@article{KroegerMeidtnerStefanetal.2018, author = {Kroeger, Janine and Meidtner, Karina and Stefan, Norbert and Guevara, Marcela and Kerrison, Nicola D. and Ardanaz, Eva and Aune, Dagfinn and Boeing, Heiner and Dorronsoro, Miren and Dow, Courtney and Fagherazzi, Guy and Franks, Paul W. and Freisling, Heinz and Gunter, Marc J. and Maria Huerta, Jose and Kaaks, Rudolf and Key, Timothy J. and Khaw, Kay Tee and Krogh, Vittorio and Kuehn, Tilman and Mancini, Francesca Romana and Mattiello, Amalia and Nilsson, Peter M. and Olsen, Anja and Overvad, Kim and Palli, Domenico and Ramon Quiros, J. and Rolandsson, Olov and Sacerdote, Carlotta and Sala, Nuria and Salamanca-Fernandez, Elena and Sluijs, Ivonne and Spijkerman, Annemieke M. W. and Tjonneland, Anne and Tsilidis, Konstantinos K. and Tumino, Rosario and van der Schouw, Yvonne T. and Forouhi, Nita G. and Sharp, Stephen J. and Langenberg, Claudia and Riboli, Elio and Schulze, Matthias B. and Wareham, Nicholas J.}, title = {Circulating Fetuin-A and Risk of Type 2 Diabetes}, series = {Diabetes : a journal of the American Diabetes Association}, volume = {67}, journal = {Diabetes : a journal of the American Diabetes Association}, number = {6}, publisher = {American Diabetes Association}, address = {Alexandria}, issn = {0012-1797}, doi = {10.2337/db17-1268}, pages = {1200 -- 1205}, year = {2018}, abstract = {Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28\% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95\% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.}, language = {en} } @article{GalbeteKroegerJannaschetal.2018, author = {Galbete, Cecilia and Kr{\"o}ger, Janine and Jannasch, Franziska and Iqbal, Khalid and Schwingshackl, Lukas and Schwedhelm, Carolina and Weikert, Cornelia and Boeing, Heiner and Schulze, Matthias Bernd}, title = {Nordic diet, Mediterranean diet, and the risk of chronic diseases}, series = {BMC Medicine}, volume = {16}, journal = {BMC Medicine}, publisher = {BMC}, address = {London}, issn = {1741-7015}, doi = {10.1186/s12916-018-1082-y}, pages = {13}, year = {2018}, abstract = {Background: The Mediterranean Diet (MedDiet) has been acknowledged as a healthy diet. However, its relation with risk of major chronic diseases in non-Mediterranean countries is inconclusive. The Nordic diet is proposed as an alternative across Northern Europe, although its associations with the risk of chronic diseases remain controversial. We aimed to investigate the association between the Nordic diet and the MedDiet with the risk of chronic disease (type 2 diabetes (T2D), myocardial infarction (MI), stroke, and cancer) in the EPIC-Potsdam cohort. Methods: The EPIC-Potsdam cohort recruited 27,548 participants between 1994 and 1998. After exclusion of prevalent cases, we evaluated baseline adherence to a score reflecting the Nordic diet and two MedDiet scores (tMDS, reflecting the traditional MedDiet score, and the MedPyr score, reflecting the MedDiet Pyramid). Cox regression models were applied to examine the association between the diet scores and the incidence of major chronic diseases. Results: During a follow-up of 10.6 years, 1376 cases of T2D, 312 of MI, 321 of stroke, and 1618 of cancer were identified. The Nordic diet showed a statistically non-significant inverse association with incidence of MI in the overall population and of stroke in men. Adherence to the MedDiet was associated with lower incidence of T2D (HR per 1 SD 0.93, 95\% CI 0.88-0.98 for the tMDS score and 0.92, 0.87-0.97 for the MedPyr score). In women, the MedPyr score was also inversely associated with MI. No association was observed for any of the scores with cancer. Conclusions: In the EPIC-Potsdam cohort, the Nordic diet showed a possible beneficial effect on MI in the overall population and for stroke in men, while both scores reflecting the MedDiet conferred lower risk of T2D in the overall population and of MI in women.}, language = {en} } @article{LiStomaLottaetal.2020, author = {Li, Chen and Stoma, Svetlana and Lotta, Luca A. and Warner, Sophie and Albrecht, Eva and Allione, Alessandra and Arp, Pascal P. and Broer, Linda and Buxton, Jessica L. and Boeing, Heiner and Langenberg, Claudia and Codd, Veryan}, title = {Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length}, series = {American Journal of Human Genetics}, volume = {106}, journal = {American Journal of Human Genetics}, number = {3}, publisher = {Elsevier}, address = {Amsterdam}, pages = {16}, year = {2020}, abstract = {Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.}, language = {en} } @article{SchwingshacklRuzanskaAntonetal.2018, author = {Schwingshackl, Lukas and Ruzanska, Ulrike Alexandra and Anton, Verena and Wallroth, Raphael and Ohla, Kathrin and Knueppel, Sven and Schulze, Matthias Bernd and Pischon, Tobias and Deutschbein, Johannes and Schenk, Liane and Warschburger, Petra and Harttig, Ulrich and Boeing, Heiner and Bergmann, Manuela M.