[Show abstract][Hide abstract] ABSTRACT: Air pollution has been associated with increases in hospital admissions for cardiovascular diseases. This article aims to identify subgroups of individuals who exhibit early biological responses consistent with the health effects of ambient air pollution. Resting heart rates have been recorded in a cohort of 2681 men and women aged 25-64 yr who participated in the MONICA Augsburg survey during the winter 1984/1985 and in a reexamination during the winter 1987/1988. Increases in heart rate of 1.8 beats per minute (bpm) (95% confidence interval: 0.7 to 2.8 bpm) were observed during the air pollution episode compared to nonepisode days, adjusted for potential cardiovascular risk factors and meteorological parameters. Among persons whose plasma viscosity was above the 90th percentile, heart rates increased 5.1 bpm (95% confidence interval: 2.1 to 8.2 bpm) during the air pollution episode. Persons with normal values of plasma viscosity only had an increase of 1.4 bpm (95% confidence interval: 0.3 to 2.5 bpm) during the air pollution episode. Subjects with increased plasma viscosity showed a more pronounced acceleration in heart rate at rest, pointing toward a modification of the autonomic control of the heart during an air pollution episode.
[Show abstract][Hide abstract] ABSTRACT: Aiming to investigate fine-scale patterns of genetic heterogeneity in modern humans from a geographic perspective, a genetic geostatistical approach framed within a geographic information system is presented. A sample collected for prospective studies in a small area of southern Germany was analyzed. None indication of genetic heterogeneity was detected in previous analysis. Socio-demographic and genotypic data of German citizens were analyzed (212 SNPs; n = 728). Genetic heterogeneity was evaluated with observed heterozygosity (H O ). Best-fitting spatial autoregressive models were identified, using socio-demographic variables as covariates. Spatial analysis included surface interpolation and geostatistics of observed and predicted patterns. Prediction accuracy was quantified. Spatial autocorrelation was detected for both socio-demographic and genetic variables. Augsburg City and eastern suburban areas showed higher H O values. The selected model gave best predictions in suburban areas. Fine-scale patterns of genetic heterogeneity were observed. In accordance to literature, more urbanized areas showed higher levels of admixture. This approach showed efficacy for detecting and analyzing subtle patterns of genetic heterogeneity within small areas. It is scalable in number of loci, even up to whole-genome analysis. It may be suggested that this approach may be applicable to investigate the underlying genetic history that is, at least partially, embedded in geographic data.
International Journal of Genomics 08/2015; 2015(2):693193. DOI:10.1155/2015/693193 · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidemiological miner cohort data used to estimate lung cancer risks related to occupational radon exposure often lack cohort-wide information on exposure to tobacco smoke, a potential confounder and important effect modifier. We have developed a method to project data on smoking habits from a case-control study onto an entire cohort by means of a Monte Carlo resampling technique. As a proof of principle, this method is tested on a subcohort of 35,084 former uranium miners employed at the WISMUT company (Germany), with 461 lung cancer deaths in the follow-up period 1955–1998. After applying the proposed imputation technique, a biologically-based carcinogenesis model is employed to analyze the cohort's lung cancer mortality data. A sensitivity analysis based on a set of 200 independent projections with subsequent model analyses yields narrow distributions of the free model parameters, indicating that parameter values are relatively stable and independent of individual projections. This technique thus offers a possibility to account for unknown smoking habits, enabling us to unravel risks related to radon, to smoking, and to the combination of both.
