A Genome-Wide Association Study of Attention Function in a Population-Based Sample of Children

BACKGROUND: Attention function filters and selects behaviorally relevant information. This capacity is impaired in some psychiatric disorders and has been proposed as an endophenotype for Attention-Deficit/Hyperactivity Disorder; however, its genetic basis remains largely unknown. This study aimed to identify single nucleotide polymorphism (SNPs) associated with attention function. MATERIALS AND METHODS: The discovery sample included 1655 children (7-12 years) and the replication sample included 546 children (5-8 years). Five attention outcomes were assessed using the computerized Attentional Network Test (ANT): alerting, orienting, executive attention, Hit Reaction time (HRT) and the standard error of HRT (HRTSE). A Genome-wide Association Study was conducted for each outcome. Gene set enrichment analyses were performed to detect biological pathways associated with attention outcomes. Additional neuroimaging analyses were conducted to test neural effects of detected SNPs of interest. RESULTS: Thirteen loci showed suggestive evidence of association with attention function (P<10-5) in the discovery sample. One of them, the rs4321351 located in the PID1 gene, was nominally significant in the replication sample although it did not survive multiple testing correction. Neuroimaging analysis revealed a significant association between this SNP and brain structure and function involving the frontal-basal ganglia circuits. The mTOR signaling and Alzheimer disease-amyloid secretase pathways were significantly enriched for alerting, orienting and HRT respectively (FDR<5%). CONCLUSION: These results suggest for the first time the involvement of the PID1 gene, mTOR signaling and Alzheimer disease-amyloid secretase pathways, in attention function during childhood. These genes and pathways have been proposed to play a role in neuronal plasticity, memory and neurodegenerative disease

Prenatal Omega-6:Omega-3 Ratio and Attention Deficit and Hyperactivity Disorder Symptoms

Objective: To evaluate whether higher omega-6:omega-3 (n-6:n-3) long-chain polyunsaturated fatty acid ratio in cord plasma is associated with more symptoms of attention deficit and hyperactivity disorder (ADHD) at 4 and 7 years of age. Study design: This study was based on a population-based birth cohort in Spain. N-6 arachidonic acid and n-3 eicosapentaenoic and docosahexaenoic acid concentrations were measured in cord plasma. At 4 years old, ADHD symptoms were reported by teachers through the ADHD Diagnostic and Statistical Manual of Mental Disorders, 4th ed checklist (n = 580). At 7 years old, ADHD symptoms were reported by parents through the Conners' Rating Scale-Revised (short form; n = 642). The ADHD variable was treated as continuous (score) and as dichotomous (symptom diagnostic criteria). Child and family general characteristics were prospectively collected through questionnaires. We applied pooled zero-inflated negative binomial and logistic regressions adjusted for covariates. Results: A higher omega-6:omega-3 long-chain polyunsaturated fatty acid ratio in cord plasma was associated with a higher ADHD index (incidence rate ratio, 1.13; 95% CI, 1.03, 1.23) at 7 years old. The association was not observed at 4 years old (incidence rate ratio, 1.04; 95% CI, 0.92-1.18). No associations were found using ADHD symptom diagnostic criteria. Conclusions: High prenatal omega-6:omega-3 long-chain polyunsaturated fatty acid ratio preceded the appearance of subclinical ADHD symptoms during mid-childhood. Our findings suggest that maternal diet during pregnancy may modulate the risk to develop long-term ADHD symptoms in the offspring

Genomics reveals the role of admixture in the evolution of structure among sperm whale populations within the Mediterranean Sea

In oceanic ecosystems, the nature of barriers to gene flow and the processes by which populations may become isolated are different from the terrestrial environment, and less well understood. In this study we investigate a highly mobile species (the sperm whale, Physeter macrocephalus) that is genetically differentiated between an open North Atlantic population and the populations in the Mediterranean Sea. We apply high-resolution single nucleotide polymorphism (SNP) analysis to study the nature of barriers to gene flow in this system, assessing the putative boundary into the Mediterranean (Strait of Gibraltar and Alboran Sea region), and including novel analyses on structuring among sperm whale populations within the Mediterranean basin. Our data support a recent founding of the Mediterranean population, around the time of the last glacial maximum, and show concerted historical demographic profiles in both the Atlantic and the Mediterranean. In each region there is evidence for a population decline around the time of the founder event. The largest decline was seen within the Mediterranean Sea where effective population size is substantially lower (especially in the eastern basin). While differentiation is strongest at the Atlantic/Mediterranean boundary, there is also weaker but significant differentiation between the eastern and western basins of the Mediterranean Sea. We propose, however, that the mechanisms are different. While post-founding gene flow was reduced between the Mediterranean and Atlantic populations, within the Mediterranean an important factor differentiating the basins is probably a greater degree of admixture between the western basin and the North Atlantic and some level of isolation between the western and eastern Mediterranean basins. Subdivision within the Mediterranean Sea exacerbates conservation concerns and will require consideration of what distinct impacts may affect populations in the two basins