}, title = {The NutriAct Family Study: a web-based prospective study on the epidemiological, psychological and sociological basis of food choice}, series = {BMC public health}, volume = {18}, journal = {BMC public health}, publisher = {BMC}, address = {London}, issn = {1471-2458}, doi = {10.1186/s12889-018-5814-x}, pages = {12}, year = {2018}, abstract = {Background: Most studies on food choice have been focussing on the individual level but familial aspects may also play an important role. This paper reports of a novel study that will focus on the familial aspects of the formation of food choice among men and women aged 50-70 years by recruiting spouses and siblings (NutriAct Family Study; NFS). Discussion: Until August 4th 2017, 4783 EPIC-Participants were contacted by mail of which 446 persons recruited 2 to 5 family members (including themselves) resulting in 1032 participants, of whom 82\% had started answering or already completed the questionnaires. Of the 4337 remaining EPIC-participants who had been contacted, 1040 (24\%) did not respond at all, and 3297 (76\%) responded but declined, in 51\% of the cases because of the request to recruit at least 2 family members in the respective age range. The developed recruitment procedures and web-based methods of data collection are capable to generate the required study population including the data on individual and inter-personal determinants which will be linkable to food choice. The information on familial links among the study participants will show the role of familial traits in midlife for the adoption of food choices supporting healthy aging.}, language = {en} } @article{WittenbecherOuniKuxhausetal.2019, author = {Wittenbecher, Clemens and Ouni, Meriem and Kuxhaus, Olga and J{\"a}hnert, Markus and Gottmann, Pascal and Teichmann, Andrea and Meidtner, Karina and Kriebel, Jennifer and Grallert, Harald and Pischon, Tobias and Boeing, Heiner and Schulze, Matthias Bernd and Sch{\"u}rmann, Annette}, title = {Insulin-Like Growth Factor Binding Protein 2 (IGFBP-2) and the Risk of Developing Type 2 Diabetes}, series = {Diabetes : a journal of the American Diabetes Association}, volume = {68}, journal = {Diabetes : a journal of the American Diabetes Association}, number = {1}, publisher = {American Diabetes Association}, address = {Alexandria}, issn = {0012-1797}, doi = {10.2337/db18-0620}, pages = {188 -- 197}, year = {2019}, abstract = {Recent studies suggest that insulin-like growth factor binding protein 2 (IGFBP-2) may protect against type 2 diabetes, but population-based human studies are scarce. We aimed to investigate the prospective association of circulating IGFBP-2 concentrations and of differential methylation in the IGFBP-2 gene with type 2 diabetes risk.}, language = {en} } @article{EichelmannSchulzeWittenbecheretal.2019, author = {Eichelmann, Fabian and Schulze, Matthias Bernd and Wittenbecher, Clemens and Menzel, Juliane and Weikert, Cornelia and di Giuseppe, Romina and Biemann, Ronald and Isermann, Berend and Fritsche, Andreas and Boeing, Heiner and Aleksandrova, Krasimira}, title = {Association of Chemerin Plasma Concentration With Risk of Colorectal Cancer}, series = {JAMA network open}, volume = {2}, journal = {JAMA network open}, number = {3}, publisher = {American Veterinary Medical Association}, address = {Chicago}, issn = {2574-3805}, doi = {10.1001/jamanetworkopen.2019.0896}, pages = {14}, year = {2019}, abstract = {IMPORTANCE Inflammatory processes have been suggested to have an important role in colorectal cancer (CRC) etiology. Chemerin is a recently discovered inflammatory biomarker thought to exert chemotactic, adipogenic, and angiogenic functions. However, its potential link with CRC has not been sufficiently explored. OBJECTIVE To evaluate the prospective association of circulating plasma chemerin concentrations with incident CRC. DESIGN, SETTING, AND PARTICIPANTS Prospective case-cohort study based on 27 548 initially healthy participants from the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort who were followed for up to 16 years. Baseline study information and samples were collected between August 23, 1994, and September 25, 1998. Recruitment was according to random registry sampling from the geographical area of Potsdam, Germany, and surrounding municipalities. The last date of study follow-up was May 10, 2010. Statistical analysis was conducted in 2018. MAIN OUTCOMES AND MEASURES Incident CRC, colon cancer, and rectal cancer. Baseline chemerin plasma concentrations were measured by enzyme-linked immunosorbent assay. CONCLUSIONS AND RELEVANCE This study found that the association between chemerin concentration and the risk of incident CRC was linear and independent of established CRC risk factors. Further studies are warranted to evaluate chemerin as a novel immune-inflammatory agent in colorectal carcinogenesis.