The Krümmel (Germany) Childhood Leukaemia Cluster: a review and update.

The debate surrounding possible adverse health effects from the civil use of nuclear power under normal operating conditions has been on-going since its introduction. It was particularly intensified by the detection of three leukaemia clusters near nuclear installations, i.e. near the reprocessing plants in Sellafield and Dounreay, UK, and near the Krümmel nuclear power plant, Germany, the last of which commenced between 1990 and 1991 and was first described in 1992; it continued until 2003, and an elevated risk up to 2005 has been reported in the literature. A number of expert commissions and working groups were set up by the governments of the German federal states of Lower Saxony and Schleswig-Holstein to investigate the possible causes of the cluster. An overview of the many risk factors that were investigated as a possible explanation of the Krümmel cluster is given here, focussing on radiation, but also including other risk factors. Further, results from related epidemiological and cytogenetic studies are described. In summary, the cause of the occurrence of the Krümmel cluster has to be considered as unknown. Further research on the causes of childhood leukaemia is needed, focussing on epigenetics and on gene-environment interaction. An update of the leukaemia incidence around the Krümmel site shows that the incidence rates are now comparable to the average rate in Germany.

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.

A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila.

Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Therefore, we conducted high-density genome-wide association studies for sleep duration in seven European populations (N=4251). We identified an intronic variant (rs11046205; P=3.99 × 10(-8)) in the ABCC9 gene that explains ≈5% of the variation in sleep duration. An influence of season and chronotype on sleep duration was solely observed in the replication sample (N=5949). Meta-analysis of the associations found in a subgroup of the replication sample, chosen for season of entry and chronotype, together with the discovery results showed genome-wide significance. RNA interference knockdown experiments of the conserved ABCC9 homologue in Drosophila neurons renders flies sleepless during the first 3 h of the night. ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), serving as a sensor of intracellular energy metabolism.

Feasibility and quality development of biomaterials in the pretest studies of the German National Cohort.

BACKGROUND: The German National Cohort (GNC) is designed to address research questions concerning a wide range of possible causes of major chronic diseases (e.g. cancer, diabetes, infectious, allergic, neurologic and cardiovascular diseases) as well as to identify risk factors and prognostic biomarkers for early diagnosis and prevention of these diseases. The collection of biomaterials in combination with extensive information from questionnaires and medical examinations represents one of the central study components. OBJECTIVES: In two pretest studies of the German National Cohort conducted between 2011 and 2013, a range of biomaterials from a defined number of participants was collected. Ten study centres were involved in pretest 1 and 18 study centres were involved in pretest 2. Standard operation procedures (SOP) were developed and evaluated to minimize pre-analytical artefacts during biosample collection. Within the pretest studies different aspects concerning feasibility of sample collection/preparation [pretest 1 (a)] and quality control of biomarkers and proteome analyses were investigated [pretest 1 (b), (c)]. Additionally, recruitment of study participants for specific projects and examination procedures of all study centres in a defined time period according to common standards as well as transportation and decentralized storage of biological samples were tested (pretest 2). These analyses will serve as the basis for the biomaterial collection in the main study of the GNC starting in 2014. MATERIALS AND METHODS: Participants, randomly chosen from the population (n = 1000 subjects recruited at ten study sites in pretest 1) were asked to donate blood, urine, saliva and stool samples. Additionally, nasal and oropharyngeal swabs were collected at the study sites and nasal swabs were collected by the participants at home. SOPs for sample collection, preparation, storage and transportation were developed and adopted for pretest 2. In pretest 2, 18 study sites (n = 599 subjects) collected biomaterials mostly identical to pretest 1. Biomarker analyses to test the quality of the biomaterials were performed. RESULTS: In pretest 1 and 2, it was feasible to collect all biomaterials from nearly all invited participants without major problems. The mean response rate of the subjects was 95 %. As one important result we found for example that after blood draw the cellular fraction should be separated from the plasma and serum fractions during the first hour with no significant variation for up to 6 h at 4 ℃ for all analysed biomarkers. Moreover, quality control of samples using a proteomics approach showed no significant clustering of proteins according to different storage conditions. All developed SOPs were validated for use in the main study after some adaptation and modification. Additionally, electronic and paper documentation sheets were developed and tested to record time stamps, volumes, freezing times, and aliquot numbers of the collected biomaterials. DISCUSSION: The collection of the biomaterials was feasible without major problems at all participating study sites. However, the processing times were in some cases too long. To avoid pre-analytical artefacts in sample collection, appropriate standardisation among the study sites is necessary. To achieve this, blood and urine collection will have to be adapted to specific conditions of usage of liquid handling robots, which will be available at all participating study centres in the main study of the GNC. Strict compliance with the SOPs, thorough training of the staff and accurate documentation are mandatory to obtain high sample quality for later analyses. The so obtained biomaterials represent a valuable resource for research on infectious and other common complex diseases in the GNC.

