Manja Koch

Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota

Human gut microbiota is an important determinant for health and disease, and recent studies emphasize the numerous factors shaping its diversity. Here we performed a genome-wide association study (GWAS) of the gut microbiota using two cohorts from northern Germany totaling 1,812 individuals. Comprehensively controlling for diet and non-genetic parameters, we identify genome-wide significant associations for overall microbial variation and individual taxa at multiple genetic loci, including the VDR gene (encoding vitamin D receptor). We observe significant shifts in the microbiota of Vdr−/− mice relative to control mice and correlations between the microbiota and serum measurements of selected bile and fatty acids in humans, including known ligands and downstream metabolites of VDR. Genome-wide significant (P < 5 × 10−8) associations at multiple additional loci identify other important points of host–microbe intersection, notably several disease susceptibility genes and sterol metabolism pathway components. Non-genetic and genetic factors each account for approximately 10% of the variation in gut microbiota, whereby individual effects are relatively small.

Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures

Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4.185) and a prospective cohort of German Health Insurance beneficiaries (n=1.811.098). A potential genetic overlap was explored using genome-wide data from >22.000 coronary artery disease (CAD) and >4.000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3.717 controls. Controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odd’s ratio OR=2.36; 95% confidence interval CI=1.26–4.41) and myocardial infarction (MI, OR=2.26, 95% CI=1.03–4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk RR=1.11; 95%CI=1.08–1.14) and MI (RR=1.14; 95%CI=1.06–1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the MHC, there was no evidence for genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct.

Comparison of two exploratory dietary patterns in association with the metabolic syndrome in a Northern German population.

Diet is related to many chronic disease conditions such as the metabolic syndrome (MetS). We set out to compare behaviour-related with disease-related patterns and their association with the MetS in a German cross-sectional study. A total of 905 participants of a Northern German cohort (aged 25-82 years) completed a FFQ, underwent anthropometric assessments and provided a blood sample. Dietary patterns were derived by principal component analysis (PCA) and reduced-rank regression (RRR) from forty-two food groups. Components of the MetS were used as response variables for the RRR analysis. Simplified patterns comprising ten food groups were generated. Logistic regression analysis was performed to evaluate the likelihood of having the MetS across the quartiles of simplified pattern scores. We identified two similar dietary patterns derived by PCA and RRR characterised by high intakes of potatoes, various vegetables, red and processed meat, fats, sauce and bouillon. Comparing simplified patterns, an increased RRR pattern score was associated with a higher OR (2·18, 95% CI 1·25, 3·81) of having the MetS than an increased PCA pattern score (OR 1·92, 95% CI 1·21, 3·03). Comparing concordant food groups by both dietary pattern methods, a diet high in legumes, beef, processed meat and bouillon was also positively associated with the prevalence of the MetS after adjustment for potential confounders (OR 1·71, 95% CI 1·04, 2·79). We identified a behaviour-related pattern that was positively associated with the MetS. The application of both dietary pattern methods may be advantageous to obtain information for designing and realising dietary guidelines. Prospective studies are needed to confirm the results.

Dietary patterns associated with magnetic resonance imaging–determined liver fat content in a general population study

BACKGROUND The association between diet and fatty liver disease (FLD) has predominantly been analyzed for single nutrients or foods, and findings have been inconsistent. OBJECTIVE We aimed to compare associations of hypothesis-driven and exploratory dietary pattern scores with liver fat content. DESIGN Liver fat was measured by using magnetic resonance imaging as liver signal intensity (LSI) in a population-based, cross-sectional study that included 354 individuals. We applied partial least-squares regression to derive an exploratory dietary pattern score that explained variation in both the intake of 38 food groups, which were assessed by using a food-frequency questionnaire, and LSI. The hypothesis-driven score was calculated on the basis of published studies. Multivariable linear or logistic regression was used to investigate associations between dietary pattern scores and LSI or FLD. RESULTS A higher percentage of LSI variation was explained by the exploratory (12.6%) compared with the hypothesis-driven (2.2%) dietary pattern. Of the 13 most important food groups of the exploratory dietary pattern, intakes of green and black tea, soups, and beer were also individually associated with LSI values. A 1-unit increase in the exploratory dietary pattern score was positively associated with FLD (OR: 1.56; 95% CI: 1.29, 1.88). Furthermore, a 1-unit increase in the hypothesis-driven dietary pattern score, which consisted of alcohol, soft drinks, meat, coffee, and tea, was positively associated with FLD (OR: 1.25; 95% CI: 1.10, 1.43). CONCLUSION We defined a hypothesis-driven dietary pattern and derived an exploratory dietary pattern, both of which included alcohol, meat (poultry), and tea, associated with liver fat content independent from confounders, which should be explored in prospective studies.

