at or above the 75th percentile on externalizing behavior problems. Caregivers (91% Caucasian, 85% born in the Netherlands, 50.5% highly educated) were mostly mothers (91%). At baseline, postintervention, and follow-up, we assessed caregivers' labeled and unlabeled praise via in-home observations, and children's externalizing behavior via caregiver-reports and observations. At baseline, caregivers' unlabeled praise was related to more (rather than less) externalizing behavior. The parenting program successfully increased praise and reduced caregiver-reported (but not observed) externalizing behavior; importantly, however, praise did not mediate the program's effect on caregiver-reported externalizing behavior. Although the program did not directly reduce observed externalizing behavior, it did so indirectly via labeled praise. Our results suggest that, although praise and externalizing child behavior are related, praise may not be a key mechanism underlying the effects of the parenting program. If praise has beneficial effects on children's externalizing behavior, these effects are probably limited to labeled praise. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective:Gene–environment (GxE) interactions may comprise an important part of the aetiology of depression, and childhood maltreatment (CM), a significant stressor, has consistently been linked to depression. Hence, in this systematic review, we aimed to investigate the interaction between hypothalamus–pituitary–adrenal axis (HPA-axis) genes and CM in depression.Methods:We conducted a literature search using the Pubmed, Embase, and PsychINFO databases in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We included studies investigating GxE interactions between HPA-axis genes [Angiotensin Converting Enzyme (ACE), Arginine Vasopressin (AVP), Corticotrophin Releasing Hormone (CRH), Corticotrophin Releasing Hormone Receptor 1 (CRHR1), Corticotrophin Releasing Hormone Receptor 2 (CRHR2), FK506 binding protein (FKBP5), Nuclear Receptor subfamily 3 group C member 1 (NR3C1), Nuclear Receptor subfamily 3 group C member 2 (NR3C2)] and CM in depression.Results:The literature search identified 159 potentially relevant studies. Following screening, 138 of these were excluded. Thus, 21 studies, investigating a total of 51 single nucleotide polymorphisms, were included in the final study. The most prevalent genes in the current study were CRHR1 and FKBP5. Significant GxE interactions were reported in seven of eight studies for CRHR1:rs110402 and CM, and in five of eight studies for FKBP5:rs1360780 and CM. In summary, our results suggest possible GxE interactions between CRHR1, FKBP5, NR3C1, and NR3C2 and CM, respectively. For the remaining genes, no relevant literature emerged.Conclusions:We find that genetic variation in four HPA-axis genes may influence the effects of CM in depression.

Current organic pig-breeding programs use pigs from conventional breeding populations. However, there are considerable differences between conventional and organic production systems. This simulation study aims to evaluate how the organic pig sector could benefit from having an independent breeding program. Two organic pig-breeding programs were simulated: one used sires from a conventional breeding population (conventional sires), and the other used sires from an organic breeding population (organic sires). For maintaining the breeding population, the conventional population used a conventional breeding goal, whereas the organic population used an organic breeding goal. Four breeding goals were simulated: one conventional breeding goal, and three organic breeding goals. When conventional sires were used, genetic gain in the organic population followed the conventional breeding goal, even when an organic breeding goal was used to select conventional sires. When organic sires were used, genetic gain followed the organic breeding goal. From an economic point of view, using conventional sires for breeding organic pigs is best, but only if there are no genotype-by-environment interactions. However, these results show that from a biological standpoint, using conventional sires biologically adapts organic pigs for a conventional production system.

Environmental heterogeneity is a major driver of plant-microbiome assembly, but the specific climate and soil conditions that are involved remain poorly understood. To better understand plant microbiome formation, we examined the bacteria and fungi that colonize wild strawberry (Fragaria vesca) plants in North American and European populations. Using transects as replicates, we found strong overlap among the environmental conditions that best predict the overall similarity and richness of the plant microbiome, including soil nutrients that replicate across continents. Temperature is also among the main predictors of diversity for both bacteria and fungi in both the leaf and, unexpectedly, the root microbiome. Our results indicate that a small number of environmental factors, and their interactions, consistently contribute to plant microbiome formation, which has implications for predicting the contributions of microbes to plant productivity in ever-changing environments. Keywords: Fragaria vesca; environment-by-environment interactions; phyllosphere; rhizosphere; soil microbiota.

