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Non-replication of an association of CTNNBL1 polymorphisms and obesity in a population of Central European ancestry
Carla IG Vogel, Brandon Greene, André Scherag, Timo D Müller, Susann Friedel, Harald Grallert, Iris M Heid, Thomas Illig, H-Erich Wichmann, Helmut Sch?fer, Johannes Hebebrand, Anke Hinney
BMC Medical Genetics , 2009, DOI: 10.1186/1471-2350-10-14
Abstract: The GWA studies were carried out using Affymetrix? SNP Chips with approximately 500,000 markers each. In the families, SNP rs6013029 was genotyped using the TaqMan? allelic discrimination assay. The German case-control GWA included 487 extremely obese children and adolescents and 442 healthy lean individuals. The adult GWA included 1,644 individuals from a German population-based study (KORA). The 775 independent German families consisted of extremely obese children and adolescents and their parents.We found no evidence for an association of the reported variants in CTNNBL1 with early onset obesity or increased BMI. Further, in our family-based study we found no evidence for over-transmission of the rs6013029 risk-allele T to obese children. Additionally, we found no evidence for an association of SH3PXD2B, SLIT3 and FLJ42133 variants in our two GWA samples.We detected no confirmation of the recent association of variants in CTNNBL1 with obesity in a population of Central European ancestry.Obesity is a major health problem worldwide and results from an interplay of social, environmental and genetic factors [1]. Genome-wide association (GWA) studies have contributed to the identification of new polygenic variants contributing to inter-individual body mass index (BMI) differences [2-5]. Recently, Liu et al. [6] reported that variants in the beta catenin-like 1 gene (CTNNBL1) were associated with increased fat mass and obesity in a GWA conducted with 1,000 adult U.S. Caucasians. In the same report, this observation was validated in a French case-control sample (896 class III obese adults; BMI ≥ 40 kg/m2 and 2,916 normal weight controls; BMI < 25 kg/m2).Our study had two objectives. First, we aimed to replicate the association of the obesity risk alleles (rs6013029 T-allele, rs16986921 T-allele, rs6020712 A-allele, rs6020846 G-allele, rs6020395 C-allele, rs16986890 G-allele, rs6096781 C-allele, and rs6020339 C-allele) of CTNNBL1 in two GWA data sets. Second, we explored
Multimorbidity and health-related quality of life in the older population: results from the German KORA-Age study
Matthias Hunger, Barbara Thorand, Michaela Schunk, Angela D?ring, Petra Menn, Annette Peters, Rolf Holle
Health and Quality of Life Outcomes , 2011, DOI: 10.1186/1477-7525-9-53
Abstract: The EQ-5D was administered in the population-based KORA-Age study of 4,565 Germans aged 65 years or older. A generalised additive regression model was used to assess the effects of chronic conditions on HRQL and to account for the nonlinear associations with age and body mass index (BMI). Disease interactions were identified by a forward variable selection method.The conditions with the greatest negative impact on the EQ-5D index were the history of a stroke (regression coefficient -11.3, p < 0.0001) and chronic bronchitis (regression coefficient -8.1, p < 0.0001). Patients with both diabetes and coronary disorders showed more impaired HRQL than could be expected from their separate effects (coefficient of interaction term -8.1, p < 0.0001). A synergistic effect on HRQL was also found for the combination of coronary disorders and stroke. The effect of BMI on the mean EQ-5D index was inverse U-shaped with a maximum at around 24.8 kg/m2.There are important interactions between coronary problems, diabetes mellitus, and the history of a stroke that negatively affect HRQL in the older German population. Not only high but also low BMI is associated with impairments in health status.Multimorbidity, defined as the coexistence of two or more chronic conditions, is a common phenomenon among the older population worldwide: two recent population-based studies indicated that the prevalence of multimorbidity ranges between 40% and 56% in the general population aged 65 years and older [1,2]. Multimorbidity is known to negatively affect health outcomes including mortality, hospitalisation, and readmission [3].Health-related quality of life (HRQL) is a health outcome measure which is increasingly used to assess the medical effectiveness of interventions and to support allocation decisions in the health care sector. Generic HRQL instruments like the EQ-5D are appropriate for non-disease-specific analyses and allow comparisons between patient groups with different medical conditions [
