Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Metabolomics Profile in Depression: A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls
    Bot, Mariska ; Milaneschi, Yuri ; Al-Shehri, Tahani ; Amin, Najaf ; Garmaeva, Sanzhima ; Onderwater, G.L.J. ; Pool, R. ; Thesing, Carisha S. ; Vijfhuizen, Lisanne S. ; Vogelzangs, Nicole ; Arts, Ilja C.W. ; Demirkan, Ayse ; Duijn, Cornelia van; Greevenbroek, Marleen van; Kallen, Carla J.H. van der; Köhler, Sebastian ; Ligthart, Lannie ; Maagdenberg, Arn M.J.M. van den; Mook-Kanamori, Dennis O. ; Mutsert, Renée de; Tiemeier, Henning ; Schram, Miranda T. ; Stehouwer, Coen D.A. ; Terwindt, Gisela M. ; Willems van Dijk, Ko ; Fu, Jingyuan ; Zhernakova, Alexandra ; Beekman, Marian ; Slagboom, Eline ; Boomsma, Dorret I. ; Penninx, Brenda W.J.H. ; Beekman, M. ; Suchiman, H.E.D. ; Deelen, J. ; Amin, N. ; Beulens, J.W. ; Bom, J.A. van der; Bomer, N. ; Demirkan, A. ; Hilten, J.A. van; Meessen, J.M.T.A. ; Pool, R. ; Moed, M.H. ; Fu, J. ; Onderwater, G.L.J. ; Rutters, F. ; Heijden, A.A.W.A. van der; Spek, A. van der; Geleijnse, J.M. ; Jukema, J.W. - \ 2020
    Biological Psychiatry 87 (2020)5. - ISSN 0006-3223 - p. 409 - 418.
    Biomarkers - Cardiovascular - Depression - Metabolites - Metabolomics - Pooled analysis

    Background: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. Methods: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. Results: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q <. 05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. Conclusions: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity.

