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31 results on '"de Bruijn, R"'

1. Biodiversity responses to Lateglacial climate change in the subdecadally-resolved record of Lake Hämelsee (Germany)

Author

Engels, S., Lane, C. S., Hoek, W. Z., Baneschi, I., Bouwman, A., Brogan, E., Bronk Ramsey, C., Collins, J., de Bruijn, R., Haliuc, A., Heiri, O., Hubay, K., Jones, G., Jones, V., Laug, A., Merkt, J., Muschitiello, F., Müller, M., Peters, T., Peterse, F., Pueschel, A., Staff, R. A., ter Schure, A., Turner, F., van den Bos, V., Wagner-Cremer, F., Engels, S., Lane, C. S., Hoek, W. Z., Baneschi, I., Bouwman, A., Brogan, E., Bronk Ramsey, C., Collins, J., de Bruijn, R., Haliuc, A., Heiri, O., Hubay, K., Jones, G., Jones, V., Laug, A., Merkt, J., Muschitiello, F., Müller, M., Peters, T., Peterse, F., Pueschel, A., Staff, R. A., ter Schure, A., Turner, F., van den Bos, V., and Wagner-Cremer, F.

Abstract

Anthropogenically-driven climate warming and land use change are the main causes of an ongoing decrease in global biodiversity. It is unclear how ecosystems, particularly freshwater habitats, will respond to such continuous and potentially intensifying disruptions. Here we analyse how different components of terrestrial and aquatic ecosystems responded to natural climate change during the Lateglacial. By applying a range of analytical techniques (sedimentology, palaeoecology, geochemistry) to the well-dated sediment archive from Lake Hämelsee (Germany), we show evidence for vegetation development, landscape dynamics and aquatic ecosystem change typical for northwest Europe during the Lateglacial. By particularly focussing on periods of abrupt climate change, we determine the timing and duration of changes in biodiversity in response to external forcing. We show that onsets of changes in biodiversity indicators (e.g. diatom composition, Pediastrum concentrations) lag changes in environmental records (e.g. loss-on-ignition) by a few decades, particularly at the Allerød/Younger Dryas transition. Most biodiversity indicators showed transition times of 10–50 years, whereas environmental records typically showed a 50–100 year long transition. In some cases, transition times observed for the compositional turnover or productivity records were up to 185 years, which could have been the result of the combined effects of direct (e.g. climate) and indirect (e.g. lake stratification) drivers of ecosystem change. Our results show differences in timing and duration of biodiversity responses to external disturbances, suggesting that a multi-decadal view needs to be taken when designing effective conservation management of freshwater ecosystems under current global warming.

Published
2024

2. Biodiversity responses to Lateglacial climate change in the subdecadally-resolved record of Lake Hämelsee (Germany)

Author

Geomorfologie, Coastal dynamics, Fluvial systems and Global change, Organic geochemistry, Dep Fysische Geografie, Palaeo-ecologie, Engels, S., Lane, C. S., Hoek, W. Z., Baneschi, I., Bouwman, A., Brogan, E., Bronk Ramsey, C., Collins, J., de Bruijn, R., Haliuc, A., Heiri, O., Hubay, K., Jones, G., Jones, V., Laug, A., Merkt, J., Muschitiello, F., Müller, M., Peters, T., Peterse, F., Pueschel, A., Staff, R. A., ter Schure, A., Turner, F., van den Bos, V., Wagner-Cremer, F., Geomorfologie, Coastal dynamics, Fluvial systems and Global change, Organic geochemistry, Dep Fysische Geografie, Palaeo-ecologie, Engels, S., Lane, C. S., Hoek, W. Z., Baneschi, I., Bouwman, A., Brogan, E., Bronk Ramsey, C., Collins, J., de Bruijn, R., Haliuc, A., Heiri, O., Hubay, K., Jones, G., Jones, V., Laug, A., Merkt, J., Muschitiello, F., Müller, M., Peters, T., Peterse, F., Pueschel, A., Staff, R. A., ter Schure, A., Turner, F., van den Bos, V., and Wagner-Cremer, F.

Published
2024

3. Daphnia magna's Favorite snack: Biofouled plastics

Author

Polhill, L., de Bruijn, R., Amaral-Zettler, L., Praetorius, A., van Wezel, A., Polhill, L., de Bruijn, R., Amaral-Zettler, L., Praetorius, A., and van Wezel, A.