Patterns of Multimorbidity in the Aged Population. Results from the KORA-Age Study  [PDF]
Inge Kirchberger, Christa Meisinger, Margit Heier, Anja-Kerstin Zimmermann, Barbara Thorand, Christine S. Autenrieth, Annette Peters, Karl-Heinz Ladwig, Angela D?ring
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0030556
Abstract: Multimorbidity is a common problem in aged populations with a wide range of individual and societal consequences. The objective of the study was to explore patterns of comorbidity and multimorbidity in an elderly population using different analytical approaches. Data were gathered from the population-based KORA-Age project, which included 4,127 persons aged 65–94 years living in the city of Augsburg and its two surrounding counties in Southern Germany. Information on the presence of 13 chronic conditions was collected in a standardized telephone interview and a self-administered questionnaire. Patterns of comorbidity and multimorbidity were analyzed using prevalence figures, logistic regression models and exploratory tetrachoric factor analysis. The prevalence of multimorbidity (≥2 diseases) was 58.6% in the total sample. Hypertension and diabetes (Odds Ratio [OR] 2.95, 99.58% confidence interval [CI] [2.19–3.96]), as well as hypertension and stroke (OR 2.00, 99.58% CI [1.26–3.16]) most often occurred in combination. This association was independent of age, sex and the presence of other conditions. Using factor analysis, we identified four patterns of multimorbidity: the first pattern includes cardiovascular and metabolic diseases, the second includes joint, liver, lung and eye diseases, the third covers mental and neurologic diseases and the fourth pattern includes gastrointestinal diseases and cancer. 44% of the persons were assigned to at least one of the four multimorbidity patterns; 14% could be assigned to both the cardiovascular/metabolic and the joint/liver/lung/eye pattern. Further common pairs were the mental/neurologic pattern combined with the cardiovascular/metabolic pattern (7.2%) or the joint/liver/lung/eye pattern (5.3%), respectively. Our results confirmed the existence of co-occurrence of certain diseases in elderly persons, which is not caused by chance. Some of the identified patterns of multimorbidity and their overlap may indicate common underlying pathological mechanisms.
Reproductive Factors and Serum Uric Acid Levels in Females from the General Population: The KORA F4 Study  [PDF]
Doris St?ckl, Angela D?ring, Barbara Thorand, Margit Heier, Petra Belcredi, Christa Meisinger
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032668
Abstract: Objective Hyperuricemia is associated with an increased risk of metabolic and cardiovascular diseases. There are pronounced sex differences in the levels of uric acid. It is largely unknown whether or not reproductive parameters which induce hormonal changes are responsible for this. We examined if there are associations between reproductive parameters and uric acid levels in a female population-based sample. Methods In this cross-sectional analysis, data of 1530 women aged 32 to 81 years participating in the KORA F4 study, conducted between 2006 and 2008 in Southern Germany were used. Reproductive parameters were obtained by standardized interviews. Uric acid levels were tested by the uricase method. The whole study sample and stratified in pre- and postmenopausal women was analyzed. Results Menopausal status and earlier age at menarche were associated with higher serum uric acid levels (age-adjusted: p-values 0.003, <0.001 respectively; after multivariable adjustment, including BMI: p-values 0.002, 0.036). A history of oral contraceptive use showed an association with uric acid levels only after multivariable adjustment (p-value 0.009). Hot flushes showed an association with uric acid levels only after age-adjustment (p-value 0.038), but lost significance after adding other confounders. Other reproductive factors, including parity, current or ever use of hormone replacement therapy, current use of oral contraceptives, hysterectomy, bilateral oophorectomy, or depressive mood related to menopausal transition were not associated with uric acid levels. Conclusions Postmenopausal status, earlier age at menarche and a history of oral contraceptive use were independently associated with higher serum uric acid concentrations in women from the general population. Further studies, especially longitudinal population-based studies investigating the relationship of female reproductive parameters with uric acid levels are necessary to confirm our findings.
Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA)  [PDF]
Moritz F. Sinner equal contributor,Wibke Reinhard equal contributor,Martina Müller equal contributor,Britt-Maria Beckmann,Eimo Martens,Siegfried Perz,Arne Pfeufer,Janina Winogradow,Klaus Stark,Christa Meisinger,H.-Erich Wichmann,Annette Peters,Günter A. J. Riegger,Gerhard Steinbeck,Christian Hengstenberg equal contributor,Stefan K??b equal contributor
PLOS Medicine , 2010, DOI: 10.1371/journal.pmed.1000314
Abstract: Background Early repolarization pattern (ERP) on electrocardiogram was associated with idiopathic ventricular fibrillation and sudden cardiac arrest in a case-control study and with cardiovascular mortality in a Finnish community-based sample. We sought to determine ERP prevalence and its association with cardiac and all-cause mortality in a large, prospective, population-based case-cohort study (Monitoring of Cardiovascular Diseases and Conditions [MONICA]/KORA [Cooperative Health Research in the Region of Augsburg]) comprised of individuals of Central-European descent. Methods and Findings Electrocardiograms of 1,945 participants aged 35–74 y, representing a source population of 6,213 individuals, were analyzed applying a case-cohort design. Mean follow-up was 18.9 y. Cause of death was ascertained by the 9th revision of the International Classification of Disease (ICD-9) codes as documented in death certificates. ERP-attributable effects on mortality were determined by a weighted Cox proportional hazard model adjusted for covariables. Prevalence of ERP was 13.1% in our study. ERP was associated with cardiac and all-cause mortality, most pronounced in those of younger age and male sex; a clear ERP-age interaction was detected (p = 0.005). Age-stratified analyses showed hazard ratios (HRs) for cardiac mortality of 1.96 (95% confidence interval [CI] 1.05–3.68, p = 0.035) for both sexes and 2.65 (95% CI 1.21–5.83, p = 0.015) for men between 35–54 y. An inferior localization of ERP further increased ERP-attributable cardiac mortality to HRs of 3.15 (95% CI 1.58–6.28, p = 0.001) for both sexes and to 4.27 (95% CI 1.90–9.61, p<0.001) for men between 35–54 y. HRs for all-cause mortality were weaker but reached significance. Conclusions We found a high prevalence of ERP in our population-based cohort of middle-aged individuals. ERP was associated with about a 2- to 4-fold increased risk of cardiac mortality in individuals between 35 and 54 y. An inferior localization of ERP was associated with a particularly increased risk. Please see later in the article for the Editors' Summary
Association between Markers of Fatty Liver Disease and Impaired Glucose Regulation in Men and Women from the General Population: The KORA-F4-Study  [PDF]
Ina-Maria Rückert,Margit Heier,Wolfgang Rathmann,Sebastian E. Baumeister,Angela D?ring,Christa Meisinger
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0022932
Abstract: To investigate whether the elevated liver enzymes gamma-glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate-oxalacetate transaminase (GOT) and alkaline phosphatase (AP) and non-alcoholic fatty liver disease (NAFLD) respectively are independently associated with pre-diabetic states, namely impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or known and newly diagnosed diabetes (NDD), in men and women from the general German population.
Uric Acid Is More Strongly Associated with Impaired Glucose Regulation in Women than in Men from the General Population: The KORA F4-Study  [PDF]
Christa Meisinger, Angela D?ring, Doris St?ckl, Barbara Thorand, Bernd Kowall, Wolfgang Rathmann
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037180
Abstract: Objective High serum uric acid (UA) levels are associated with the metabolic syndrome, type 2 diabetes and cardiovascular disease. It is largely unknown whether there are gender-specific differences regarding the association between UA and prediabetic states. We examined the possible association between UA levels and known as well as newly diagnosed diabetes (NDD), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined IFG/IGT in a population-based sample of 32-to-81-year-old men and women. Research Design and Methods An oral glucose tolerance test was carried out in all 2,740 participants without known diabetes of the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study conducted between 2006 and 2008 in Southern Germany. Serum UA was analysed by the uricase method. Results In women after multivariable adjustment the associations between UA and i-IFG (OR 1.57, 95% CI 1.15–2.14), IFG/IGT (OR 1.52, 1.07–2.16), NDD (OR 1.67, 95% CI 1.28–2.17), and known diabetes (OR 1.47, 95% CI 1.18–1.82) remained significant, but the association with i-IGT (OR 1.14, 95% CI 0.95–1.36) lost significance. In contrast in men, after multivariable adjustment there was only a significant association between UA levels and i-IFG (OR 1.49, 95% CI 1.21–1.84), all other associations were non-significant (i-IGT: OR 1.09, IFG/IGT: OR 1.06, NDD: OR 0.91, known diabetes: OR 1.04; all p-values>0.05). Conclusions Serum UA concentrations were associated with different categories of impaired glucose regulation in individuals from the general population, particularly in women. Further studies investigating the role of UA in the development of derangements in glucose metabolism are needed.