    Metabolic age based on the BBMRI-NL 1H-NMR metabolomics repository as biomarker of age-related disease
    Akker, Erik B. Van Den; Trompet, Stella ; Barkey Wolf, Jurriaan J.H. ; Beekman, Marian ; Suchiman, H.E.D. ; Deelen, Joris ; Asselbergs, Folkert W. ; Boersma, Eric ; Cats, Davy ; Elders, Petra M. ; Geleijnse, J.M. ; Ikram, M.A. ; Kloppenburg, Margreet ; Mei, Haillang ; Meulenbelt, Ingrid ; Mooijaart, Simon P. ; Nelissen, Rob G.H.H. ; Netea, Mihai G. ; Penninx, Brenda W.J.H. ; Slofstra, Mariska ; Stehouwer, Coen D.A. ; Swertz, Morris A. ; Teunissen, Charlotte E. ; Terwindt, Gisela M. ; T'Hart, Leen M. ; Maagdenberg, Arn M.J.M. Van Den; Harst, Pim Van Der; Horst, Iwan C.C. Van Der; Kallen, Carla J.H. Van Der; Greevenbroek, Marleen M.J. Van; Spil, W.E. Van; Wijmenga, Cisca ; Zhernakova, Alexandra ; Zwinderman, Aeilko H. ; Sattar, Naveed ; Jukema, J.W. ; Duijn, Cornelia M. Van; Boomsma, Dorret I. ; Reinders, Marcel J.T. ; Slagboom, P.E. - \ 2020
    Circulation: Genomic and Precision Medicine 13 (2020). - ISSN 2574-8300 - p. 541 - 547.
    Aging - Cardiovascular disease - Data science - Metabolomics
    BACKGROUND: The blood metabolome incorporates cues from the environment and the host's genetic background, potentially offering a holistic view of an individual's health status. METHODS: We have compiled a vast resource of proton nuclear magnetic resonance metabolomics and phenotypic data encompassing over 25 000 samples derived from 26 community and hospital-based cohorts. RESULTS: Using this resource, we constructed a metabolomics-based age predictor (metaboAge) to calculate an individual's biological age. Exploration in independent cohorts demonstrates that being judged older by one's metabolome, as compared with one's chronological age, confers an increased risk on future cardiovascular disease, mortality, and functionality in older individuals. A web-based tool for calculating metaboAge (metaboage.researchlumc.nl) allows easy incorporation in other epidemiological studies. Access to data can be requested at bbmri.nl/samples-images-data. CONCLUSIONS: In summary, we present a vast resource of metabolomics data and illustrate its merit by constructing a metabolomics-based score for biological age that captures aspects of current and future cardiometabolic health.
    Fortran Standard Library
    Vandenplas, Jeremie ; Aradi, Balint ; Beekman, Izaak ; Certik, Ondrej ; Curcic, Milan ; Buyl, Piere de; Fiol, Juan ; Pribec, Ivan ; Shaffer, Nathaniel - \ 2020
    Food security investments - Transforming the aquaculture, dairy and horticulture sectors in Kenya : Recommendations to support the transition from aid to inclusive aid and trade
    Kessler, J.J. ; Coninx, I. ; Kilelu, C.W. ; Vugt, S.M. van; Koomen, I. ; Bebe, Bockline ; Soma, K. ; Ndambi, O.A. ; Gema, Joyce ; Obwanga, Benson ; Rurangwa, E. ; Moreno Echeverri, I.M. ; Beekman, G. ; Wangui Koge, Jessica ; Lee, Jan van der; Daburon, A.I.L. ; Wesonga, John ; Ruben, R. - \ 2020
    Wageningen Centre for Development Innovation, Wageningen University & Research (WCDI-20-123 ) - 7 p.
    Circulaire uitdagingen : Aanvullende aandachtspunten voor beleid in tijden van kringlooplandbouw
    Dagevos, H. ; Beekman, G. ; Haas, W. de; Lauwere, C.C. de - \ 2020
    Wageningen Economic Research - 12 p.
    circular agriculture - administration - policy - legislation - food policy - agricultural policy - Netherlands - politics
    Cancer-id: Toward identification of cancer by tumor-derived extracellular vesicles in blood
    Rikkert, L.G. ; Beekman, Pepijn ; Caro, J. ; Coumans, F.A.W. ; Enciso-Martinez, A. ; Jenster, G. ; Gac, S. le; Lee, W. ; Leeuwen, T.G. van; Loozen, G.B. ; Nanou, A. ; Nieuwland, R. ; Offerhaus, H.L. ; Otto, C. ; Pegtel, D.M. ; Piontek, M.C. ; Pol, E. van der; Rond, L. de; Roos, W.H. ; Schasfoort, R.B.M. ; Wauben, M.H.M. ; Zuilhof, H. ; Terstappen, L.W.M.M. - \ 2020
    Frontiers in Oncology 10 (2020). - ISSN 2234-943X
    Extracellular vesicles (EVs) have great potential as biomarkers since their composition and concentration in biofluids are disease state dependent and their cargo can contain disease-related information. Large tumor-derived EVs (tdEVs, >1 μm) in blood from cancer patients are associated with poor outcome, and changes in their number can be used to monitor therapy effectiveness. Whereas, small tumor-derived EVs (<1 μm) are likely to outnumber their larger counterparts, thereby offering better statistical significance, identification and quantification of small tdEVs are more challenging. In the blood of cancer patients, a subpopulation of EVs originate from tumor cells, but these EVs are outnumbered by non-EV particles and EVs from other origin. In the Dutch NWO Perspectief Cancer-ID program, we developed and evaluated detection and characterization techniques to distinguish EVs from non-EV particles and other EVs. Despite low signal amplitudes, we identified characteristics of these small tdEVs that may enable the enumeration of small tdEVs and extract relevant information. The insights obtained from Cancer-ID can help to explore the full potential of tdEVs in the clinic.
    Food system analysis of Arua district in Uganda : Working document KB project Improving food systems in less-favoured rural areas of East Africa
    Hengsdijk, Huib ; Roefs, Marlene ; Pereira da Silva, Fatima ; Hermelink, Marleen ; Lee, Jan van der; Deolu-Ajayi, Ayodeji ; Wösten, Henk ; Özkan Gülzari, Seyda ; Pittore, Katherine ; Beekman, Gonne ; Janssen, Valerie ; Alvarez Aranguiz, Adolfo ; Ndambi, Asaah ; Heesmans, Hanneke - \ 2020
    Wageningen : Wageningen University & Research - 50
    Meta-analysis of 3R Kenya findings about the transformation of the aquaculture, dairy and horticulture sectors : Recommendations to support the transition from aid to inclusive aid and trade
    Kessler, Jan Joost ; Coninx, Ingrid ; Kilelu, Catherine ; Vugt, Simone van; Koomen, Irene ; Bebe, Bockline ; Soma, Katrine ; Ndambi, Asaah ; Gema, Joyce ; Obwanga, Benson ; Rurangwa, Eugene ; Moreno Echeverri, Indira ; Beekman, Gonne ; Wangui Koge, Jessica ; Lee, Jan van der; Daburon, Annabelle ; Wesonga, John ; Ruben, Ruerd - \ 2020
    Wageningen : Wageningen Centre for Development Innovation (Report / Wageningen Centre for Development Innovation WCDI-20-116) - 63
    Minilab never misses a tumour
    Beekman, Pepijn - \ 2020
    Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
    Hagenbeek, Fiona A. ; Pool, René ; Dongen, Jenny van; Draisma, H.M. ; Jan Hottenga, Jouke ; Willemsen, Gonneke ; Abdellaoui, Abdel ; Fedko, Iryna O. ; Braber, Anouk den; Visser, Pieter Jelle ; Geus, Eco J.C.N. de; Willems van Dijk, Ko ; Verhoeven, Aswin ; Suchiman, H.E. ; Beekman, Marian ; Slagboom, P.E. ; Duijn, Cornelia M. van; Barkey Wolf, J.J.H. ; Cats, D. ; Amin, N. ; Beulens, J.W. ; Bom, J.A. van der; Bomer, N. ; Demirkan, A. ; Hilten, J.A. van; Meessen, J.M.T.A. ; Moed, M.H. ; Fu, J. ; Onderwater, G.L.J. ; Rutters, F. ; So-Osman, C. ; Flier, W.M. van der; Heijden, A.A.W.A. van der; Spek, A. van der; Asselbergs, F.W. ; Boersma, E. ; Elders, P.M. ; Geleijnse, J.M. ; Ikram, M.A. ; Kloppenburg, M. ; Meulenbelt, I. ; Mooijaart, S.P. ; Nelissen, R.G.H.H. ; Netea, M.G. ; Penninx, B.W.J.H. ; Stehouwer, C.D.A. ; Teunissen, C.E. ; Terwindt, G.M. ; Jukema, J.W. ; Reinders, M.J.T. - \ 2020
    Nature Communications 11 (2020)1. - ISSN 2041-1723