The first nine months from conception to birth involves greater changes than at any other time in life, affecting organogenesis, endocrine, metabolic and immune programming. It has led to the concept that the “first 1000 days” from conception to the second birthday are critical in establishing long term health or susceptibility to disease. Immune ontogeny is predominantly complete within that time and is influenced by the maternal genome, health, diet and environment pre-conception and during pregnancy and lactation. Components of the immunological protection of the pregnancy is the generation of Th-2 and T-regulatory cytokines with the consequence that neonatal adaptive responses are also biased towards Th-2 (allergy promoting) and T-regulatory (tolerance promoting) responses. Normally after birth Th-1 activity increases while Th-2 down-regulates and the evolving normal human microbiome likely plays a key role. This in turn will have been affected by maternal health, diet, exposure to antibiotics, mode of delivery, and breast or cow milk formula feeding. Complex gene/environment interactions affect outcomes. Many individual nutrients affect immune mechanisms and variations in levels have been associated with susceptibility to allergic disease. However, intervention trials employing single nutrient supplementation to prevent allergic disease have not achieved the expected outcomes suggested by observational studies. Investigation of overall dietary practices including fresh fruit and vegetables, fish, olive oil, lower meat intake and home cooked foods as seen in the Mediterranean and other healthy diets have been associated with reduced prevalence of allergic disease. This suggests that the “soup” of overall nutrition is more important than individual nutrients and requires further investigation both during pregnancy and after the infant has been weaned. Amongst all the potential factors affecting allergy outcomes, modification of maternal and infant nutrition and the microbiome are easier to employ than changing other aspects of the environment but require large controlled trials before recommending changes to current practice.

Background Prenatal alcohol exposure (PAE) is perhaps the most common environmental cause of human birth defects. These exposures cause a range of structural and neurological defects, including facial dysmorphologies, collectively known as fetal alcohol spectrum disorders (FASD). While PAE causes FASD, phenotypic outcomes vary widely. It is thought that multifactorial genetic and environmental interactions modify the effects of PAE. However, little is known of the nature of these modifiers. Disruption of the Hedgehog (Hh) signaling pathway has been suggested as a modifier of ethanol teratogenicity. In addition to regulating the morphogenesis of craniofacial tissues commonly disrupted in FASD, a core member of the Hh pathway, Smoothened, is susceptible to modulation by structurally diverse chemicals. These include environmentally prevalent teratogens like piperonyl butoxide (PBO), a synergist found in thousands of pesticide formulations. Methods Here, we characterize multifactorial genetic and environmental interactions using a zebrafish model of craniofacial development. Results We show that loss of a single allele of shha sensitized embryos to both alcohol‐ and PBO‐induced facial defects. Co‐exposure of PBO and alcohol synergized to cause more frequent and severe defects. The effects of this co‐exposure were even more profound in the genetically susceptible shha heterozygotes. Conclusions Together, these findings shed light on the multifactorial basis of alcohol‐induced craniofacial defects. In addition to further implicating genetic disruption of the Hh pathway in alcohol teratogenicity, our findings suggest that co‐exposure to environmental chemicals that perturb Hh signaling may be important variables in FASD and related craniofacial disorders., Prenatal alcohol exposure is a major cause of craniofacial birth defects in humans, but outcomes vary widely. Using zebrafish, we tested the hypothesis that genetic predisposition or co‐exposure to additional environmental toxicants can interact with alcohol to worsen craniofacial defects. We identified synergistic interactions between three factors: alcohol, the common pesticide synergist and recently identified Hedgehog pathway inhibitor piperonyl butoxide (PBO), and mutations in the Hedgehog pathway. Together, this work demonstrates multifactorial interactions can exacerbate alcohol‐induced craniofacial defects.

Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking.Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia.Results: We identified an interaction (beta(int) = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect.Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.