Abstract

The influence of biofouling on zooplankton ingestion rates of plastics in freshwater environments has received limited attention. We investigated how biofouling of microplastics in wastewater effluent and in fresh surface water influences Daphnia magna's microplastic consumption. The differences in ingestion of the biofouled as compared with the virgin microplastics were higher for the surface water by a factor of seven compared with a factor of two for the effluent. The intake of biofouled microplastics by D. magna was higher compared with virgin plastics, but the reason for this preference should be further investigated. Environ Toxicol Chem 2022;00:1–6. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Published
2022

4. Daphnia magna's favorite snack: Biofouled plastics

Author

Polhill, L., de Bruijn, R., Amaral-Zettler, L., Praetorius, A., van Wezel, A., Polhill, L., de Bruijn, R., Amaral-Zettler, L., Praetorius, A., and van Wezel, A.

Abstract

The influence of biofouling on zooplankton ingestion rates of plastics in freshwater environments has received limited attention. We investigated how biofouling of microplastics in wastewater effluent and in fresh surface water influences Daphnia magna's microplastic consumption. The differences in ingestion of the biofouled as compared with the virgin microplastics were higher for the surface water by a factor of seven compared with a factor of two for the effluent. The intake of biofouled microplastics by D. magna was higher compared with virgin plastics, but the reason for this preference should be further investigated. Environ Toxicol Chem 2022;00:1–6. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Published
2022

5. Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer

Author

Ratz, L., Brambillasca, C., Bartke, L., Huetzen, M., Goergens, J., Leidecker, O., Jachimowicz, R., van de Ven, M., Proost, N., Siteur, B., de Korte-Grimmerink, R., Bouwman, P., Pulver, E. M., de Bruijn, R., Isensee, J., Hucho, T., Pandey, G., van Lohuizen, M., Mallmann, P., Reinhardt, H. C., Jonkers, J., Puppe, J., Ratz, L., Brambillasca, C., Bartke, L., Huetzen, M., Goergens, J., Leidecker, O., Jachimowicz, R., van de Ven, M., Proost, N., Siteur, B., de Korte-Grimmerink, R., Bouwman, P., Pulver, E. M., de Bruijn, R., Isensee, J., Hucho, T., Pandey, G., van Lohuizen, M., Mallmann, P., Reinhardt, H. C., Jonkers, J., and Puppe, J.

Published
2022

6. Comparative oncogenomics identifies combinations of driver genes and drug targets in BRCA1-mutated breast cancer

Author

Annunziato, S, de Ruiter, JR, Henneman, L, Brambillasca, CS, Lutz, C, Vaillant, F, Ferrante, F, Drenth, AP, van der Burg, E, Siteur, B, van Gerwen, B, de Bruijn, R, van Miltenburg, MH, Huijbers, IJ, van de Ven, M, Visvader, JE, Lindeman, GJ, Wessels, LFA, Jonkers, J, Annunziato, S, de Ruiter, JR, Henneman, L, Brambillasca, CS, Lutz, C, Vaillant, F, Ferrante, F, Drenth, AP, van der Burg, E, Siteur, B, van Gerwen, B, de Bruijn, R, van Miltenburg, MH, Huijbers, IJ, van de Ven, M, Visvader, JE, Lindeman, GJ, Wessels, LFA, and Jonkers, J

Abstract

BRCA1-mutated breast cancer is primarily driven by DNA copy-number alterations (CNAs) containing large numbers of candidate driver genes. Validation of these candidates requires novel approaches for high-throughput in vivo perturbation of gene function. Here we develop genetically engineered mouse models (GEMMs) of BRCA1-deficient breast cancer that permit rapid introduction of putative drivers by either retargeting of GEMM-derived embryonic stem cells, lentivirus-mediated somatic overexpression or in situ CRISPR/Cas9-mediated gene disruption. We use these approaches to validate Myc, Met, Pten and Rb1 as bona fide drivers in BRCA1-associated mammary tumorigenesis. Iterative mouse modeling and comparative oncogenomics analysis show that MYC-overexpression strongly reshapes the CNA landscape of BRCA1-deficient mammary tumors and identify MCL1 as a collaborating driver in these tumors. Moreover, MCL1 inhibition potentiates the in vivo efficacy of PARP inhibition (PARPi), underscoring the therapeutic potential of this combination for treatment of BRCA1-mutated cancer patients with poor response to PARPi monotherapy.

Published
2019

7. The Lateglacial to early Holocene tephrochronological record from Lake Hämelsee, Germany: a key site within the European tephra framework

Author

Jones, G., Lane, C.S., Brauer, A., Davies, S.M., de Bruijn, R., Engels, S., Haliuc, A., Hoek, W.Z., Merkt, J., Sachse, D., Turner, F., Wagner, F., Jones, G., Lane, C.S., Brauer, A., Davies, S.M., de Bruijn, R., Engels, S., Haliuc, A., Hoek, W.Z., Merkt, J., Sachse, D., Turner, F., and Wagner, F.