Integrative genetic and metabolite profiling analysis suggests altered phosphatidylcholine metabolism in asthma.

BACKGROUND: Genome-wide association studies (GWAS) have identified many risk loci for asthma, but effect sizes are small, and in most cases, the biological mechanisms are unclear. Targeted metabolite quantification that provides information about a whole range of pathways of intermediary metabolism can help to identify biomarkers and investigate disease mechanisms. Combining genetic and metabolic information can aid in characterizing genetic association signals with high resolution. This work aimed to investigate the interrelation of current asthma, candidate asthma risk alleles and a panel of metabolites. METHODS: We investigated 151 metabolites, quantified by targeted mass spectrometry, in fasting serum of asthmatic and nonasthmatic individuals from the population-based KORA F4 study (N = 2925). In addition, we analysed effects of single-nucleotide polymorphisms (SNPs) at 24 asthma risk loci on these metabolites. RESULTS: Increased levels of various phosphatidylcholines and decreased levels of various lyso-phosphatidylcholines were associated with asthma. Likewise, asthma risk alleles from the PDED3 and MED24 genes at the asthma susceptibility locus 17q21 were associated with increased concentrations of various phosphatidylcholines with consistent effect directions. CONCLUSIONS: Our study demonstrated the potential of metabolomics to infer asthma-related biomarkers by the identification of potentially deregulated phospholipids that associate with asthma and asthma risk alleles.

Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe.

Recent molecular studies have implicated common alleles of small to moderate effect and rare alleles with larger effect sizes in the genetic architecture of schizophrenia (SCZ). It is expected that the reliable detection of risk variants with very small effect sizes can only be achieved through the recruitment of very large samples of patients and controls (that is tens of thousands), or large, potentially more homogeneous samples that have been recruited from confined geographical areas using identical diagnostic criteria. Applying the latter strategy, we performed a genome-wide association study (GWAS) of 1169 clinically well characterized and ethnically homogeneous SCZ patients from a confined area of Western Europe (464 from Germany, 705 from The Netherlands) and 3714 ethnically matched controls (1272 and 2442, respectively). In a subsequent follow-up study of our top GWAS results, we included an additional 2569 SCZ patients and 4088 controls (from Germany, The Netherlands and Denmark). Genetic variation in a region on chromosome 11 that contains the candidate genes AMBRA1, DGKZ, CHRM4 and MDK was significantly associated with SCZ in the combined sample (n=11 540; P=3.89 × 10(-9), odds ratio (OR)=1.25). This finding was replicated in 23 206 independent samples of European ancestry (P=0.0029, OR=1.11). In a subsequent imaging genetics study, healthy carriers of the risk allele exhibited altered activation in the cingulate cortex during a cognitive control task. The area of interest is a critical interface between emotion regulation and cognition that is structurally and functionally abnormal in SCZ and bipolar disorder.

Bipolar disorder risk alleles in children with ADHD.

Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) may share common genetic risk factors as indicated by the high co-morbidity of BD and ADHD, their phenotypic overlap especially in pediatric populations, the high heritability of both disorders, and the co-occurrence in families. We therefore examined whether known polygenic BD risk alleles are associated with ADHD. We chose the eight best SNPs of the recent genome-wide association study (GWAS) of BD patients of German ancestry and the nine SNPs from international GWAS meeting a 'genome-wide significance' level of α = 5 × 10(-8). A GWAS was performed in 495 ADHD children and 1,300 population-based controls using HumanHap550v3 and Human660 W-Quadv1 BeadArrays. We found no significant association of childhood ADHD with single BD risk alleles surviving adjustment for multiple testing. Yet, risk alleles for BD and ADHD were directionally consistent at eight of nine loci with the strongest support for three SNPs in or near NCAN, BRE, and LMAN2L. The polygene analysis for the BP risk alleles at all 14 loci indicated a higher probability of being a BD risk allele carrier in the ADHD cases as compared to the controls. At a moderate power to detect association with ADHD, if true effects were close to estimates from GWAS for BD, our results suggest that the possible contribution of BD risk variants to childhood ADHD risk is considerably lower than for BD. Yet, our findings should encourage researchers to search for common genetic risk factors in BD and childhood ADHD in future studies.

Association of a human G-protein beta3 subunit variant with hypertension.

Hypertension is a common disorder of multifactorial origin that constitutes a major risk factor for cardiovascular events such as stroke and myocardial infarction. Previous studies demonstrated an enhanced signal transduction via pertussis toxin-sensitive G proteins in lymphoblasts and fibroblasts from selected patients with essential hypertension. We have detected a novel polymorphism (C825T) in exon 10 of the gene encoding the beta3 subunit of heterotrimeric G proteins (GNB3). The T allele is associated with the occurrence of a splice variant, GNB3-s (encoding G beta3-s), in which the nucleotides 498-620 of exon 9 are deleted. This in-frame deletion causes the loss of 41 amino acids and one WD repeat domain of the G beta subunit. By western-blot analysis, G beta3-s appears to be predominantly expressed in cells from individuals carrying the T allele. Significant enhancement of stimulated GTPgammaS binding to Sf9 insect cells expressing G beta3-s together with G alpha(i)2 and G gamma5 indicates that this splice variant is biologically active. Genotype analysis of 427 normotensive and 426 hypertensive subjects suggests a significant association of the T allele with essential hypertension.

FADS gene cluster modulates the effect of breastfeeding on asthma. Results from the GINIplus and LISAplus studies.

BACKGROUND: The protective effect of breastfeeding (BF) on the development of asthma has been widely recognized, even if not all results have been consistent. Gene variants of the FADS gene cluster have a major impact on fatty acid composition in blood and in breast milk. Therefore, we evaluated the influence of the FADS1 FADS2 gene cluster polymorphisms on the association between BF and asthma. METHODS: The analysis was based on data (N=2245) from two German prospective birth cohort studies. Information on asthma and BF during the first 6 months was collected using questionnaires completed by the parents. Logistic regression modelling was used to analyse the association between exclusive BF and ever having asthma stratified by genotype. RESULTS: In the stratified analyses, BF for 3 or 4 months after birth had a protective effect for heterozygous and homozygous carriers of the minor allele (adjusted odds ratio between 0.37 (95% CI: 0.18-0.80) and 0.42 (95% CI: 0.20-0.88). Interaction terms of BF with genotype were significant and ranged from -1.17 (P-value: 0.015) to -1.33 (0.0066). Moreover, heterozygous and homozygous carriers of the minor allele who were exclusively breastfed for 5 or 6 months after birth had a reduced risk of asthma [0.32 (0.18-0.57) to 0.47 (0.27-0.81)] in the stratified analyses. For individuals carrying the homozygous major allele, BF showed no significant effect on the development of asthma. CONCLUSIONS: The association between exclusive BF and asthma is modified by the genetic variants of FADS genotypes in children.