PURPOSE: Whilst childhood trauma (CT) is a known risk factor across the spectrum of psychosis expression, little is known about possible interplay with genetic liability. METHODS: The TwinssCan Study collected data in general population twins, focussing on expression of psychosis at the level of subthreshold psychotic experiences. A multilevel mixed-effects linear regression analysis was performed including 745 subjects to assess the interaction between genetic liability and CT. The Symptom Checklist-90 (SCL-90-R) score of the co-twin was used as an indirect measure of genetic liability to psychopathology, while the Childhood Trauma Questionnaire Short-Form (CTQ-SF) was used to assess CT in the domains of physical, emotional and sexual abuse, as well as physical and emotional neglect. The Community Assessment of Psychic Experience (CAPE) questionnaire was used to phenotypically characterize psychosis expression. RESULTS: In the model using the CAPE total score, the interaction between CT and genetic liability was close to statistical significance (χ2 = 5.6, df = 2, p = 0.06). Analyses of CAPE subscales revealed a significant interaction between CT and genetic liability (χ2 = 8.8, df = 2, p = 0.012) for the CAPE-negative symptoms subscale, but not for the other two subscales (i.e. positive and depressive). CONCLUSION: The results suggest that the impact of CT on subthreshold expression of psychosis, particularly in the negative subdomain, may be larger in the co-presence of significant genetic liability for psychopathology. ispartof: SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY vol:54 issue:9 pages:1045-1054 ispartof: location:Germany status: published

Plant height (PH) is one of the most important agronomic traits of rice, as it directly affects the lodging resistance and the high yield potential. Meanwhile, PH is often constrained by water supply over the entire growth period. In this study, a recombinant inbred line (RIL) derived from Xiaobaijingzi and Kongyu 131 strains grown under drought stress and with normal irrigation over 2 yr (2013 and 2014), respectively (regarded as four environments), was used to dissect the genetic basis of PH by developmental dynamics QTL analysis combined with QTL×environment interactions. QTLs with net effects excluding the accumulated effects were detected to explore the relationship between gene×gene interactions and gene×environment interactions in specific growth period. A total of 26 additive QTLs (A-QTLs) and 37 epistatic QTLs (E-QTLs) associated with PH were detected by unconditional and conditional mapping over seven growth periods. qPH-2-3, qPH-4-3, qPH-6-1, qPH-7-1, and qPH-12-5 could be detected by both unconditional and conditional analyses. qPH-4-3 and qPH-7-5 were detected in four stages (periods) to be sequentially expressed QTLs controlling PH continuous variation. QTLs with additive effects (A-QTLs) were mostly expressed in the period S3|S2 (the time interval from stages 2 to 3), and QTL×environment interactions performed actively in the first three stages (periods) which could be an important developmental period for rice to undergo external morphogenesis during drought stress. Several QTLs showed high adaptability for drought stress and many QTLs were closely related to the environments such as qPH-3-5, qPH-2-2 and qPH-6-1. 72.5% of the QTLs with a and aa effects detected by conditional analysis were under drought stress, and the PVE of QTLs detected by conditional analysis under drought stress were also much higher than that under normal irrigation. We infer that environments would influence the detection results and sequential expression of genes was highly influenced by environments as well. Many QTLs (qPH-1-2, qPH-3-5, qPH-4-1, qPH-2-3) coincident with previously identified drought resistance genes. The result of this study is helpful to elucidating the genetic mechanism and regulatory network underlying the development of PH in rice and providing references to marker assisted selection.

The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia.

Understanding processes maintaining variation in pathogen life-history traits is a key challenge in disease biology, and of importance for predicting when and where risks of disease emergence are highest. Pathogens are expected to encounter tremendous levels of variation in their environment - both abiotic and biotic - and this variation may promote maintenance of variation in pathogen populations through space and time. Here, we measure life-history traits of an obligate fungal pathogen at both asexual and sexual stages under both single infection and coinfection along a temperature gradient. We find that temperature had a significant effect on all measured life-history traits while coinfection only had a significant effect on the number of sexual resting structures produced. The effect of temperature on life-history traits was both direct as well as mediated through a genotype-by-temperature interaction. We conclude that pathogen life-history traits vary in their sensitivity to abiotic and biotic variation in the environment.