    The original version of the Supplementary Information associated with this Article included an incorrect Supplementary Data 1 file, in which additional delimiters were included in the first column for a number of rows, resulting in column shifts for some of these rows. The HTML has been updated to include a corrected version of Supplementary Data 1; the original incorrect version of Supplementary Data 1 can be found as Supplementary Information associated with this Correction. In addition, the original version of this Article contained an error in the author affiliations. An affiliation of Abdel Abdellaoui with Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

    Lifestyle-Intervention-Induced Reduction of Abdominal Fat Is Reflected by a Decreased Circulating Glycerol Level and an Increased HDL Diameter
    Beekman, Marian ; Schutte, Bianca A.M. ; Akker, Erik B. van den; Noordam, Raymond ; Dibbets-Schneider, Petra ; Geus-Oei, Lioe Fee de; Deelen, Joris ; Rest, Ondine van de; Heemst, Diana van; Feskens, Edith J.M. ; Slagboom, P.E. - \ 2020
    Molecular Nutrition & Food Research 64 (2020)10. - ISSN 1613-4125
    abdominal fat - biomarkers - lifestyle interventions - metabolomics

    Scope: Abdominal obesity is one of the main modifiable risk factors of age-related cardiometabolic disease. Cardiometabolic disease risk and its associated high abdominal fat mass, cholesterol, and glucose concentrations can be reduced by a healthier lifestyle. Hence, the aim is to understand the relation between lifestyle-induced changes in body composition, and specifically abdominal fat, and accompanying changes in circulating metabolic biomarkers. Methods and results: Data from the Growing Old Together (GOTO) study was used, which is a single arm lifestyle intervention in which 164 older adults (mean age 63 years, BMI 23–35 kg/m2) changed their lifestyle during 13 weeks by 12.5% caloric restriction plus 12.5% increase in energy expenditure. It is shown here that levels of circulating metabolic biomarkers, even after adjustment for body mass index, specifically associate with abdominal fat mass. The applied lifestyle intervention mainly reduces abdominal fat mass (−2.6%, SD = 3.0) and this reduction, when adjusted for general weight loss, is highly associated with decreased circulating glycerol concentrations and increased HDL diameter. Conclusion: The lifestyle-induced reduction of abdominal fat mass is particularly associated, independent of body mass index or general weight loss, with decreased circulating glycerol concentrations and increased HDL diameter.