Growth velocity during infancy and onset of asthma in school-aged children.

BACKGROUND: Growth velocities during infancy might affect the risk of asthma in childhood. This study examines the association between peak height and weight velocities during the first 2 years of life and onset of asthma and wheeze up to 10 years of age. METHODS: Data from 9086 children who participated in the GINIplus and LISAplus birth cohorts were analyzed. Information on asthma was requested annually from 1 to 10 years and information on wheeze at 1, 2, 4, 6, and 10 years. Peak height and weight velocities were calculated using height and weight measurements obtained between birth and 2 years of age. Cox proportional hazards models and generalized linear mixed models were calculated after adjustment for potential confounding factors including birth weight and body mass index at 10 years of age. RESULTS: Per interquartile range increase in peak weight velocity (PWV), the risk of asthma increased significantly (adjHR: 1.22; CI: 1.02-1.47). The relationship between peak height velocity (PHV) and onset of asthma was nonsignificant (adjHR: 1.08; CI: 0.88-1.31). Wheeze was not significantly associated with PHV or with PWV (adjOR: 1.07; CI: 0.64-1.77 and adjOR: 1.11; CI: 0.68-1.79, respectively). CONCLUSIONS: Weight gain during infancy is positively associated with physician-diagnosed asthma in school-aged children.

Evidence of the contribution of the X chromosome to systemic sclerosis susceptibility: association with the functional IRAK1 196Phe/532Ser haplotype.

OBJECTIVE: Several autoimmune disorders, including systemic sclerosis (SSc), are characterized by a strong sex bias. To date, it is not known whether genes on the sex chromosomes influence SSc susceptibility. Recently, an IRAK1 haplotype that contains the 196Phe functional variant (rs1059702), located on Xq28, was found to confer susceptibility to systemic lupus erythematosus (SLE). This study was undertaken to test for an association between SSc and the IRAK1 SLE risk haplotype. METHODS: We tested for an association with the IRAK1 SLE risk haplotype in a discovery set of 849 SSc patients and 625 controls. IRAK1 rs1059702 was further genotyped in a replication set, which included Caucasian women from Italy (493 SSc patients and 509 controls) and Germany (466 SSc patients and 1,083 controls). RESULTS: An association between the IRAK1 haplotype and SSc was detected in the discovery set. In both the discovery and replication sets, the rs1059702 TT genotype was found to be associated with specific SSc subsets, highlighting a potential contribution to disease severity. A meta-analysis provided evidence of an association of both the T allele and TT genotype with the overall disease, with an odds ratio (OR) of 1.20 and 95% confidence interval (95% CI) of 1.06-1.35 for the T allele (P = 0.003) and an OR of 1.49 and 95% CI of 1.06-2.10 for the TT genotype (P = 0.023). However, the most notable associations were observed with the diffuse cutaneous, anti-topoisomerase I antibody positive, and SSc-related fibrosing alveolitis subsets (OR 2.35 [95% CI 1.51-3.66], P = 1.56 × 10(-4), OR 2.84 [95% CI 1.87-4.32], P = 1.07 × 10(-6), and OR 2.09 [95% CI 1.35-3.24], P = 9.05 × 10(-4), respectively). CONCLUSION: Our study provides the first evidence of an association between IRAK1 and SSc, demonstrating that a sex chromosome gene directly influences SSc susceptibility and its phenotypic heterogeneity.

Association of gas cooking with children's respiratory health: results from GINIplus and LISAplus birth cohort studies.