Recent research in psychiatric genetics has led to a move away from simple diathesis-stress models to more complex models of psychopathology incorporating a focus on gene-environment interactions and epigenetics. Our increased understanding of the way biology encodes the impact of life events on organisms has also generated more sophisticated theoretical models concerning the molecular processes at the interface between "nature" and "nurture." There is also increasing consensus that psychotherapy entails a specific type of learning in the context of an emotional relationship (i.e., the therapeutic relationship) that may also lead to epigenetic modifications across different therapeutic treatment modalities. This paper provides a systematic review of this emerging body of research. It is concluded that, although the evidence is still limited at this stage, extant research does indeed suggest that psychotherapy may be associated with epigenetic changes. Furthermore, it is argued that epigenetic studies may play a key role in the identification of biomarkers implicated in vulnerability for psychopathology, and thus may improve diagnosis and open up future research opportunities regarding the mechanism of action of psychotropic drugs as well as psychotherapy. We review evidence suggesting there may be important individual differences in susceptibility to environmental input, including psychotherapy. In addition, given that there is increasing evidence for the transgenerational transmission of epigenetic modifications in animals and humans exposed to trauma and adversity, epigenetic changes produced by psychotherapy may also potentially be passed on to the next generation, which opens up new perspective for prevention science. We conclude this paper stressing the limitations of current research and by proposing a set of recommendations for future research in this area. ispartof: FRONTIERS IN GENETICS vol:9 ispartof: location:Switzerland status: published

The relative importance of bottom‐up versus top‐down control of population dynamics has been the focus of much debate. In infectious disease biology, research is typically focused on the bottom‐up process of host resistance, wherein the direction of control flows from the lower to the higher trophic level to impact on pathogen population size and epidemiology. However, the importance of top‐down control by a pathogen's natural enemies has been mostly overlooked.Here, we explore the effects of, and interaction between, host genotype (i.e., genetic susceptibility to pathogen infection) and infection by a hyperparasitic fungus, Ampelomyces spp., on the establishment and early epidemic growth and transmission of a powdery mildew plant pathogen (Podosphaera plantaginis). We used a semi‐natural field experiment to contrast the impacts of hyperparasite infection, host‐plant resistance and spatial structure to reveal the key factors that determine pathogen spread. We then used a laboratory‐based inoculation approach to test whether the field experiment results hold across multiple pathogen–host genetic combinations and to explore hyperparasite effects on the pathogen's later life‐history stages.We found that hyperparasite infection had a negligible effect on within‐host infection development and between‐host spread of the pathogen during the onset of epidemics. In contrast, host‐plant resistance was the major determinant of whether plants became infected, and host genotype and proximity to an infection source determined infection severity.Our laboratory study showed that, while the interaction between host and pathogen genotypes was the key determinant of infection outcome, hyperparasitism did, on average, reduce the severity of infection. Moreover, hyperparasite infection negatively influenced the production of the pathogen's overwintering structures. Synthesis and applications. Our results suggest that bottom‐up host resistance affects pathogen spread, but top‐down control of powdery mildew pathogens is likely more effective against later life‐history stages. Further, while hyperparasitism in this system can reduce early pathogen growth under stable laboratory conditions, this effect is not detectable in a semi‐natural environment. Considering the effects of hyperparasites at multiple points in pathogen's life history will be important when considering hyperparasite‐derived biocontrol measures in other natural and agricultural systems., Our results suggest that bottom‐up host resistance affects pathogen spread, but top‐down control of powdery mildew pathogens is likely more effective against later life‐history stages. Further, while hyperparasitism in this system can reduce early pathogen growth under stable laboratory conditions, this effect is not detectable in a semi‐natural environment. Considering the effects of hyperparasites at multiple points in pathogen's life history will be important when considering hyperparasite‐derived biocontrol measures in other natural and agricultural systems.

To improve genetic gain of breeding programs for village poultry production, breeding schemes with observations obtained in village production systems using individual (VIO) and group recording (VGO) were examined under different levels of genotype-by-environment-interactions (GxE). GxE was modeled by varying the correlation between traits measured in the breeding station and village environments for bodyweight (r g_BW ) and egg production (r g_EP ). Relative and absolute genetic gains obtained from VIO and VGO were used for comparison between the schemes. Results showed that village observations significantly improved genetic gains compared to the scheme without birds tested in the village. The improvement was only slightly larger with individual observations than with group observations. Higher r g_BW and r g_EP led to lower relative genetic gain, but a higher absolute gain of VIO and VGO. It is recommended to apply a breeding scheme using group recording of village performance when strong GxE in breeding for village poultry is expected.