Abstract

Here we present the results of a detailed cryptotephra investigation through the Lateglacial to early Holocene transition, from a new sediment core record obtained from Lake Hämelsee, Germany. Two tephra horizons, the Laacher See Tephra (Eifel Volcanic Field) and the Saksunarvatn Ash (Iceland), have been previously described in this partially varved sediment record, indicating the potential of the location as an important Lateglacial tephrochronological site in northwest Europe. We have identified three further tephra horizons, which we correlate to: the c. 12.1 ka BP Vedde Ash (Iceland), the c. 11 ka BP Ulmener Maar tephra (Eifel Volcanic Field) and the c. 10.8 ka BP Askja-S tephra (Iceland). Three additional cryptotephra deposits have been found (locally named HÄM_T1616, HÄM_T1470 and HÄM_T1456-1455), which cannot be correlated to any known eruption at present. Geochemical analysis of the deposits suggests that these cryptotephras most likely have an Icelandic origin. Our discoveries provide age constraints for the new sediment records from Lake Hämelsee and enable direct stratigraphical correlations to be made with other tephra-bearing sites across Europe. The new tephrostratigraphical record, within a partially varved Lateglacial sediment record, highlights the importance of Lake Hämelsee as a key site within the European tephra lattice.

Published
2018

8. The Lateglacial to early Holocene tephrochronological record from Lake Hämelsee, Germany: a key site within the European tephra framework

Author

Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Palaeo-ecologie, Jones, G., Lane, C.S., Brauer, A., Davies, S.M., de Bruijn, R., Engels, S., Haliuc, A., Hoek, W.Z., Merkt, J., Sachse, D., Turner, F., Wagner, F., Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Palaeo-ecologie, Jones, G., Lane, C.S., Brauer, A., Davies, S.M., de Bruijn, R., Engels, S., Haliuc, A., Hoek, W.Z., Merkt, J., Sachse, D., Turner, F., and Wagner, F.

Published
2018

9. The Lateglacial to early Holocene tephrochronological record from Lake Hämelsee, Germany: a key site within the European tephra framework

Author

Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Palaeo-ecologie, Jones, G., Lane, C.S., Brauer, A., Davies, S.M., de Bruijn, R., Engels, S., Haliuc, A., Hoek, W.Z., Merkt, J., Sachse, D., Turner, F., Wagner, F., Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Palaeo-ecologie, Jones, G., Lane, C.S., Brauer, A., Davies, S.M., de Bruijn, R., Engels, S., Haliuc, A., Hoek, W.Z., Merkt, J., Sachse, D., Turner, F., and Wagner, F.

Published
2018

10. The Lateglacial to early Holocene tephrochronological record from Lake Hämelsee, Germany: a key site within the European tephra framework

Author

Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Palaeo-ecologie, Jones, G., Lane, C.S., Brauer, A., Davies, S.M., de Bruijn, R., Engels, S., Haliuc, A., Hoek, W.Z., Merkt, J., Sachse, D., Turner, F., Wagner, F., Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Palaeo-ecologie, Jones, G., Lane, C.S., Brauer, A., Davies, S.M., de Bruijn, R., Engels, S., Haliuc, A., Hoek, W.Z., Merkt, J., Sachse, D., Turner, F., and Wagner, F.

Published
2018

11. Mapping buried Holocene landscapes: past lowland environments, palaeoDEMs and preservation in GIS

Author

Cohen, K.M., Dambrink, R., de Bruijn, R., Marges, V.C., Erkens, G., Pierik, H.J., Koster, K., Stafleu, J, Schokker, J., Hijma, M.P., Cohen, K.M., Dambrink, R., de Bruijn, R., Marges, V.C., Erkens, G., Pierik, H.J., Koster, K., Stafleu, J, Schokker, J., and Hijma, M.P.

Abstract

In a geological GIS-data recombination project, a digital map was produced that holds information on the Netherlands’ former coastal and delta plain landscapes in the last 14,000 years: the Holocene and the very end of the Pleistocene. The end product polygon maps are accompanied by a set of palaeoDEMs indicating the ‘attention depth’ for buried land surfaces and aquatic deposits; both for four time slices. This paper provides conceptual background on legend and construction principles of the polygon maps and the palaeoDEMs (‘decisions during the making off’) and a basic overview of the map product (‘landscape structure’, ‘burial depth’, ‘preser¬vation’), visualised for the four time slices of RCE’s Archaeological Knowledge Kit. The text links the coastal plain buried landscape mapping for time slices T0, T1, T2 and T3, to the other Knowledge Kit activities described in this volume, notably that of the Archaeological Landscape map (for time slice T4 in the coastal plain part of The Netherlands, for time slice T0 to T4 in the Pleistocene uplands).