UNLABELLED: Previous studies have found inconsistent results on the association between asthma in children and gas cooking emissions. We aimed to assess the effects of the long-term exposure to gas cooking on the onset of asthma and respiratory symptoms, focusing on wheezing, in children from two German birth cohorts: LISAplus and GINIplus. A total of 5078 children were followed until the age of 10 years. Asthma, wheezing, gas cooking, and exposure to other indoor factors were assessed through parental reported questionnaires administered periodically. Logistic and multinomial regressions adjusting for potential confounders were performed. The prevalence of asthma and persistent wheezing was higher among children exposed to gas cooking but the results were not statistically significant. Exposure to gas cooking was positively associated (P-value < 0.05) with exposure to other indoor factors (dampness, environmental tobacco smoke, and pets). Our results did not show a statistically significant association between the exposure to gas cooking and children's respiratory health. PRACTICAL IMPLICATIONS: These analyses are consistent with the assumption of no effect of the exposure to low doses of nitrogen dioxide. The strong positive associations found between gas cooking and other indoor factors highlight the importance of considering other indoor factors when assessing health effects of gas cooking. Low-dose exposure to indoor nitrogen dioxide through gas cooking might not contribute to increase the risk of asthma and respiratory symptoms in children.

Genome-wide association study identifies a new locus for coronary artery disease on chromosome 10p11.23.

AIMS: Recent genome-wide association (GWA) studies identified 10 chromosomal loci for coronary artery disease (CAD) or myocardial infarction (MI). However, these loci explain only a small proportion of the genetic variability of these pertinent diseases. We sought to identify additional CAD/MI loci by applying a three-stage approach. METHODS AND RESULTS: We genotyped n = 1157 MI cases and n = 1748 controls from a population-based study population [German MI Family Study (GerMIFS) III (KORA)] with genome-wide SNP arrays. At this first stage, n = 462 SNPs showed association with MI at P<1 × 10(-3) in two-sided logistic regression. In a second stage, 415 of these SNPs were evaluated in silico in two independent GWA samples, the GerMIFS I (875 cases/1644 controls) and GerMIFS II (1222 cases/1298 controls). Nine SNPs, representing three regions, displayed consistent replication in this in silico analysis (P<0.05 for each GWA sample): five SNPs at 9p21.3, a well-known CAD/MI locus, two SNPs at 10p11.21, and two SNPs at 2p24.3. Wet-lab replication, i.e. the third stage, of SNP rs3739998 (representing the novel locus at 10p11.21, p.S1002T in the KIAA1462 gene) in additional 5790 cases and 5302 controls confirmed the association (P=9.54 × 10(-4)), but not for the 2p24.3 locus. The combined P-value across all stages for SNP rs3739998 is P=1.27 × 10(-11) [odds ratio (OR) = 1.15 (1.11-1.20)]. CONCLUSION: Analysis of a GWA study followed by in silico and wet-lab replication steps identified the KIAA1462 gene, encoding a yet uncharacterized protein, on chromosome 10p11.23 with genome-wide significant association for CAD/MI. Further studies are needed to characterize the functional role of this locus in the aetiology of these diseases.

[The German National Cohort]. / Die Nationale Kohorte.

The German National Cohort (GNC) is a joint interdisciplinary endeavour of scientists from the Helmholtz Association, universities and other German research institutes. Its aim is to investigate the development of major chronic diseases (cardiovascular diseases, cancer, diabetes, neurodegenerative psychiatric diseases, pulmonary and infectious diseases), the subclinical stages and functional changes. In 18 study centres across Germany, a representative sample of the general population will be drawn to recruit in total 200,000 men and women aged 20-69 years. In addition to interviews and questionnaires, the baseline assessment includes a series of medical examinations and the collection of a diverse range of biomaterials. In 20% of the participants, an intensified assessment programme is foreseen. Also in 40,000 participants, magnetic resonance imaging of the whole body, heart and brain will be performed. After 5 years, a follow-up examination will be performed in all subjects and active follow-up by postal questionnaires is planned every 2-3 years. The GNC will provide an excellent basis for future population-based epidemiology in Germany and results will help identify new and tailored strategies for prevention, prediction and early detection of major diseases.

Respiratory health in children, and indoor exposure to (1,3)-ß-D-glucan, EPS mould components and endotoxin.