Indirect genetic effects (IGEs) are heritable effects of an individual on phenotypic values of others, and may result from social interactions. We determined the behavioural consequences of selection for IGEs for growth (IGEg) in pigs in a G × E treatment design. Pigs (n = 480) were selected for high versus low IGEg with a contrast of 14 g average daily gain and were housed in either barren or straw-enriched pens (n = 80). High IGEg pigs showed from 8 to 23 weeks age 40 % less aggressive biting (P = 0.006), 27 % less ear biting (P = 0.03), and 40 % less biting on enrichment material (P = 0.005). High IGEg pigs had a lower tail damage score (high 2.0; low 2.2; P = 0.004), and consumed 30 % less jute sacks (P = 0.002). Selection on high IGEg reduced biting behaviours additive to the, generally much larger, effects of straw-bedding (P

BACKGROUND: Most gene-environment interaction studies (G × E) have focused on single candidate genes. This approach is criticized for its expectations of large effect sizes and occurrence of spurious results. We describe an approach that accounts for the polygenic nature of most psychiatric phenotypes and reduces the risk of false-positive findings. We apply this method focusing on the role of perceived parental support, psychological control, and harsh punishment in depressive symptoms in adolescence. METHODS: Analyses were conducted on 982 adolescents of Caucasian origin (Mage (SD) = 13.78 (.94) years) genotyped for 4,947 SNPs in 263 genes, selected based on a literature survey. The Leuven Adolescent Perceived Parenting Scale (LAPPS) and the Parental Behavior Scale (PBS) were used to assess perceived parental psychological control, harsh punishment, and support. The Center for Epidemiologic Studies Depression Scale (CES-D) was the outcome. We used gene-based testing taking into account linkage disequilibrium to identify genes containing SNPs exhibiting an interaction with environmental factors yielding a p-value per single gene. Significant results at the corrected p-value of p

Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. Results: We identified an interaction (βint = −0.036, 95% confidence interval, −0.040 to −0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.

Exposure to lead even at low levels correlates with attention-deficit/hyperactivity disorder (ADHD). However, lead-contaminated environments are often contaminated with other heavy metals that could exacerbate lead-induced ADHD. We conducted this study to evaluate the relationship between multiple heavy metals and child behaviors, and the involvement of S100 calcium-binding protein beta (S100 beta) expression in child ADHD in Guiyu, an internationally-known e-waste contaminated recycling town. Two hundred and forty kindergarten children, 3- to 7-years of age, who lived in Guiyu, were recruited for this study. Child behavioral assessment was derived from parent and teacher ratings. Serum S100 beta was assayed by an enzyme-linked immunosorbent assay (ELISA). Lead (Pb), cadmium (Cd) and manganese (Mn) levels in whole blood were measured using graphite furnace atomic absorption spectrometry (GFAAS). The prevalence of children with ADHD symptoms in Guiyu was 18.6%, with the percentage of children suspected to have behavior problems being 46.2% or 46.5%, based on the Rutter parents' or teachers' scale scores, respectively. Child blood levels of Pb, Cd, and Mn correlated with certain behavioral abnormalities, such as conduct problems and antisocial behavior. Serum S100 beta levels were associated with heavy metal levels in blood, and certain behavioral abnormalities. These findings suggest that exposure to various environmental heavy metals in Guiyu might result in child behavior disorders. Results also indicate that S100 beta may provide information for laboratory evaluation of neurotoxicity. (C) 2014 Elsevier Inc. All rights reserved.