Heritability and Genome-Wide Association Analyses of Sleep Duration in Children:The EAGLE Consortium

STUDY OBJECTIVES: Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration in children attributed to common single nucleotide polymorphisms (SNPs), (2) identify novel SNPs associated with sleep duration in children, and (3) investigate the genetic overlap of sleep duration in children and related metabolic and psychiatric traits.METHODS: We performed a population-based molecular genetic study, using data form the EArly Genetics and Life course Epidemiology (EAGLE) Consortium. 10,554 children of European ancestry were included in the discovery, and 1,250 children in the replication phase.RESULTS: We found evidence of significant but modest SNP heritability of sleep duration in children (SNP h(2) 0.14, 95% CI [0.05, 0.23]) using the LD score regression method. A novel region at chromosome 11q13.4 (top SNP: rs74506765, P = 2.27e-08) was associated with sleep duration in children, but this was not replicated in independent studies. Nominally significant genetic overlap was only found (rG = 0.23, P = 0.05) between sleep duration in children and type 2 diabetes in adults, supporting the hypothesis of a common pathogenic mechanism.CONCLUSIONS: The significant SNP heritability of sleep duration in children and the suggestive genetic overlap with type 2 diabetes support the search for genetic mechanisms linking sleep duration in children to multiple outcomes in health and disease.</p

Chapitre 34. Adaptations de l’agriculture à l’aridité dans les îles Canaries

Dans les régions extrêmement arides (Pluie = 150 mm, ETP = 1 800 mm) des îles Canaries, à l’est de Fuerteventura et de Lanzarote et au sud de Tenerife, l’agriculture a été maintenue depuis des décades par divers systèmes traditionnels de gestion du ruissellement. Ces systèmes ont montré leur efficacité durable pour augmenter la production agricole dans cet environnement peu favorable sans entraîner la dégradation des ressources en eau et en sols. Parmi d’autres, les techniques de capture du ruissellement (gavias) et de mulch de gravier (arenados) jouent encore localement un rôle important dans l’agriculture de certaines îles. Bien que le rôle majeur de ces systèmes est d’augmenter la disponibilité en eau pour les cultures hors irrigation, ces techniques permettent aussi la production agricole sur des sols naturellement salés et, pour certaines d’entre elles, sans apport d’engrais minéraux ou organiques. Dans ce chapitre sont décrits deux de ces techniques montrant leur intérêt pour résoudre certains problèmes de contraintes de l’agriculture en zones arides telles que le manque d’eau, la salinité et la sodicité, la faible fertilité des sols.In arid lands (Rain = 150 mm, PET = 1 800 mm) of Canary Islands (Fuerteventura, Lanzarote, Tenerife), agriculture has been sustained for decades by several traditional rainfed agricultural systems. These systems have been sustainable as a means to increase the crop production in very unfavourable environment without degradation of soil & water resources. Among these techniques, those based on runoff-capture (gavias) or on lithic-mulch (arenados) remain today a significant component of the agriculture on some islands. Although the primary goal is to increase the water supply for crops, making unnecessary conventional irrigation, equally important factors are that these techniques permit crop production in natural saline soils and sometimes without addition of mineral or organic fertilizers. In this chapter, the main techniques are described and data reported in order to show its efficiency solving environmental constraints such as lack of water, salinity and low fertility

Recycled Urban Wastewater for Irrigation of Jatropha curcas L. in Abandoned Agricultural Arid Land