Association of daily tar and nicotine intake with incident myocardial infarction: Results from the population-based MONICA/KORA Augsburg Cohort Study 1984 - 2002
Qiu-Li Zhang, Jens Baumert, Karl-Heinz Ladwig, H-Erich Wichmann, Christa Meisinger, Angela D?ring
BMC Public Health , 2011, DOI: 10.1186/1471-2458-11-273
Abstract: The study was based on 4,099 men and 4,197 women participating in two population-based MONICA Augsburg surveys between 1984 and 1990 and followed up within the KORA framework until 2002. During a mean follow-up of 13.3 years, a number of 307 men and 80 women developed an incident MI event. Relative risks were calculated as hazard ratios (HRs) estimated by Cox proportional hazards models adjusted for cardiovascular risk factors.In the present study, male regular smokers consumed on average more cigarettes per day than female regular smokers (20 versus 15) and had a higher tar and nicotine intake per day. In men, the MI risk compared to never-smokers increased with higher tar intake: HRs were 2.24 (95% CI 1.40-3.56) for 1-129 mg/day, 2.12 (95% CI 1.37-3.29) for 130-259 mg/day and 3.01 (95% CI 2.08-4.36) for ≥ 260 mg/day. In women, the corresponding associations were comparable but more pronounced for high tar intake (HR 4.67, 95% CI 1.76-12.40). Similar associations were observed for nicotine intake.The present study based on a large population-based sample adds important evidence of cumulative effects of tar and nicotine intake on the risk of incident MI. Even low or medium tar and nicotine intake revealed substantial risk increases as compared to never-smokers. Therefore, reduction of tar and nicotine contents in cigarettes cannot be seen as a suitable public health policy in preventing myocardial infarction.Cigarette smoking is a central issue in public health policy as it has been shown to be associated with an elevated risk of various cardiovascular diseases and types of cancer [1,2]. Smoking has been determined as one of the most important risk factors for myocardial infarction (MI) [3-5], but it was shown that smoking cessation can reduce this risk [6]. Many countries and international agencies have made great efforts to change smoking behaviour and to encourage smokers to quit smoking, e.g. by preventing initiation of tobacco use, promoting cessation among ado
SNP and SSR marker analysis and mapping of a maize population
?imi? Domagoj,Leden?an Tatjana,Jambrovi? Antun,Zduni? Zvonimir
Genetika , 2009, DOI: 10.2298/gensr0903237s
Abstract: Although highly polymorphic SSRs are currently the marker of choice worldwide in maize breeding, single nucleotide polymorphisms (SNPs) as a newer marker system are recently used more extensively. The objective of this study was investigate the utility of SSR and SNP markers for mapping of a maize population adapted to conditions of Southeast Europe. Total of 294 F2:3 lines derived from a biparental mapping population were genotyped using 121 polymorphic SNP and SSR markers. The SNP markers were analyzed using the SNPlex technology. 56 of the 142 tested SNPs (39%) were polymorphic between the parents of the mapping population and were successfully mapped. The remaining markers were either not functional (5 = 3.5%) or not polymorphic (81 = 57%). No mapped SNP marker showed more than 10% missing data. On average, the level of missing data for SNPs (1.5%) was considerably lower than that for SSRs (3.4%). For the mapping procedure, the SNP data were combined SSR data. A comparison of the mapping data with the publicly available mapping data on SSR markers and the proprietary mapping data indicates that the map is of good quality and that the map position of almost all markers agrees with their published map position. Thus, information obtained from both marker systems is utilizable for further QTL analysis.
Posttraumatic Stress Disorder and Not Depression Is Associated with Shorter Leukocyte Telomere Length: Findings from 3,000 Participants in the Population-Based KORA F4 Study  [PDF]
Karl-Heinz Ladwig, Anne Catharina Brockhaus, Jens Baumert, Karoline Lukaschek, Rebecca T. Emeny, Johannes Kruse, Veryan Codd, Sibylle H?fner, Eva Albrecht, Thomas Illig, Nilesh J. Samani, H. Erich Wichmann, Christian Gieger, Annette Peters
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064762
Abstract: Background 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. Methods 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. Results 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. Conclusions 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.
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