Resistance and tolerance are two complementary mechanisms to reduce the detrimental effects of parasites, pathogens, and production diseases on host performance. Using body weight and ascites data on domesticated chicken Gallus gallus domesticus, we demonstrate the use of random regression animal model and covariance functions to estimate genetic parameters for ascites resistance and tolerance and illustrate the way individual variation in resistance and tolerance induce both genotype re-ranking and changes in variation of host performance along increasing ascites severity. Tolerance to ascites displayed significant genetic variance, with the estimated breeding values of tolerance slope ranging from strongly negative (very sensitive genotype) to weakly negative (less sensitive). Resistance to ascites had heritability of 0.34. Both traits are hence expected to respond to selection. The two complementary defense strategies, tolerance and resistance, were genetically independent. Ascites induced changes to the correlations between ascites resistance and body weight, with the genetic correlations being weak when birds were ascites-free but moderately negative when both healthy and affected birds were present. This likely results because ascites reduces growth, and thus high ascites incidence is genetically related to low adult body weight. Although ascites induced elevated phenotypic and genetic variances in body weight of affected birds, heritability displayed negligible changes across healthy and affected birds. Ascites induced moderate genotype re-ranking in body weight, with the genetic correlation of healthy birds with mildly affected birds being unity but with severely affected birds 0.45. This study demonstrates a novel approach for exploring genetics of defense traits and their impact on genotype-by-environment interactions.

Background Gene variants on chromosome 17q12-21 are associated with an increased risk of childhood-onset asthma, a risk known to be modified by environmental tobacco smoke (ETS). Objectives To assess whether the association of rs2305480 on chromosome 17q12 in the GSDML gene with asthma-like symptoms in the first 4 years of life is modified by smoke exposure during fetal and early postnatal life. Methods We used data from two independent prospective cohort studies from fetal life onwards in the Netherlands. We genotyped rs2305480 and assessed maternal smoking during pregnancy and ETS exposure at the age of 2. Asthma-like symptoms, defined as any reported wheezing, shortness of breath or dry nocturnal cough, were reported by parents when the children were 1, 2, 3, and 4 years. Analyses were based on a total group of 4461 Caucasian children. Results The G risk-allele of rs2305480 was associated with asthma-like symptoms [overall odds ratio 1.17 (1.11, 1.24), 2.66E-9]. The effect of rs2305480 on asthma-like symptoms was stronger among children who were exposed to smoke during fetal life (P-interaction = 0.04). Smoke exposure in early postnatal life was also associated with an increased effect of the 17q12 single nucleotide polymorphism (SNP) on asthma-like symptoms (P-interaction = 5.06E-4). These associations were consistent in both cohorts. Conclusion A 17q12 variant, rs2305480, was associated with asthma-like symptoms in preschool children, and this association was modified by smoke exposure already during fetal life, and in infancy. Further investigation regarding SNPs in linkage disequilibrium with rs2305480 in relation to pathophysiological pathways is needed.

Distributing animals from a single breeding program to a global market may not satisfy all producers, as they may differ in market objectives and farming environments. Analytic hierarchy process (AHP) is used to estimate preferences, which can be aggregated to consensus preference values using weighted goal programming (WGP). The aim of this study was to use an AHP-WGP based approach to derive desired genetic gains for rainbow trout breeding, and to study whether breeding trait preferences vary depending on commercial products and farming environments. Two questionnaires were sent out, Q-A and Q-B. Q-A was distributed to 178 farmers from 5 continents and used to collect information on commercial products and farming environments. In this questionnaire, farmers were asked to rank the 6 most important traits for genetic improvement from a list of 13 traits. Questionnaire B (Q-B) was sent to all farmers who responded to Q-A (53 in total). For Q-B, preferences of the 6 traits were obtained using pairwise comparison. Preference intensity was given in order to quantify (in % of a trait mean; G%) the degree to which one trait is preferred over the other. Individual preferences (Ind-P), social preferences (Soc-P), and consensus preferences (Con-P) were estimated using AHP and WGP. Desired gains were constructed by multiplying Con-P with G%. The analysis revealed that the 6 most important traits were thermal growth coefficient (TGC), survival (Surv), feed conversion ratio (FCR), condition factor (CF), fillet percentage (F%), and late maturation (LMat). Ranking of traits based on average Con-P values were Surv (0.271), FCR (0.246), TGC (0.246), LMat (0.090), F% (0.081), and CF (0.067). Corresponding desired genetic gains (in % of trait mean) were 1.63%, 1.87%, 1.67%, 1.29%, 0.06%, and 0.33%, respectively. The results from Con-P values show that trait preferences may vary for different types of commercial production or farming environments. This study demonstrated that combination of AHP and WGP can be used to derive desired gains for a breeding program, and to quantify differences due to variations market demand or production environment