Body weight gain and risk of colorectal cancer: a systematic review and meta-analysis of observational studies

While the relationship between body mass index as an indicator of excess body weight and the risk of colorectal cancer (CRC) is well established, the association between body weight gain in adulthood and risk of CRC remains unresolved. We quantified this association in a meta‐analysis of 12 observational studies published until November 2014 with a total of 16,151 incident CRC cases. Random effect models were used to obtain summary relative risks (RR) and 95% confidence intervals (95% CIs). Between‐study heterogeneity was assessed using I2 statistics. Overall, the summary RR (95% CI) was 1.22 (1.14–1.30) for high body weight gain (midpoint: 15.2 kg) compared with stable weight (P for heterogeneity = 0.182; I2 = 21.2%). In a dose‐response analysis, each 5 kg weight gain was associated with a 4% (95% CI: 2%–5%) higher risk of CRC. The association persisted after adjustment for body weight at younger age and was present for both men and women, as well as for colon and rectal cancer. Differences by sex were detected for colon cancer (P for interaction = 0.003, with higher risk for men than women), but not for rectal cancer (P for interaction = 0.613). In conclusion, these data underscore the importance of body weight management from early adulthood onwards for the prevention of CRC development.

MRI-determined total volumes of visceral and subcutaneous abdominal and trunk adipose tissue are differentially and sex-dependently associated with patterns of estimated usual nutrient intake in a northern German population

BACKGROUND Visceral (VAT) and subcutaneous abdominal (SAAT) and trunk (STRAT) adipose tissue (AT) have been suggested to be differentially influenced by diet. OBJECTIVE We investigated whether and to what extent usual patterns of nutrient intake are associated with VAT, SAAT, and STRAT compared with nondietary predictors in northern German adults (n = 583). DESIGN AT volumes were quantified by magnetic resonance imaging. Nutrient intake was estimated by a 112-item food-frequency questionnaire linked to the German Food Code and Nutrient Database. Exploratory nutrient patterns were derived by principal components analysis (PCA) and partial least-squares regression (PLS) of 87 nutrients. Cross-sectional associations between nutrient patterns, single nutrients, or total energy intake and AT compartments were analyzed by multiple linear regression. RESULTS Next to sex and age, respectively, which were important nondietary predictors and accounted for more of the variation in VAT (∼13% and ∼4%) than in SAAT or STRAT (both 4-7% and <1%), variation in VAT (16.8% or 17.6%) was explained to a greater extent by 9 or 2 nutrient patterns derived by principal components analysis or partial least-squares regression, respectively, than was variation in SAAT (10.6% or 8.2%) or STRAT (11.5% or 8.6%). Whereas VAT (16.6%) was primarily explained by nutrient quality, SAAT (6.9%) and STRAT (7.4%) were mainly explained by total energy intake. VAT was positively associated with nutrients characteristic of animal (except for dairy) products, including arachidonic acid (standardized β: 0.25; 95% CI: 0.15, 0.34; P < 0.0001), but negatively with dietary fiber, including polypentoses (standardized β: -0.17; 95% CI: -0.24, -0.09; P < 0.0001), and nutrients found in milk. The direction and strength of many associations, however, depended strongly on sex and adjustment for BMI. CONCLUSION VAT may be particularly associated with sex-specific interplays of nutrients found in animal products and fiber, whereas SAAT and STRAT are associated with total energy intake.

HDL-cholesterol and apolipoproteins in relation to dementia.

Purpose of review Dementia is a major cause of disability and institutionalization. Apart from age and apolipoprotein E (APOE) genotype, there are currently no established, clinically relevant, noninvasive markers of dementia. We conducted a literature search of recent observational epidemiological studies evaluating the relevance of HDL cholesterol (HDL-C) and apolipoproteins as biomarkers of future and prevalent risk of dementia. Recent findings HDL-C and apolipoproteins, such as apoE have been suggested to play important roles in brain function and have been associated with dementia and Alzheimers disease in observational studies. However, findings have been inconsistent, especially across study designs. In recent years, modern proteomic approaches have enabled the investigation of further apolipoproteins involved in the deposition and clearance of &bgr;-amyloid, a determining factor for subsequent neurodegeneration. Summary Associations in cross-sectional studies are not always indicative of a prospective relationship. Large studies find that plasma HDL-C and apoE are inversely associated with dementia. Higher apoJ levels might be a marker of prevalent dementia, but were not associated with risk of future dementia. The investigation of HDL-C and apolipoproteins in relation to dementia represents an area of opportunity. Additional prospective studies that account for potential confounding factors and that explore potential effect modifiers such as APOE genotype and sex are needed to fully investigate the potential of these noninvasive measures in disease prediction.