For a long time, exposure to mould and dampness-derived microbial components was considered a risk factor for the development of respiratory diseases and symptoms. Some recent studies suggested that early childhood exposure to mould components, such as (1,3)-ß-D-glucan and extracellular polysaccharides (EPSs), may protect children from developing allergy. We investigated the association of exposure to (1,3)-ß-D-glucan, EPS and endotoxin with asthma and allergies in 6-yr-old children. This investigation was the follow-up to a nested case-control study among three European birth cohorts. Children from two ongoing birth cohort studies performed in Germany (n = 358) and one in the Netherlands (n = 338) were selected. Levels of (1,3)-ß-D-glucan, EPS and endotoxin were measured in settled house dust sampled from children's mattresses and living-room floors when the children were, on average, 5 yrs of age. At the age of 6 yrs, health outcome information was available for 678 children. In the two German subsets, domestic EPS and endotoxin exposure from children's mattresses were significantly negatively associated with physician-diagnosed asthma (OR per interquartile range increase 0.60 (95% CI 0.39-0.92) and 0.55 (95% CI 0.31-0.97), respectively). In addition, EPS exposure was inversely related to physician-diagnosed allergic rhinitis (OR 0.50, 95% CI 0.31-0.81). For the Dutch population, no associations were observed between exposure to microbial agents and respiratory health outcomes. We found inverse associations between domestic exposure to EPS and endotoxin from children's mattresses, and doctor-diagnosed asthma and rhinitis in German, but not in Dutch, school children. The reasons for the differences between countries are not clear.

FADS gene variants modulate the effect of dietary fatty acid intake on allergic diseases in children.

BACKGROUND: The association between dietary fatty acid intake and the development of atopic diseases has been inconsistent. This could be due to inter-individual genetic differences in fatty acid metabolism. OBJECTIVE: The aim of the current study was to assess the influence of FADS1 FADS2 gene cluster polymorphisms on the association between dietary fatty acid intake and atopic diseases and allergic sensitization in 10-year-old children. METHODS: The analysis was based on data from two German prospective birth cohort studies. Data on margarine and fatty acid intake were collected using a food frequency questionnaire. Information on atopic diseases was collected using a questionnaire completed by the parents. Specific IgE against common food and inhalant allergens were measured. Six variants of the FADS1 FADS2 gene cluster (rs174545, rs174546, rs174556, rs174561, rs174575 and rs3834458) were tested. Logistic regression modelling, adjusted for gender, age, maternal education level and study centre, was used to analyse the association between fatty acid intake and atopic diseases stratified by genotype. RESULTS: No significant association was found between the six FADS single nucleotide polymorphisms (SNPs) and allergic diseases or atopic sensitization. The total n-3/total n-6 ratio was positive associated with an increased risk of hayfever in homozygous major allele carriers ranging from an adjusted odds ratios of 1.25 (95%-CI: 1.00-1.57) to 1.31 (95%-CI: 1.01-1.69) across the six tested SNPs although this association was not significant anymore after correcting for multiple testing. Daily margarine intake was significantly associated with asthma [1.17 (1.03-1.34) to 1.22 (1.06-1.40)] in individuals carrying the homozygous major allele. This association was also significant after correcting for multiple testing. CONCLUSIONS & CLINICAL RELEVANCE: The association between dietary intake of fatty acids and allergic diseases might be modulated by FADS gene variants in children.

Association between attendance of day care centres and increased prevalence of eczema in the German birth cohort study LISAplus.

