Substantial Genetic Progress in the International Apis mellifera carnica Population Since the Implementation of Genetic Evaluation

The Apis mellifera carnica subspecies of the honeybee has long been praised for its gentleness and good honey yield before systematic breeding efforts began in the early 20th century. However, before the introduction of modern techniques of genetic evaluation (best linear unbiased prediction, BLUP) and a computerized data management in the mid 1990s, genetic progress was slow. Here, the results of the official breeding value estimation in BeeBreed.eu are analyzed to characterize breeding progress and inbreeding. From about the year 2000 onward, the genetic progression accelerated and resulted in a considerable gain in honey yield and desirable properties without increased inbreeding coefficients. The prognostic quality of breeding values is demonstrated by a retrospective analysis. The success of A. m. carnica breeding shows the potential of BLUP-based breeding values and serves as an example for a large-scale breeding program.Peer Reviewe

Association of vitamin D status with arterial blood pressure and hypertension risk : a mendelian randomisation study

Peer reviewe

GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies

Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency 1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease

Epidemiological studies with environmental relevance in Germany

Unsere Umwelt beeinflusst Gesundheit und Wohlbefinden des Menschen, von der Geburt bis ins hohe Alter. In diesem Überblick werden die wichtigsten epidemiologischen Studien und Gesundheitsmonitoringsysteme in Deutschland erläutert, die unter anderem auch Umwelteinflüsse in verschiedenen Bevölkerungsgruppen untersuchen und Gesundheitseffekte abschätzen. Die darin jeweils untersuchten Umweltfaktoren werden beschrieben. Diese Studien an Kindern und Erwachsenen schaffen eine Basis für Vorhersagen und präventive Maßnahmen. Die hohe Anzahl der erfassten umweltbezogenen Faktoren und die Intensität ihrer Untersuchung unterscheiden sich in den Studien, ebenso wie die (phänotypische) Charakterisierung der Studienteilnehmenden. Dennoch bilden die gewonnenen Daten eine Grundlage für die zukünftige Forschungsarbeit. Hierzu ist allerdings eine flächendeckende dauerhafte Erfassung der Daten zu den verschiedenen Umweltfaktoren notwendig. Da der Anteil der in städtischen Gebieten lebenden Bevölkerung in Zukunft weiter steigen wird, werden Umweltfaktoren wie Luftverschmutzung, Lufttemperatur, Lärm, aber auch soziale Ungerechtigkeit zukünftig die Gesundheit und Lebensqualität der Bevölkerung maßgeblich beeinflussen. Die Herausforderung einer alternden Gesellschaft, aber auch die mögliche Adaptation der Bevölkerung an diverse Umweltstimuli machen einen multidisziplinären Ansatz erforderlich. Gerade aus umweltepidemiologischer Sicht sind hier die gesammelten Daten der in diesem Artikel aufgezeigten Kohortenstudien in Deutschland ein wertvoller Schatz, denn nur damit können Zusammenhänge zwischen Umwelteinflüssen und Gesundheit erforscht und public-health-relevante präventive Maßnahmen identifiziert werden. Die NAKO-Gesundheitsstudie, die in den kommenden Jahrzehnten die größte verfügbare Ressource für Gesundheitsdaten sein wird, sollte in zukünftige Aktivitäten zur Erforschung von Umwelteinflüssen eingebunden werden.Our environment is a major factor in determining health and well-being throughout life, from conception into old age. This overview illustrates the most important epidemiological studies and health monitoring systems in Germany, which investigate environmental influences in various population subgroups and estimate related health effects. Environmental factors examined in each study are described. The mentioned studies in children and adults build the basis for predictions and preventive measures. The number of the assessed environmental factors, the depth of the examinations as well as the (phenotypical) characterization of the study participants differ. Still, the obtained data build a base for important future research. However, for this, a permanent and Germany-wide assessment of environmental factors is necessary. The proportion of the European population living in urban areas is projected to increase in the future. Therefore, environmental factors such as air pollution, air temperature, and noise, but also social inequality, are likely to have a negative effect on health and quality of life of the population. The challenge of the aging population as well as potential adaptation processes to the diverse environmental stimuli requires multidisciplinary approaches. From an environmental epidemiology view, the collected data from the described studies are of immense value because only with this data can associations between environment and health be investigated and public health-relevant preventive measures be identified. The NAKO health study will be the largest resource of health data and should therefore be included in future activities related to the investigation of environmental health effects in Germany.Peer Reviewe

GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Abstract Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies

Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p &lt;5 x 10(-8)). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.</p