    Beheersen Mcf: niks doen, is geen optie
    Molendijk, Leendert ; Visser, Johnny - \ 2020
    Inundatie effectief tegen chitwoodi
    Molendijk, Leendert - \ 2020
    A data-driven methodology reveals novel myofiber clusters in older human muscles
    Raz, Yotam ; Akker, Erik B. van den; Roest, Tijmen ; Riaz, Muhammad ; Rest, Ondine van de; Suchiman, Eka D. ; Lakenberg, Nico ; Stassen, Stefanie A. ; Putten, Maaike van; Feskens, Edith J.M. ; Reinders, Marcel J.T. ; Goeman, Jelle ; Beekman, Marian ; Raz, Vered ; Slagboom, Pieternella Eline - \ 2020
    FASEB Journal 34 (2020)4. - ISSN 0892-6638 - p. 5525 - 5537.
    bioinformatics - clustering - fibertyping - human - muscle - muscle health - myofiber - myosin heavy chain - RNA-sequencing - sarcomere

    Skeletal muscles control posture, mobility and strength, and influence whole-body metabolism. Muscles are built of different types of myofibers, each having specific metabolic, molecular, and contractile properties. Fiber classification is, therefore, regarded the key for understanding muscle biology, (patho-) physiology. The expression of three myosin heavy chain (MyHC) isoforms, MyHC-1, MyHC-2A, and MyHC-2X, marks myofibers in humans. Typically, myofiber classification is performed by an eye-based histological analysis. This classical approach is insufficient to capture complex fiber classes, expressing more than one MyHC-isoform. We, therefore, developed a methodological procedure for high-throughput characterization of myofibers on the basis of multiple isoforms. The mean fluorescence intensity of the three most abundant MyHC isoforms was measured per myofiber in muscle biopsies of 56 healthy elderly adults, and myofiber classes were identified using computational biology tools. Unsupervised clustering revealed the existence of six distinct myofiber clusters. A comparison with the visual assessment of myofibers using the same images showed that some of these myofiber clusters could not be detected or were frequently misclassified. The presence of these six clusters was reinforced by RNA expressions levels of sarcomeric genes. In addition, one of the clusters, expressing all three MyHC isoforms, correlated with histological measures of muscle health. To conclude, this methodological procedure enables deep characterization of the complex muscle heterogeneity. This study opens opportunities to further investigate myofiber composition in comparative studies.