[Show abstract][Hide abstract] ABSTRACT: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
[Show abstract][Hide abstract] ABSTRACT: Low Emission Zones (LEZs) were implemented as a measure for improving air quality of ambient air, especially in cities where the European limit values for PM10 (particulate matter with an aerodynamic diameter < 10 µm) were exceeded. Up to now 48 LEZs were introduced in Germany (by the end of 2014); however they differ significantly from city to city regarding size, implementation time and strictness of regulation. In general, the vehicles are identified by windscreen badges in a coloured code which is directly linked to the corresponding stages of European emission standards. In other European countries LEZs (or other measures such as Congestion Charge Zones) have been also implemented; however, there are no uniform regulations for LEZs in the different EU member states. The effects of LEZs on the air quality have already been investigated by dispersion modeling or increasingly also by analysis of PM10 measurement values. While initially inconsistent results were reported due to short time series of PM10 measurements, recent studies show a clear trend. In sufficiently large and strictly regulated LEZs a reduction of PM10 concentration between 5 and 10[%] (at traffic site partially above 10[%]) can be expected. The reduction of PM10 levels is in general more pronounced for the summer season compared to the winter season. In winter, additional particle sources (such as domestic heating, wood combustion, re-suspended dust due to the application of road salt for deicing) contribute significantly to the PM10 mass concentrations and consequently a measure regulating vehicle exhaust particles only becomes less effective. It has been shown that air pollutants which are emitted mainly by traffic and especially by diesel cars (elemental carbon (EC), diesel soot, ultrafine particles, PM2.5) are more affected by the implementation of LEZs. After the implementation of LEZ in Munich the average concentration of EC emitted by traffic decreased by 50[%]. In Berlin the diesel particle emissions were reduced by 63[%] compared to a business-as-usual scenario. The limit values for PM10 were introduced in 2005 mainly due to the adverse health effects of fine particles on respiratory and cardiovascular morbidity and mortality. The most health-relevant PM10 particle fraction consists mainly of traffic related particles and here especially of diesel soot particles. Therefore, the German regulations for LEZs promote using of diesel particulate filter (DPF) in diesel cars. Unfortunately, the evaluation of the LEZ effects is mostly restricted to PM10, a particle fraction containing on average only 20[%] of exhaust related particles. A 10[%] reduction of PM10 should lead to a reduction of the toxic and health-relevant diesel soot fraction by 50[%], which was already reported for some "efficient" LEZs. This means at the same time that the benefit of LEZs on human health is far greater than is presently visible from routine measurements of PM10. Overall, the results show that LEZs are proving successful as a measure for air pollution control when they are large enough and only few exemptions are granted. They decrease not only PM10 but, to a much higher degree, the health-relevant components (such as diesel soot) contained in PM10. Therefore, the benefit of the LEZs could be much better estimated by additional monitoring of diesel soot and elemental carbon in PM10.
Umweltmedizin in Forschung und Praxis 01/2015; 20(1):33-57.
[Show abstract][Hide abstract] ABSTRACT: Aim
Residential mobility during childhood has been associated with several adverse health outcomes. The present study investigates the influence of residential mobility during childhood measured by the frequency of moves, the child’s age at the time of the move and the total distance moved on the development of behavioural problems in school-age children.
Subject and methods
Data (N = 2,933) of two German population-based, prospective birth-cohort studies were used. Measurement of children’s residential mobility is based on the addresses at birth, 2, 6 and 10 years, which were collected by questionnaires and subsequently geocoded. Behavioural outcomes were assessed using the Strengths and Difficulties Questionnaire applied at 10-year follow-up. Multiple logistic regression analyses controlling for sex and age of the child, study centre, parental educational level, mother’s age at birth, single parent status and child’s time spent in front of a screen were applied.
Children with two or more relocations—odds ratio (OR) = 1.95, 95 % confidence interval (CI) = 1.23–3.11—who moved at school age (OR = 1.97, CI = 1.17–3.31) or who moved more than 50 km in total (OR = 1.76, CI = 1.03–3.00) showed a significantly increased risk for the development of behavioural problems measured by the Total Difficulties Score compared to children who have never moved. Moving during early childhood and moving only short distance (less than 10 km in total) were not associated with behavioural problems.
Increased residential mobility during childhood and especially moves at school age may negatively affect children’s later behaviour. Prevention may consist in parental or teacher’s support of children to cope with moving.
Journal of Public Health 10/2014; 21(1). DOI:10.1007/s10389-012-0522-y · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
[Show abstract][Hide abstract] ABSTRACT: Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25610 28), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11610 211) and 8q12 (minimum p value 1.82610 211) previously reported for MSE and myopia age at onset. We also used an intermarker linkage-disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. ''Replication-level'' association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.
PLoS ONE 09/2014; 9(9). DOI:10.1371/journal.pone.0107110 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
The genetic polymorphism concerning the ß3-subunit of platelet integrin receptor glycoprotein IIIa is held responsible for enhanced binding of adhesive proteins resulting in increased thrombogenic potential. Whether it is associated with mortality, HbA1c or platelet volume is tested prospectively in an epidemiological cohort.
Research design and methods
Population-based Cooperative Health Research in the Region of Augsburg (KORA) S4-Survey (N = 4,028) was investigated for prognostic value of PLA1A2-polymorphism regarding all-cause mortality, correlation with HbA1c, and mean platelet volume. Multivariate analysis was performed to investigate association between genotype and key variables.
Prevalence of thrombogenic allele variant PLA2 was 15.0%. Multivariate analysis revealed no association between PLA1A2 polymorphism and mortality in the KORA-cohort. HbA1c was a prognostic marker of mortality in non-diabetic persons resulting in J-shaped risk curve with dip at HbA1c = 5.5% (37 mmol/mol), confirming previous findings regarding aged KORA-S4 participants (55–75 years). PLA1A2 was significantly associated with elevated HbA1c levels in diabetic patients (N = 209) and reduced mean platelet volume in general population. In non-diabetic participants (N = 3,819), carriers of PLA2 allele variant presenting with HbA1c > 5.5% (37 mmol/mol) showed higher relative risk of mortality with increasing HbA1c.