Motivation: The sequencing of the human genome has made it possible to identify an informative set of >1 million single nucleotide polymorphisms (SNPs) across the genome that can be used to carry out genome-wide association studies (GWASs). The availability of massive amounts of GWAS data has necessitated the development of new biostatistical methods for quality control, imputation and analysis issues including multiple testing. This work has been successful and has enabled the discovery of new associations that have been replicated in multiple studies. However, it is now recognized that most SNPs discovered via GWAS have small effects on disease susceptibility and thus may not be suitable for improving health care through genetic testing. One likely explanation for the mixed results of GWAS is that the current biostatistical analysis paradigm is by design agnostic or unbiased in that it ignores all prior knowledge about disease pathobiology. Further, the linear modeling framework that is employed in GWAS often considers only one SNP at a time thus ignoring their genomic and environmental context. There is now a shift away from the biostatistical approach toward a more holistic approach that recognizes the complexity of the genotype–phenotype relationship that is characterized by significant heterogeneity and gene–gene and gene–environment interaction. We argue here that bioinformatics has an important role to play in addressing the complexity of the underlying genetic basis of common human diseases. The goal of this review is to identify and discuss those GWAS challenges that will require computational methods. Contact: jason.h.moore@dartmouth.edu

Motivation: The sequencing of the human genome has made it possible to identify an informative set of > 1 million single nucleotide polymorphisms (SNPs) across the genome that can be used to carry out genome-wide association studies (GWASs). The availability of massive amounts of GWAS data has necessitated the development of new biostatistical methods for quality control, imputation and analysis issues including multiple testing. This work has been successful and has enabled the discovery of new associations that have been replicated in multiple studies. However, it is now recognized that most SNPs discovered via GWAS have small effects on disease susceptibility and thus may not be suitable for improving health care through genetic testing. One likely explanation for the mixed results of GWAS is that the current biostatistical analysis paradigm is by design agnostic or unbiased in that it ignores all prior knowledge about disease pathobiology. Further, the linear modeling framework that is employed in GWAS often considers only one SNP at a time thus ignoring their genomic and environmental context. There is now a shift away from the biostatistical approach toward a more holistic approach that recognizes the complexity of the genotype-phenotype relationship that is characterized by significant heterogeneity and gene-gene and gene-environment interaction. We argue here that bioinformatics has an important role to play in addressing the complexity of the underlying genetic basis of common human diseases. The goal of this review is to identify and discuss those GWAS challenges that will require computational methods.

SummarySurvival from birth to a reproductive adult is a challenge that only robust individuals resistant to a variety of mortality factors will overcome. To assess whether survival traits share genetic architecture throughout the life cycle, we estimated genetic correlations for survival within fingerling stage, and across egg, fingerling and grow-out stages in farmed rainbow trout. Genetic parameters of survival at three life cycle stages were estimated for 249 166 individuals originating from ten year classes of a pedigreed population. Despite being an important fitness component, survival traits harboured significant but modest amount of genetic variation (h2=0·07–0·27). Weak associations between survival during egg-fry and fingerling periods, between early and late fingerling periods (rG=0·30) and generally low genetic correlations between fingerling and grow-out survival (meanrG=0·06) suggested that life-stage specific survival traits are best regarded as separate traits. However, in the sub-set of data with detailed time of death records, positive genetic correlations between early and late fingerling survival (rG=0·89) showed that during certain years the best genotypes in the early period were also among the best in the late period. That survival across fingerling period can be genetically the same, trait was indicated also by only slightly higher heritability (h2=0·15) estimated with the survival analysis of time to death during fingerling period compared to the analysis treating fingerling survival as a binary character (h2=0·11). The results imply that (1) inherited resistance against unknown mortality factors exists, but (2) ranking of genotypes changes across life stages.