BACKGROUND: Day care centre attendance is much more common in East than in West Germany. Although there is evidence that early day care might be protective against atopic diseases, several studies have shown a higher prevalence of childhood eczema in East Germany compared to West Germany. OBJECTIVES: To compare prevalence and cumulative incidence of eczema in a birth cohort study in East and West Germany and to identify risk factors that are associated with eczema, which might explain regional differences. METHODS: We used data from the ongoing population-based birth cohort study Influence of Life-style factors on the development of the Immune System and Allergies in East and West Germany Plus the influence of traffic emissions and genetics. In 1997, 3097 children from study areas in East and West Germany were recruited. Cumulative incidence and 1-year prevalences of eczema up to the age of 6 years were determined from yearly questionnaires. Cox regression and generalized estimating equations/logistic regression were used to quantify regional differences and to identify risk factors that might explain them. RESULTS: Prevalence and incidence of eczema were higher in children living in East Germany than those living in West Germany. We identified 11 risk factors that showed significant regional differences. From these factors, only 'day care attendance during the first 2 years of life' was significantly associated with eczema (odds ratio 1.56, 95% confidence interval CI 1.31-1.86). The regional differences in eczema could be explained by differences in early day care utilization. CONCLUSION: Day care centre attendance is associated with an increased prevalence and incidence of eczema. Regional differences in eczema prevalence could be explained by regional differences in utilization of early day care.

Infant eczema, infant sleeping problems, and mental health at 10 years of age: the prospective birth cohort study LISAplus.

BACKGROUND: Cross-sectional studies suggest an association between eczema and mental health problems, possibly modified by sleeping problems, but prospective evidence is missing. We aimed to prospectively investigate the relationship between infant eczema (within first 2 years of age), infant sleeping problems (within first 2 years of age), and the risk of mental health problems at 10 years of age. METHODS: Between 1997 and 1999, a population-based birth cohort was recruited in Munich, Leipzig, Wesel, and Bad Honnef, Germany, and followed until 10 years of age. Physician-diagnosed eczema, parent-reported sleeping problems, and known environmental risk factors for atopy were regularly assessed until 10 years of age. Mental health was measured using the Strengths and Difficulties Questionnaire (parent version) at 10 years of age. We applied logistic regression modeling adjusting for environmental and lifestyle factors, allergic comorbidity, and family history of eczema. RESULTS: From the original cohort of 3097 neonates, 1658 (54%) were followed until age 10, while 1578 (51%) were eligible for analysis. In the fully adjusted model, children with infant eczema were at increased risk of hyperactivity/inattention at 10 years of age [odds ratio (OR) 1.78; 95% confidence interval (95% CI) 1.02-3.09]. Infant eczema with concurrent sleeping problems predicted emotional problems [OR 2.63; 95% confidence interval (95% CI) 1.20-5.76] and conduct problems (OR 3.03; 95% CI 1.01-9.12) at 10 years of age. CONCLUSIONS: Infant eczema with concurrent sleeping problems appears to be a risk factor for the development of mental health problems.

Gene-PUFA interactions and obesity risk.

Although there are indications for modulatory effects of PUFA on associations between SNP and obesity risk, scientific evidence in human subjects is still scarce. The present analyses investigated interaction effects between SNP in candidate genes for obesity and PUFA in erythrocyte membranes on obesity risk. Within the second Bavarian Food Consumption Survey (cross-sectional, population-based), 568 adults provided blood samples. Fatty acid composition of erythrocyte membranes was analysed by means of GC. Genotyping was performed for twenty-one genes, including cytokines, adipokines, neurotransmitters and transcription factors. In addition, plasma IL-6 concentrations were analysed. For the statistical analysis, a logistic regression model assuming additive genetic effects was chosen. About 20 % of the study participants were classified as obese (BMI ≥ 30 kg/m(2)). Several significant gene-PUFA interactions were found, indicating regulatory effects of PUFA by gene variants of IL-2, IL-6, IL-18, TNF receptor family member 1B and 21, leptin receptor and adiponectin on obesity risk. After stratification by genotype, the strongest effects were found for rs2069779 (IL-2) and all tested PUFA as well as for rs1800795 (IL-6) and linoleic or arachidonic acid. The obesity risk of minor allele carriers significantly decreased with increasing fatty acid content. The genetic PUFA-IL-6 interaction was also reflected in plasma IL-6 concentrations. If replicated in a prospective study with sufficient statistical power, the results would indicate a beneficial effect of high PUFA supply for a substantial proportion of the population with respect to obesity risk.