In a global context in which obtaining new energy sources is of paramount importance, the production of biodiesel from plant crops is a potentially viable alternative to the use of fossil fuels. Among the species used to produce the raw material for biodiesel, Jatropha curcas L. (JCL) has enjoyed increased popularity in recent years, due partly to its ability to grow in degraded zones and under arid and semi-arid conditions. The present study evaluates the potential for JCL production under irrigation with non-conventional water resources in abandoned agricultural soils of the island of Fuerteventura (Canary Islands, Spain), which is one of the most arid parts of the European Union. JCL growth and productivity are compared during the first 39 months of cultivation in two soil types (clay-loam and sandy-loam) and with two irrigation water qualities: recycled urban wastewater (RWW) and desalinated brackish water (DBW). The results indicate that JCL growth (in terms of plant height and stem diameter) was significantly influenced both by soil type and water quality, with better development observed in the sandy-loam soil under RWW irrigation. Productivity, measured as cumulative seed production, was not affected by soil type but was affected by water quality. Production under RWW irrigation was approximately seven times greater than with DBW (mean ~2142 vs. 322 kg·ha−1). The higher nutrient content, especially P, K and Mg, and lower B content of the RWW were found to be key factors in the greater productivity observed under irrigation with this type of water

Using a multi-disciplinary approach to identify a critically endangered killer whale management unit.

International audienceA key goal for wildlife managers is identifying discrete, demographically independent conservation units.Previous genetic work assigned killer whales that occur seasonally in the Strait of Gibraltar (SoG) andkiller whales sampled off the Canary Islands (CI) to the same population. Here we present new analysesof photo-identification and individual genotypes to assess the level of contemporary gene flow andmigration between study areas, and analyses of biomarkers to assess ecological differences. We identified47 different individuals from 5 pods in the SoG and 16 individuals in the CI, with no matches foundbetween the areas. Mitochondrial DNA control region haplotype was shared by all individuals sampledwithin each pod, suggesting that pods have a matrifocal social structure typical of this species, whilstthe lack of shared mitogenome haplotypes between the CI and SoG individuals suggests that there waslittle or no female migration between groups. Kinship analysis detected no close kin between CI and SoGindividuals, and low to zero contemporary gene flow. Isotopic values and organochlorine pollutant loadsalso suggest ecological differences between study areas. We further found that one individual from a podwithin the SoG not seen in association with the other four pods and identified as belonging to a potentialmigrant lineage by genetic analyses, had intermediate isotopic values and contaminant between thetwo study areas. Overall our results suggest a complex pattern of social and genetic structuring correlatedwith ecological variation. Consequently at least CI and SoG should be considered as two differentmanagement units. Understanding this complexity appears to be an important consideration when monitoringand understanding the viability of these management units. Understand the viability will helpthe conservation of these threatened management units

Using a multi-disciplinary approach to identify a critically endangered killer whale management unit

A key goal for wildlife managers is identifying discrete, demographically independent conservation units. Previous genetic work assigned killer whales that occur seasonally in the Strait of Gibraltar (SoG) and killer whales sampled off the Canary Islands (CI) to the same population. Here we present new analyses of photo-identification and individual genotypes to assess the level of contemporary gene flow and migration between study areas, and analyses of biomarkers to assess ecological differences. We identified 47 different individuals from 5 pods in the SoG and 16 individuals in the CI, with no matches found between the areas. Mitochondrial DNA control region haplotype was shared by all individuals sampled within each pod, suggesting that pods have a matrifocal social structure typical of this species, whilst the lack of shared mitogenome haplotypes between the CI and SoG individuals suggests that there was little or no female migration between groups. Kinship analysis detected no close kin between CI and SoG individuals, and low to zero contemporary gene flow. Isotopic values and organochlorine pollutant loads also suggest ecological differences between study areas. We further found that one individual from a pod within the SoG not seen in association with the other four pods and identified as belonging to a potential migrant lineage by genetic analyses, had intermediate isotopic values and contaminant between the two study areas. Overall our results suggest a complex pattern of social and genetic structuring correlated with ecological variation. Consequently at least CI and SoG should be considered as two different management units. Understanding this complexity appears to be an important consideration when monitoring and understanding the viability of these management units. Understand the viability will help the conservation of these threatened management units.This work was funded by Loro Parque Foundation, CEPSA, Ministerio de Medio Ambiente, Fundación Biodiversidad, LIFE+ Indemares (LIFE07NAT/E/000732) and LIFE “Conservación de Cetáceos y tortugas de Murcia y Andalucía” (LIFE02NAT/E/8610), “Plan Nacional I+D+I ECOCET” (CGL2011-25543) of the Spanish “Ministerio de Economía y Competitividad”. R. d. S. and J. G. were supported by the Spanish Ministry of Economy and Competitiveness, through the Severo Ochoa Programme for Centres of Excellence in R+D+I (SEV-2012-0262)>, and also R. d. S. by the “Subprograma Juan de la Cierva”. Genetic analysis at the University of British Columbia was supported by the Vancouver Aquarium and assisted by Allyson Miscambell