}, language = {en} } @article{JannaschKroegerAgnolietal.2019, author = {Jannasch, Franziska and Kr{\"o}ger, Janine and Agnoli, Claudia and Barricarte, Aurelio and Boeing, Heiner and Cayssials, Val{\´e}rie and Colorado-Yohar, Sandra and Dahm, Christina C. and Dow, Courtney and Fagherazzi, Guy and Franks, Paul W. and Freisling, Heinz and Gunter, Marc J. and Kerrison, Nicola D. and Key, Timothy J. and Khaw, Kay-Tee and K{\"u}hn, Tilman and Kyro, Cecilie and Mancini, Francesca Romana and Mokoroa, Olatz and Nilsson, Peter and Overvad, Kim and Palli, Domenico and Panico, Salvatore and Quiros Garcia, Jose Ramon and Rolandsson, Olov and Sacerdote, Carlotta and Sanchez, Maria-Jose and Sahrai, Mohammad Sediq and Sch{\"u}bel, Ruth and Sluijs, Ivonne and Spijkerman, Annemieke M. W. and Tjonneland, Anne and Tong, Tammy Y. N. and Tumino, Rosario and Riboli, Elio and Langenberg, Claudia and Sharp, Stephen J. and Forouhi, Nita G. and Schulze, Matthias Bernd and Wareham, Nicholas J.}, title = {Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations}, series = {The Journal of Nutrition}, volume = {149}, journal = {The Journal of Nutrition}, number = {6}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0022-3166}, doi = {10.1093/jn/nxz031}, pages = {1047 -- 1055}, year = {2019}, abstract = {Background: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence. Objective: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries. Methods: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association. Results: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95\% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95\% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95\% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea. Conclusions: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.}, language = {en} } @article{WittenbecherKuxhausBoeingetal.2019, author = {Wittenbecher, Clemens and Kuxhaus, Olga and Boeing, Heiner and Stefan, Norbert and Schulze, Matthias Bernd}, title = {Associations of short stature and components of height with incidence of type 2 diabetes}, series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, volume = {62}, journal = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, number = {12}, publisher = {Springer}, address = {New York}, issn = {0012-186X}, doi = {10.1007/s00125-019-04978-8}, pages = {2211 -- 2221}, year = {2019}, abstract = {Aims/hypothesis This study aimed to evaluate associations of height as well as components of height (sitting height and leg length) with risk of type 2 diabetes and to explore to what extent associations are explainable by liver fat and cardiometabolic risk markers. Methods A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 26,437 participants who provided blood samples was designed. We randomly selected a subcohort of 2500 individuals (2029 diabetes-free at baseline and with anamnestic, anthropometrical and metabolic data for analysis). Of the 820 incident diabetes cases identified in the full cohort during 7 years of follow-up, 698 remained for analyses after similar exclusions. Results After adjustment for age, potential lifestyle confounders, education and waist circumference, greater height was related to lower diabetes risk (HR per 10 cm, men 0.59 [95\% CI 0.47, 0.75] and women 0.67 [0.51, 0.88], respectively). Leg length was related to lower risk among men and women, but only among men if adjusted for total height. Adjustment for liver fat and triacylglycerols, adiponectin and C-reactive protein substantially attenuated associations between height and diabetes risk, particularly among women. Conclusions/interpretation We observed inverse associations between height and risk of type 2 diabetes, which was largely related to leg length among men. The inverse associations may be partly driven by lower liver fat content and a more favourable cardiometabolic profile.}, language = {en} } @article{MuehlenbruchKuxhausPencinaetal.2015, author = {M{\"u}hlenbruch, Kristin and Kuxhaus, Olga and Pencina, Michael J. and Boeing, Heiner and Liero, Hannelore and Schulze, Matthias Bernd}, title = {A confidence ellipse for the Net Reclassification Improvement}, series = {European journal of epidemiology}, volume = {30}, journal = {European journal of epidemiology}, number = {4}, publisher = {Springer}, address = {Dordrecht}, issn = {0393-2990}, doi = {10.1007/s10654-015-0001-1}, pages = {299 -- 304}, year = {2015}, abstract = {The Net Reclassification Improvement (NRI) has become a popular metric for evaluating improvement in disease prediction models through the past years. The concept is relatively straightforward but usage and interpretation has been different across studies. While no thresholds exist for evaluating the degree of improvement, many studies have relied solely on the significance of the NRI estimate. However, recent studies recommend that statistical testing with the NRI should be avoided. We propose using confidence ellipses around the estimated values of event and non-event NRIs which might provide the best measure of variability around the point estimates. Our developments are illustrated using practical examples from EPIC-Potsdam study.}, language = {en} }