PLA1A2 polymorphism is associated with mortality in participants with HbA1c ranging from 5.5% (37 mmol/mol) to 6.5% (48 mmol/mol). Maintenance of euglycemic control and antiplatelet therapy are therefore regarded as effective primary prevention in this group.
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
In many European cities mass concentrations of PM10 (particles less than 10 microm in size) are still exceeding air quality standards as set by the European Commission in 1999. As a consequence, many cities introduced low emission zones (LEZs) to improve air quality and to meet the limit values. In Germany currently 48 LEZs are in operation. By means of dispersion modeling, PM10 concentrations were estimated to decrease up to 10%. Analysis of PM10 levels conducted for Cologne, Berlin, and Munich some time after the LEZs were introduced showed reduction of PM10 mass concentration in the estimated range. The PM10 particle fraction is, however composed of particles with varying toxicity, of which diesel soot is highly health relevant. An evaluation of air quality data conducted in Berlin showed that in 2010 traffic-related soot concentrations measured along major roads decreased by 52% compared to 2007. Diesel particle emissions in Berlin were reduced in 2012 by 63% compared to a business-as-usual scenario (reference year 2007). A strong reduction of the traffic-related particle fraction of PM2.5 was also reported for Munich. Therefore, it is likely that the effects of LEZs are considerably more significant to human health than was anticipated when only considering the reduction of PM10 mass concentrations.
The implementation of low emission zones in German cities might result in a reduction of PM10 levels concentrations by up to 10%. However, it is difficult to show a reduction of PM10 annual averages in this order of magnitude as meteorology has a large impact on the year-to-year variation of PM mass concentrations. Monitoring of other PM metrics such as black smoke (BS) or elemental carbon (EC) might be a better strategy for evaluating LEZs effects. The benefit of low emission zones on human health is far greater than is presently visible from routine measurements of PM10.
Journal of the Air & Waste Management Association (1995) 04/2014; 64(4):481-7. DOI:10.1080/10962247.2013.868380 · 1.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Wellcome Trust Case Control Consortium 3 anorexia nervosa genome-wide association scan includes 2907 cases from 15 different populations of European origin genotyped on the Illumina 670K chip. We compared methods for identifying population stratification, and suggest list of markers that may help to counter this problem. It is usual to identify population structure in such studies using only common variants with minor allele frequency (MAF) >5%; we find that this may result in highly informative SNPs being discarded, and suggest that instead all SNPs with MAF >1% may be used. We established informative axes of variation identified via principal component analysis and highlight important features of the genetic structure of diverse European-descent populations, some studied for the first time at this scale. Finally, we investigated the substructure within each of these 15 populations and identified SNPs that help capture hidden stratification. This work can provide information regarding the designing and interpretation of association results in the International Consortia
European Journal of HumanGenetics 02/2014; 22(10). DOI:10.1038/ejhg.2014.1. · 4.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case–control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28–1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32–1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93–1.64, 155/120 cases/controls) in hospital-based studies.
There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42–1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44–2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95–1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos.
International Journal of Cancer 01/2014; 136(2). DOI:10.1002/ijc.28986 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P < 5 x 10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.
[Show abstract][Hide abstract] ABSTRACT: A link between severe mental stress and shorter telomere length (TL) has been suggested. We analysed the impact of Posttraumatic Stress Disorder (PTSD) on TL in the general population and postulated a dose-dependent TL association in subjects suffering from partial PTSD compared to full PTSD.
Data are derived from the population-based KORA F4 study (2006-2008), located in southern Germany including 3,000 individuals (1,449 men and 1,551 women) with valid and complete TL data. Leukocyte TL was measured using a quantitative PCR-based technique. PTSD was assessed in a structured interview and by applying the Posttraumatic Diagnostic Scale (PDS) and the Impact of Event Scale (IES). A total of 262 (8.7%) subjects qualified for having partial PTSD and 51 (1.7%) for full PTSD. To assess the association of PTSD with the average TL, linear regression analyses with adjustments for potential confounding factors were performed.
The multiple model revealed a significant association between partial PTSD and TL (beta = -0.051, p = 0.009) as well as between full PTSD and shorter TL (beta = -0.103, p = 0.014) indicating shorter TL on average for partial and full PTSD. An additional adjustment for depression and depressed mood/exhaustion gave comparable beta estimations.
Participants with partial and full PTSD had significantly shorter leukocyte TL than participants without PTSD. The dose-dependent variation in TL of subjects with partial and full PTSD exceeded the chronological age effect, and was equivalent to an estimated 5 years in partial and 10 years in full PTSD of premature aging.
PLoS ONE 07/2013; 8(7):e64762. DOI:10.1371/journal.pone.0064762 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals
and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913,
rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R2 ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2%
of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been
associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement
of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates
can anchor power analyses in social-science genetics.