Published
2017

12. Vervaardiging van begraven landschapskaarten voor Holoceen afgedekt Nederland: Kaartlaag T0123 voor RCE’s Kenniskaart-portaal

Author

Cohen, K.M., de Bruijn, R., Marges, V.C., de Vries, S., Pierik, H.J., Vos, P.C., Erkens, G., Hijma, M.P., Cohen, K.M., de Bruijn, R., Marges, V.C., de Vries, S., Pierik, H.J., Vos, P.C., Erkens, G., and Hijma, M.P.

Abstract

Ten behoeve van gebruik in een door de opdrachtgever (RCE) op te zetten digitaal portaal met informatie voor archeologische professionals, is een landsdekkend kaartbestand (T0123.shp) met begraven landschappen uit de laatste 14,000 jaar gemaakt. Daartoe is een methodiek ontwikkeld voor het op geautomatiseerde en reproduceerbare wijze vervaardigen van deze kaart. Het kaartbestand sluit aan op RCE’s Archeologische Landschappenkaart 2.1. De kartering bestrijkt vier archeologisch relevante tijdsneden, en verwerkt daartoe bestaande digitale geologische kaartbestanden, zoals die door de betrokken partijen (TNO, UU, Deltares) worden onderhouden. In een serie selectie- en combinatiebewerkingen, zijn uit die kaartlagen, nieuwe kaartbeelden per tijdsnede gegenereerd, met op landelijk archeologisch gebruik gerichte opbouw en indeling (legenda). De kaarten zijn door Deltares, de Universiteit Utrecht en TNO Geologische Dienst Nederland volgens een geïntegreerd Plan van Aanpak geproduceerd. Een en ander vond plaats in het kader van project ‘Verwachtingen in Lagen’ binnen het programma ‘Kenniskaart’ van de Rijksdienst voor het Cultureel Erfgoed (Opdracht RCE-10B). Dit deelrapport beschrijft de totstandkoming van het digitale kaartproduct ‘T0123.shp’ en voorbereidende stappen van synchronisatie van de te verwerken basisbestanden. In een tweede rapport, zijn de in de kartering gebruikte gebiedsindeling en landschapszonering beschreven (Deltares rapport 1210450-000-BGS-0014). Een derde deelrapport betreft de parallelle vervaardiging van paleo-hoogtemodellen (TNO rapport 2015-R10685). Een opleggerrapport documenteert het totale project (Deltares rapport 1210450-000-BGS-0012). De doelgroep van dit deelrapport is de GIS-vaardige professional. Het opleggerrapport en het indelingsbeschrijvende deelrapport hebben een bredere groep professionals die zich met landschapsarcheologie, fysische geografie en Holocene geologie van Nederland bezig houden als doel

Published
2017

13. Vervaardiging van hoogtemodellen en landschapskaarten naar periode en diepte voor archeologisch gebruik in Holoceen-afgedekte delen van Nederland

Author

Cohen, K.M., Dambrink, R., de Bruijn, R., Schokker, J., Hijma, M.P., Cohen, K.M., Dambrink, R., de Bruijn, R., Schokker, J., and Hijma, M.P.

Abstract

Ten behoeve van gebruik in een later door de opdrachtgever, de Rijksdienst voor Cultureel Erfgoed (RCE), op te zetten digitaal portaal met informatie voor archeologische professionals, zijn een landsdekkend kaartbestand (T0123.shp) met begraven landschappen uit de laatste 14.000 jaar en een bijbehorende serie paleohoogtemodellen gemaakt. Naast deze digitale bestanden is ook de geautomatiseerde wijze van productie (een serie scripts) onderdeel van het voltooide product. De kartering bestrijkt vier archeologisch relevante tijdsneden en verwerkt daartoe bestaande digitale geologische kaartbestanden zoals die door de betrokken partijen, TNO - Geologische Dienst van Nederland (TNO-GDN), de Universiteit Utrecht (UU) en Deltares, worden onderhouden. Uitgaande van die dataproducten zijn in een serie selectie- en combinatiebewerkingen nieuwe kaartbeelden per tijdsnede gegenereerd, met een op landelijk archeologisch gebruik gerichte opbouw en indeling (legenda). De kaarten en paleohoogtemodellen zijn door Deltares, TNO-GDN en de UU volgens een geïntegreerd Plan van Aanpak geproduceerd, in het kader van project ‘Verwachtingen in Lagen’ binnen het programma ‘Kenniskaart’ van de RCE. Geheel nieuw is daarbij dat de methodiek van productie zodanig is opgezet, dat het geleverde in de toekomst eenvoudig reproduceerbaar en te actualiseren is. Er zijn geen nieuwe primaire gegevens verzameld. Er hebben wel voorbereidende en afstemmende bewerkingen op de verschillende te combineren dataproducten plaatsgevonden. Dit opleggerrapport beschrijft de standaardopmaak van digitale kaartlaag ‘T0123’ in aansluiting op de door RCE voor het huidige oppervlak ontwikkelde Archeologische Landschappenkaart. In het projectgebed dekt die laatste kaart tijdsnede ‘T4’: 900 na Chr. tot heden. Het opleggerrapport beschrijft ook de samenhang met de hoogtemodellen (‘attentiediepte’) voor landschappen uit prehistorische perioden T0, T1, T2 en T3 (van 12.000 voor Chr. tot 900 na Chr.). Samenvat