    Exploring enabling factors for commercializing the aquaculture sector in Kenya
    Obwanga, B. ; Soma, K. ; Ingasia Ayuya, O. ; Rurangwa, E. ; Wonderen, D. van; Beekman, G. ; Kilelu, C. - \ 2020
    Wageningen : Centre for Development Innovation (3R Research report / Centre for Development Innovation 3R Research report 011) - 54 p.
    The aquaculture sector is expanding worldwide, driven by the blue economy and blue growth policy, based on principles of smartness, inclusiveness and sustainability, and the need to provide food and nutrition security to an ever-growing population. This trend is still at an early stage in Kenya. This report explores core enabling factors for commercialization of the aquaculture sector in Kenya, based on a structured household survey and a qualitative literature survey and through application of an analytical food system approach that includes the value chain and consumers. First, nine commercialization categories were identified: high, medium and low commercialization levels for each of cage, pond and tank aquaculture production systems. Second, an analytical farm household survey of 300 farmers was conducted in the counties of Kiambu (60), Kakamega (80), Siaya (80), Nyeri (45) and Kirinyaga (35) to analyse enabling factors in each of the nine commercialization categories. The enabling
    factors explored are income (in Kenyan Shillings [KES]), fingerling production [numbers], fish feed (floating pellets [tons]), transport (% of farmers who have their own transport), market outlets (% per outlet category), share of fish meals consumed per household (%), risk taking/aversion (perception ranking) and trust in government (perception ranking). Third, a qualitative literature survey was conducted to review best practice in commercialization of the aquaculture sector in Kenya. The analyses show that enabling factors differ substantially across the nine categories. The main motivations of pond farming are to ensure food and
    nutrition security; it is deemed successful when costs can be covered by generated income, even without further investments to commercialise. Pond farming is therefore the least commercialized segment of the aquaculture sector, although it has obtained the most subsidies in the past. Cage farming is expanding substantially in Lake Victoria, and regulations and planning to monitor environmental impacts are urgently needed. Given the high number of
    new investors, cage farming is expected to contribute significantly to aquaculture supply in the future. Tank farming is a highly commercialized segment that depends on appropriate technology, which is expensive and accessible only to a few fish farmers. However, the efficiency in use of water, feed and land; the reduced risks of losses; and the possibly low distance to urban markets can make this segment a critical supplier of fish to a large consumer group in the future. Overall, it is advised that future investors in aquaculture in Kenya should be aware of the specific enabling factors of each category and should target the most critical enabling factors.
    Biosensor never misses a tumour
    Beekman, Pepijn - \ 2020
    Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug–metabolite atlas
    Liu, Jun ; Lahousse, Lies ; Nivard, Michel G. ; Bot, Mariska ; Chen, Lianmin ; Klinken, Jan Bert van; Thesing, Carisha S. ; Beekman, Marian ; Akker, Erik Ben van den; Slieker, Roderick C. ; Waterham, Eveline ; Kallen, Carla J.H. van der; Boer, Irene de; Li-Gao, Ruifang ; Vojinovic, Dina ; Amin, Najaf ; Radjabzadeh, Djawad ; Kraaij, Robert ; Alferink, Louise J.M. ; Murad, Sarwa Darwish ; Uitterlinden, André G. ; Willemsen, Gonneke ; Pool, Rene ; Milaneschi, Yuri ; Heemst, Diana van; Suchiman, H.E. ; Rutters, Femke ; Elders, Petra J.M. ; Beulens, Joline W.J. ; Heijden, Amber A.W.A. van der; Greevenbroek, Marleen M.J. van; Arts, Ilja C.W. ; Onderwater, Gerrit L.J. ; Maagdenberg, Arn M.J.M. van den; Mook-Kanamori, Dennis O. ; Hankemeier, Thomas ; Terwindt, Gisela M. ; Stehouwer, Coen D.A. ; Geleijnse, Johanna M. ; ‘t Hart, Leen M. ; Slagboom, Eline P. ; Dijk, Ko Willems van; Zhernakova, Alexandra ; Fu, Jingyuan ; Penninx, Brenda W.J.H. ; Boomsma, Dorret I. ; Demirkan, Ayşe ; Stricker, Bruno H.C. ; Duijn, Cornelia M. van - \ 2020
    Nature Medicine 26 (2020)1. - ISSN 1078-8956 - p. 110 - 117.

    Progress in high-throughput metabolic profiling provides unprecedented opportunities to obtain insights into the effects of drugs on human metabolism. The Biobanking BioMolecular Research Infrastructure of the Netherlands has constructed an atlas of drug–metabolite associations for 87 commonly prescribed drugs and 150 clinically relevant plasma-based metabolites assessed by proton nuclear magnetic resonance. The atlas includes a meta-analysis of ten cohorts (18,873 persons) and uncovers 1,071 drug–metabolite associations after evaluation of confounders including co-treatment. We show that the effect estimates of statins on metabolites from the cross-sectional study are comparable to those from intervention and genetic observational studies. Further data integration links proton pump inhibitors to circulating metabolites, liver function, hepatic steatosis and the gut microbiome. Our atlas provides a tool for targeted experimental pharmaceutical research and clinical trials to improve drug efficacy, safety and repurposing. We provide a web-based resource for visualization of the atlas (http://bbmri.researchlumc.nl/atlas/).

    Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
    Hagenbeek, Fiona A. ; Pool, René ; Dongen, Jenny van; Draisma, Harmen H.M. ; Hottenga, Jouke Jan ; Willemsen, Gonneke ; Abdellaoui, Abdel ; Fedko, Iryna O. ; Braber, Anouk den; Visser, Pieter Jelle ; Geus, Eco J.C.N. de; Willems van Dijk, Ko ; Verhoeven, Aswin ; Suchiman, H.E. ; Beekman, Marian ; Slagboom, Eline P. ; Duijn, Cornelia M. van; Barkey Wolf, J.J.H. ; Cats, D. ; Amin, N. ; Beulens, J.W. ; Bom, J.A. van der; Bomer, N. ; Demirkan, A. ; Hilten, J.A. van; Meessen, J.M.T.A. ; Moed, M.H. ; Fu, J. ; Onderwater, G.L.J. ; Rutters, F. ; So-Osman, C. ; Flier, W.M. van der; Heijden, A.A.W.A. van der; Spek, A. van der; Asselbergs, F.W. ; Boersma, E. ; Elders, P.M. ; Geleijnse, J.M. ; Ikram, M.A. ; Kloppenburg, M. ; Meulenbelt, I. ; Mooijaart, S.P. ; Nelissen, R.G.H.H. ; Netea, M.G. ; Penninx, B.W.J.H. ; Stehouwer, C.D.A. ; Teunissen, C.E. ; Terwindt, G.M. ; Jukema, J.W. ; Reinders, M.J.T. - \ 2020
    Nature Communications 11 (2020)1. - ISSN 2041-1723

    Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2 Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.

    Electrochemical detection of tumor-derived extracellular vesicles on nanointerdigitated electrodes
    Mathew, Dilu G. ; Beekman, Pepijn ; Lemay, Serge G. ; Zuilhof, Han ; Gac, Séverine Le; Wiel, Wilfred G. van der - \ 2020
    Nano Letters 20 (2020)2. - ISSN 1530-6984 - p. 820 - 828.
    enzymatic amplification - microfluidics - Nanoelectrodes - redox cycling - tumor-derived extracellular vesicles

    Tumor-derived extracellular vesicles (tdEVs) are attracting much attention due to their essential function in intercellular communication and their potential as cancer biomarkers. Although tdEVs are significantly more abundant in blood than other cancer biomarkers, their concentration compared to other blood components remains relatively low. Moreover, the presence of particles in blood with a similar size as that of tdEVs makes their selective and sensitive detection further challenging. Therefore, highly sensitive and specific biosensors are required for unambiguous tdEV detection in complex biological environments, especially for decentralized point-of-care analysis. Here, we report an electrochemical sensing scheme for tdEV detection, with two-level selectivity provided by a sandwich immunoassay and two-level amplification through the combination of an enzymatic assay and redox cycling on nanointerdigitated electrodes to respectively enhance the specificity and sensitivity of the assay. Analysis of prostate cancer cell line tdEV samples at various concentrations revealed an estimated limit of detection for our assay as low as 5 tdEVs/μL, as well as an excellent linear sensor response spreading over 6 orders of magnitude (10-106 tdEVs/μL), which importantly covers the clinically relevant range for tdEV detection in blood. This novel nanosensor and associated sensing scheme opens new opportunities to detect tdEVs at clinically relevant concentrations from a single blood finger prick.

    A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals
    Deelen, Joris ; Kettunen, Johannes ; Fischer, Krista ; Spek, Ashley van der; Trompet, Stella ; Kastenmüller, Gabi ; Boyd, Andy ; Zierer, Jonas ; Akker, Erik B. van den; Ala-Korpela, Mika ; Amin, Najaf ; Demirkan, Ayse ; Ghanbari, Mohsen ; Heemst, Diana van; Ikram, Arfan ; Klinken, Jan Bert van; Mooijaart, Simon P. ; Peters, Annette ; Salomaa, Veikko ; Sattar, Naveed ; Spector, Tim D. ; Tiemeier, Henning ; Verhoeven, Aswin ; Waldenberger, Melanie ; Würtz, Peter ; Davey Smith, George ; Metspalu, Andres ; Perola, Markus ; Menni, Cristina ; Geleijnse, Johanna M. ; Drenos, Fotios ; Beekman, Marian ; Jukema, Wouter ; Duijn, Cornelia M. van; Slagboom, Eline - \ 2019
    Nature Communications 10 (2019). - ISSN 2041-1723

    Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of long-term mortality in the circulation of 44,168 individuals (age at baseline 18–109), of whom 5512 died during follow-up. We apply a stepwise (forward-backward) procedure based on meta-analysis results and identify 14 circulating biomarkers independently associating with all-cause mortality. Overall, these associations are similar in men and women and across different age strata. We subsequently show that the prediction accuracy of 5- and 10-year mortality based on a model containing the identified biomarkers and sex (C-statistic = 0.837 and 0.830, respectively) is better than that of a model containing conventional risk factors for mortality (C-statistic = 0.772 and 0.790, respectively). The use of the identified metabolic profile as a predictor of mortality or surrogate endpoint in clinical studies needs further investigation.

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