Light to Moderate Alcohol Consumption Is Associated With Lower Risk of Aortic Valve Sclerosis

Objective— In developed countries, sclerotic and calcific degeneration of the aortic valve is a common disorder showing pathophysiologic similarities with atherothrombotic coronary disease. Light to moderate alcohol consumption has been associated with a lower risk for atherothrombotic coronary disease and mortality. Whether alcohol consumption affects the development of aortic valve sclerosis (AVS) is not well known. In the present study, we aim to analyze the cross-sectional association between average daily alcohol consumption and AVS in the general population. Approach and Results— We analyzed cross-sectional data from 2022 men and women, aged 45 to 81 years, from the population-based Study of Health in Pomerania. We used a computer-assisted interview that included beverage-specific questions about quantity and frequency of alcohol over the last 30 days to calculate the average quantity of alcohol consumption (in grams of ethanol per day). AVS was ascertained by echocardiography. The prevalence of AVS was 32.3%. Average daily alcohol intake displayed a J-type relation with AVS (fully adjusted P value: 0.005). Compared with individuals with an average consumption of 10 g of alcohol per day, multivariable-adjusted odds ratios were 1.60 (95% confidence interval, 1.19–2.14) among current abstainers and 1.56 (95% confidence interval, 1.01–2.41) among individuals with an average consumption of 60 g per day. Conclusions— Our findings indicate that light to moderate alcohol consumption was associated with a lower odd of having AVS. Prospective data need to address whether alcohol consumption and related changes over time in several biological markers affect the progression of AVS.

Light to Moderate Alcohol Consumption Is Associated With Lower Risk of Aortic Valve Sclerosis: The Study of Health in Pomerania (SHIP)

Objective— In developed countries, sclerotic and calcific degeneration of the aortic valve is a common disorder showing pathophysiologic similarities with atherothrombotic coronary disease. Light to moderate alcohol consumption has been associated with a lower risk for atherothrombotic coronary disease and mortality. Whether alcohol consumption affects the development of aortic valve sclerosis (AVS) is not well known. In the present study, we aim to analyze the cross-sectional association between average daily alcohol consumption and AVS in the general population. Approach and Results— We analyzed cross-sectional data from 2022 men and women, aged 45 to 81 years, from the population-based Study of Health in Pomerania. We used a computer-assisted interview that included beverage-specific questions about quantity and frequency of alcohol over the last 30 days to calculate the average quantity of alcohol consumption (in grams of ethanol per day). AVS was ascertained by echocardiography. The prevalence of AVS was 32.3%. Average daily alcohol intake displayed a J-type relation with AVS (fully adjusted P value: 0.005). Compared with individuals with an average consumption of 10 g of alcohol per day, multivariable-adjusted odds ratios were 1.60 (95% confidence interval, 1.19–2.14) among current abstainers and 1.56 (95% confidence interval, 1.01–2.41) among individuals with an average consumption of 60 g per day. Conclusions— Our findings indicate that light to moderate alcohol consumption was associated with a lower odd of having AVS. Prospective data need to address whether alcohol consumption and related changes over time in several biological markers affect the progression of AVS.

Dietary patterns and fatty liver disease.

Purpose of review The association of dietary intake and fatty liver disease (FLD) is of importance for disease prevention. Dietary pattern analysis enables the investigation of overall diet and permits to take interactions and cumulative effects of dietary components into account. This review summarizes recent findings on the association of dietary patterns and FLD. Recent findings A systematic review of articles published from March 2013 to August 2014 identified four relevant observational (n = 116–995) and one interventional study (n = 12). The Healthy Eating Index and Dietary Diversity Scores were not related to nonalcoholic FLD. A Mediterranean diet intervention resulted in a significant decrease in liver fat content over 6 weeks. Exploratory approaches revealed a ‘Western pattern’ and a pattern having alcohol, meat (poultry) and tea in common with a hypothesis-driven pattern, which were both associated with FLD. Summary Most studies were limited by a cross-sectional design and small-to-moderate sample sizes. Observational studies applying exploratory approaches and a Mediterranean diet intervention demonstrated most promising results relating dietary patterns to FLD. Prospective studies with measurement of liver fat on a continuous scale at multiple time points in large samples are important requisites to improve our understanding of FLD cause.