Published
2017

14. Vervaardiging van begraven landschapskaarten voor Holoceen afgedekt Nederland: Kaartlaag T0123 voor RCE’s Kenniskaart-portaal

Author

Geomorfologie, Coastal dynamics, Fluvial systems and Global change, Cohen, K.M., de Bruijn, R., Marges, V.C., de Vries, S., Pierik, H.J., Vos, P.C., Erkens, G., Hijma, M.P., Geomorfologie, Coastal dynamics, Fluvial systems and Global change, Cohen, K.M., de Bruijn, R., Marges, V.C., de Vries, S., Pierik, H.J., Vos, P.C., Erkens, G., and Hijma, M.P.

Published
2017

16. Mapping buried Holocene landscapes: past lowland environments, palaeoDEMs and preservation in GIS

Author

Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Cohen, K.M., Dambrink, R., de Bruijn, R., Marges, V.C., Erkens, G., Pierik, H.J., Koster, K., Stafleu, J, Schokker, J., Hijma, M.P., Lauwerier, R.C.G.M., Eerden, M.C., Groenewoudt, B.J., Lascaris, M.A., Rensink, E., Smit, B.I., Speleers, B.P., van Doesburg, J., Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Cohen, K.M., Dambrink, R., de Bruijn, R., Marges, V.C., Erkens, G., Pierik, H.J., Koster, K., Stafleu, J, Schokker, J., Hijma, M.P., Lauwerier, R.C.G.M., Eerden, M.C., Groenewoudt, B.J., Lascaris, M.A., Rensink, E., Smit, B.I., Speleers, B.P., and van Doesburg, J.

Published
2017

17. Vervaardiging van begraven landschapskaarten voor Holoceen afgedekt Nederland: Kaartlaag T0123 voor RCE’s Kenniskaart-portaal

Author

Geomorfologie, Coastal dynamics, Fluvial systems and Global change, Cohen, K.M., de Bruijn, R., Marges, V.C., de Vries, S., Pierik, H.J., Vos, P.C., Erkens, G., Hijma, M.P., Geomorfologie, Coastal dynamics, Fluvial systems and Global change, Cohen, K.M., de Bruijn, R., Marges, V.C., de Vries, S., Pierik, H.J., Vos, P.C., Erkens, G., and Hijma, M.P.

Published
2017

19. Mapping buried Holocene landscapes: past lowland environments, palaeoDEMs and preservation in GIS

Author

Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Cohen, K.M., Dambrink, R., de Bruijn, R., Marges, V.C., Erkens, G., Pierik, H.J., Koster, K., Stafleu, J, Schokker, J., Hijma, M.P., Lauwerier, R.C.G.M., Eerden, M.C., Groenewoudt, B.J., Lascaris, M.A., Rensink, E., Smit, B.I., Speleers, B.P., van Doesburg, J., Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Cohen, K.M., Dambrink, R., de Bruijn, R., Marges, V.C., Erkens, G., Pierik, H.J., Koster, K., Stafleu, J, Schokker, J., Hijma, M.P., Lauwerier, R.C.G.M., Eerden, M.C., Groenewoudt, B.J., Lascaris, M.A., Rensink, E., Smit, B.I., Speleers, B.P., and van Doesburg, J.

Published
2017

20. Vervaardiging van begraven landschapskaarten voor Holoceen afgedekt Nederland: Kaartlaag T0123 voor RCE’s Kenniskaart-portaal

Author

Geomorfologie, Coastal dynamics, Fluvial systems and Global change, Cohen, K.M., de Bruijn, R., Marges, V.C., de Vries, S., Pierik, H.J., Vos, P.C., Erkens, G., Hijma, M.P., Geomorfologie, Coastal dynamics, Fluvial systems and Global change, Cohen, K.M., de Bruijn, R., Marges, V.C., de Vries, S., Pierik, H.J., Vos, P.C., Erkens, G., and Hijma, M.P.