This longitudinal study examines to what extent different depressive and anxiety disorders and clinical characteristics are associated with subsequent weight change, while controlling for baseline weight, sociodemographics, health status, psychotropic medication use and (un)healthy lifestyle factors. Data are from a sample of 2447 respondents aged 18-65 years of the Netherlands Study of Depression and Anxiety (NESDA). Baseline depressive disorders and anxiety disorders were determined with the Composite International Diagnostic Interview (CIDI). Weight at baseline and after 2 years was measured and analyzed as continuous change score (mean change in weight 1. kg) and in categories of significant weight loss (1. S.D., >6. kg). After full adjustment for covariates baseline comorbid anxiety and depressive disorder and baseline Major Depressive Disorder (MDD) were associated with significant 2-year weight gain. Both current and remitted MDD at baseline and a baseline dysthymia, but none of the anxiety disorders, were associated with significant weight loss. This longitudinal study confirms a U-curved link between depression and weight change over 2 years. Furthermore, a dose-response effect of depression severity on 2-year weight gain was found.

Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

The behavioral response of piglets in a backtest early in life seems indicative of their coping strategy at a later age. Coping characteristics may depend on the interaction between backtest classification and housing conditions. We studied whether growth rate and partitioning of energy in adult gilts were related to response in the backtest early in life, and to housing in groups or individual stalls. During the suckling period, female piglets were subjected to the backtest. Each piglet was restrained on its back for 1 min, and the number of escape attempts was scored. Thirty-six high-resisting gilts and 36 low-resisting gilts were selected. After weaning, pigs were housed in 12 groups of six (three high-resisting and three low-resisting). From 7 mo of age onward, 36 gilts out of six groups were housed in individual stalls, whereas the other gilts remained group housed. At 13 mo of age, gilts were housed in clusters of three (three high-resisting or three low-resisting) for an experimental period of 7 d in climatic respiration chambers. Group-housed gilts were loose housed, and stall-housed gilts were housed in stalls within the chamber. Despite the fact that high-resisting and low-resisting gilts did not differ (P = 0. 269) in initial BW, low-resisting gilts showed a higher (P = 0.039) ADG during the experimental period in association with a higher (P = 0.043) energy metabolizability. This suggests that, in line with the theory on coping strategies, high-resisting gilts may have more difficulties in adapting to a change in environment, (i.e., the change from home pen to climatic chamber). Group-and stall-housed gilts differed (P = 0.001) in initial BW, with group-housed gilts being heavier. During the experimental period, stall-housed gilts showed lower energy metabolizability (P = 0.001), lower energy retention (P = 0.001), and a higher energy requirement for maintenance (P = 0. 001) due to a higher activity-related heat production (P = 0.001). This finding suggests that stall housing might have a negative influence on performance and partitioning of energy when animals are adapting to a change in their environment.

International audience; High water use efficiency (WUE) can be achieved by coordination of biomass accumulation and water consumption. WUE is physiologically and genetically linked to carbon isotope discrimination (CID) in leaves of plants. A population of 148 recombinant inbred lines (RILs) of sunflower derived from a cross between XRQ and PSC8 lines was studied to identify quantitative trait loci (QTL) controlling WUE and CID, and to compare QTL associated with these traits in different drought scenarios. We conducted greenhouse experiments in 2011 and 2012 by using 100 balances which provided a daily measurement of water transpired, and we determined WUE, CID, biomass and cumulative water transpired by plants. Wide phenotypic variability, significant genotypic effects, and significant negative correlations between WUE and CID were observed in both experiments. A total of nine QTL controlling WUE and eight controlling CID were identified across the two experiments. A QTL for phenotypic response controlling WUE and CID was also significantly identified. The QTL for WUE were specific to the drought scenarios, whereas the QTL for CID were independent of the drought scenarios and could be found in all the experiments. Our results showed that the stable genomic regions controlling CID were located on the linkage groups 06 and 13 (LG06 and LG13). Three QTL for CID were co-localized with the QTL for WUE, biomass and cumulative water transpired. We found that CID and WUE are highly correlated and have common genetic control. Interestingly, the genetic control of these traits showed an interaction with the environment (between the two drought scenarios and control conditions). Our results open a way for breeding higher WUE by using CID and marker-assisted approaches and therefore help to maintain the stability of sunflower crop production.

Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p≤ 5 10) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 10) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations. © 2014 The American Society of Human Genetics.