Published
2017

22. Mapping buried Holocene landscapes: past lowland environments, palaeoDEMs and preservation in GIS

Author

Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Lauwerier, R.C.G.M., Eerden, M.C., Groenewoudt, B.J., Lascaris, M.A., Rensink, E., Smit, B.I., Speleers, B.P., van Doesburg, J., Cohen, K.M., Dambrink, R., de Bruijn, R., Marges, V.C., Erkens, G., Pierik, H.J., Koster, K., Stafleu, J, Schokker, J., Hijma, M.P., Coastal dynamics, Fluvial systems and Global change, Geomorfologie, Lauwerier, R.C.G.M., Eerden, M.C., Groenewoudt, B.J., Lascaris, M.A., Rensink, E., Smit, B.I., Speleers, B.P., van Doesburg, J., Cohen, K.M., Dambrink, R., de Bruijn, R., Marges, V.C., Erkens, G., Pierik, H.J., Koster, K., Stafleu, J, Schokker, J., and Hijma, M.P.

Published
2017

23. Age- And sex-specific causal effects of adiposity on cardiovascular risk factors

Author

Fall, T, Hägg, S, Ploner, A, Mägi, R, Fischer, K, Draisma, H, Sarin, A, Benyamin, B, Ladenvall, C, Åkerlund, M, Kals, M, Esko, T, Nelson, C, Kaakinen, M, Huikari, V, Mangino, M, Meirhaeghe, A, Kristiansson, K, Nuotio, M, Kobl, M, Grallert, H, Dehghan, A, Kuningas, M, de Vries, P, de Bruijn, R, Willems, S, Heikkilä, K, Silventoinen, K, Pietiläinen, K, Legry, V, Giedraitis, V, Goumidi, L, Syvänen, A, Strauch, K, Koenig, W, Lichtner, P, Herder, C, Palotie, A, Menni, C, Uitterlinden, A, Kuulasmaa, K, Havulinna, A, Moreno, L, Gonzalez Gross, M, Evans, A, Tregouet, D, Yarnell, J, Virtamo, J, Ferrières, J, Veronesi, G, Perola, M, Arveiler, D, Brambilla, P, Lind, L, Kaprio, J, Hofman, A, Stricker, B, van Duijn, C, Ikram, M, Franco, O, Cottel, D, Dallongeville, J, Hall, A, Jula, A, Tobin, M, Penninx, B, Peters, A, Gieger, C, Samani, N, Montgomery, G, Whitfield, J, Martin, N, Groop, L, Spector, T, Magnusson, P, Amouyel, P, Boomsma, D, Nilsson, P, Järvelin, M, Lyssenko, V, Metspalu, A, Strachan, D, Salomaa, V, Ripatti, S, Pedersen, N, Prokopenko, I, Mccarthy, M, Ingelsson, E, BRAMBILLA, PAOLO, Ingelsson, E., Fall, T, Hägg, S, Ploner, A, Mägi, R, Fischer, K, Draisma, H, Sarin, A, Benyamin, B, Ladenvall, C, Åkerlund, M, Kals, M, Esko, T, Nelson, C, Kaakinen, M, Huikari, V, Mangino, M, Meirhaeghe, A, Kristiansson, K, Nuotio, M, Kobl, M, Grallert, H, Dehghan, A, Kuningas, M, de Vries, P, de Bruijn, R, Willems, S, Heikkilä, K, Silventoinen, K, Pietiläinen, K, Legry, V, Giedraitis, V, Goumidi, L, Syvänen, A, Strauch, K, Koenig, W, Lichtner, P, Herder, C, Palotie, A, Menni, C, Uitterlinden, A, Kuulasmaa, K, Havulinna, A, Moreno, L, Gonzalez Gross, M, Evans, A, Tregouet, D, Yarnell, J, Virtamo, J, Ferrières, J, Veronesi, G, Perola, M, Arveiler, D, Brambilla, P, Lind, L, Kaprio, J, Hofman, A, Stricker, B, van Duijn, C, Ikram, M, Franco, O, Cottel, D, Dallongeville, J, Hall, A, Jula, A, Tobin, M, Penninx, B, Peters, A, Gieger, C, Samani, N, Montgomery, G, Whitfield, J, Martin, N, Groop, L, Spector, T, Magnusson, P, Amouyel, P, Boomsma, D, Nilsson, P, Järvelin, M, Lyssenko, V, Metspalu, A, Strachan, D, Salomaa, V, Ripatti, S, Pedersen, N, Prokopenko, I, Mccarthy, M, Ingelsson, E, BRAMBILLA, PAOLO, and Ingelsson, E.

Abstract

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 10-107) and stratified analyses (all P < 3.3 10-30). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ‡55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- And age-specific causal estimates on cardiovascular risk factors.

Published
2015

24. The role of adiposity in cardiometabolic traits: a mendelian randomization analysis

Author

Fall, T, Hägg, S, Mägi, R, Ploner, A, Fischer, K, Horikoshi, M, Sarin, A, Thorleifsson, G, Ladenvall, C, Kals, M, Kuningas, M, Draisma, H, Ried, J, Van, Z, Nr, Huikari, V, Mangino, M, Sonestedt, E, Benyamin, B, Nelson, C, Rivera, N, Kristiansson, K, Shen, H, Havulinna, A, Dehghan, A, Donnelly, L, Kaakinen, M, Nuotio, M, Robertson, N, de Bruijn, R, Ikram, M, Amin, N, Balmforth, A, Braund, P, Doney, A, Döring, A, Elliott, P, Esko, T, Franco, O, Gretarsdottir, S, Hartikainen, A, Heikkilä, K, Herzig, K, Holm, H, Hottenga, J, Hyppönen, E, Illig, T, Isaacs, A, Isomaa, B, Karssen, L, Kettunen, J, Koenig, W, Kuulasmaa, K, Laatikainen, T, Laitinen, J, Lindgren, C, Lyssenko, V, Läärä, E, Rayner, N, Männistö, S, Pouta, A, Rathmann, W, Rivadeneira, F, Ruokonen, A, Savolainen, M, Sijbrands, E, Small, K, Smit, J, Steinthorsdottir, V, Syvänen, A, Taanila, A, Tobin, M, Uitterlinden, A, Willems, S, Willemsen, G, Witteman, J, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Ferrario, M, Brambilla, P, Hall, A, Heath, A, Madden, P, Martin, N, Montgomery, G, Whitfield, J, Jula, A, Knekt, P, Oostra, B, van Duijn, C, Penninx, B, Davey Smith, G, Kaprio, J, Samani, N, Gieger, C, Peters, A, Wichmann, H, Boomsma, D, de Geus, E, Tuomi, T, Power, C, Hammond, C, Spector, T, Lind, L, Orho Melander, M, Palmer, C, Morris, A, Groop, L, Järvelin, M, Salomaa, V, Vartiainen, E, Hofman, A, Ripatti, S, Metspalu, A, Thorsteinsdottir, U, Stefansson, K, Pedersen, N, Mccarthy, M, Ingelsson, E, Prokopenko, I, Sarin, AP, Draisma, HH, Ried, JS, van, Zuydam, NR, Nelson, CP, Rivera, NV, Shen, HY, Havulinna, AS, Donnelly, LA, Nuotio, ML, de Bruijn, RF, Ikram, MA, Balmforth, AJ, Braund, PS, Doney, AS, Franco, OH, Hartikainen, AL, Herzig, KH, Hottenga, JJ, Karssen, LC, Rayner, NW, Savolainen, MJ, Sijbrands, EJ, Small, KS, Smit, JH, Syvänen, AC, Tobin, MD, Uitterlinden, AG, Willems, SM, Tregouet, DA, Ferrario, MM, BRAMBILLA, PAOLO, Hall, AS, Heath, AC, Madden, PA, Martin, NG, Montgomery, GW, Whitfield, JB, van Duijn, CM, Penninx, BW, Samani, NJ, Wichmann, HE, Boomsma, DI, de Geus, EJ, Hammond, CJ, Spector, TD, Palmer, CN, Morris, AD, Järvelin, MR, Pedersen, NL, McCarthy, MI, Prokopenko, I., Fall, T, Hägg, S, Mägi, R, Ploner, A, Fischer, K, Horikoshi, M, Sarin, A, Thorleifsson, G, Ladenvall, C, Kals, M, Kuningas, M, Draisma, H, Ried, J, Van, Z, Nr, Huikari, V, Mangino, M, Sonestedt, E, Benyamin, B, Nelson, C, Rivera, N, Kristiansson, K, Shen, H, Havulinna, A, Dehghan, A, Donnelly, L, Kaakinen, M, Nuotio, M, Robertson, N, de Bruijn, R, Ikram, M, Amin, N, Balmforth, A, Braund, P, Doney, A, Döring, A, Elliott, P, Esko, T, Franco, O, Gretarsdottir, S, Hartikainen, A, Heikkilä, K, Herzig, K, Holm, H, Hottenga, J, Hyppönen, E, Illig, T, Isaacs, A, Isomaa, B, Karssen, L, Kettunen, J, Koenig, W, Kuulasmaa, K, Laatikainen, T, Laitinen, J, Lindgren, C, Lyssenko, V, Läärä, E, Rayner, N, Männistö, S, Pouta, A, Rathmann, W, Rivadeneira, F, Ruokonen, A, Savolainen, M, Sijbrands, E, Small, K, Smit, J, Steinthorsdottir, V, Syvänen, A, Taanila, A, Tobin, M, Uitterlinden, A, Willems, S, Willemsen, G, Witteman, J, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Ferrario, M, Brambilla, P, Hall, A, Heath, A, Madden, P, Martin, N, Montgomery, G, Whitfield, J, Jula, A, Knekt, P, Oostra, B, van Duijn, C, Penninx, B, Davey Smith, G, Kaprio, J, Samani, N, Gieger, C, Peters, A, Wichmann, H, Boomsma, D, de Geus, E, Tuomi, T, Power, C, Hammond, C, Spector, T, Lind, L, Orho Melander, M, Palmer, C, Morris, A, Groop, L, Järvelin, M, Salomaa, V, Vartiainen, E, Hofman, A, Ripatti, S, Metspalu, A, Thorsteinsdottir, U, Stefansson, K, Pedersen, N, Mccarthy, M, Ingelsson, E, Prokopenko, I, Sarin, AP, Draisma, HH, Ried, JS, van, Zuydam, NR, Nelson, CP, Rivera, NV, Shen, HY, Havulinna, AS, Donnelly, LA, Nuotio, ML, de Bruijn, RF, Ikram, MA, Balmforth, AJ, Braund, PS, Doney, AS, Franco, OH, Hartikainen, AL, Herzig, KH, Hottenga, JJ, Karssen, LC, Rayner, NW, Savolainen, MJ, Sijbrands, EJ, Small, KS, Smit, JH, Syvänen, AC, Tobin, MD, Uitterlinden, AG, Willems, SM, Tregouet, DA, Ferrario, MM, BRAMBILLA, PAOLO, Hall, AS, Heath, AC, Madden, PA, Martin, NG, Montgomery, GW, Whitfield, JB, van Duijn, CM, Penninx, BW, Samani, NJ, Wichmann, HE, Boomsma, DI, de Geus, EJ, Hammond, CJ, Spector, TD, Palmer, CN, Morris, AD, Järvelin, MR, Pedersen, NL, McCarthy, MI, and Prokopenko, I.

Abstract

Background:The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.Methods and Findings:We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses.Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (

Published
2013

25. The role of adiposity in cardiometabolic traits: a mendelian randomization analysis

Author

Fall, T, Hägg, S, Mägi, R, Ploner, A, Fischer, K, Horikoshi, M, Sarin, A, Thorleifsson, G, Ladenvall, C, Kals, M, Kuningas, M, Draisma, H, Ried, J, Van, Z, Nr, Huikari, V, Mangino, M, Sonestedt, E, Benyamin, B, Nelson, C, Rivera, N, Kristiansson, K, Shen, H, Havulinna, A, Dehghan, A, Donnelly, L, Kaakinen, M, Nuotio, M, Robertson, N, de Bruijn, R, Ikram, M, Amin, N, Balmforth, A, Braund, P, Doney, A, Döring, A, Elliott, P, Esko, T, Franco, O, Gretarsdottir, S, Hartikainen, A, Heikkilä, K, Herzig, K, Holm, H, Hottenga, J, Hyppönen, E, Illig, T, Isaacs, A, Isomaa, B, Karssen, L, Kettunen, J, Koenig, W, Kuulasmaa, K, Laatikainen, T, Laitinen, J, Lindgren, C, Lyssenko, V, Läärä, E, Rayner, N, Männistö, S, Pouta, A, Rathmann, W, Rivadeneira, F, Ruokonen, A, Savolainen, M, Sijbrands, E, Small, K, Smit, J, Steinthorsdottir, V, Syvänen, A, Taanila, A, Tobin, M, Uitterlinden, A, Willems, S, Willemsen, G, Witteman, J, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Ferrario, M, Brambilla, P, Hall, A, Heath, A, Madden, P, Martin, N, Montgomery, G, Whitfield, J, Jula, A, Knekt, P, Oostra, B, van Duijn, C, Penninx, B, Davey Smith, G, Kaprio, J, Samani, N, Gieger, C, Peters, A, Wichmann, H, Boomsma, D, de Geus, E, Tuomi, T, Power, C, Hammond, C, Spector, T, Lind, L, Orho Melander, M, Palmer, C, Morris, A, Groop, L, Järvelin, M, Salomaa, V, Vartiainen, E, Hofman, A, Ripatti, S, Metspalu, A, Thorsteinsdottir, U, Stefansson, K, Pedersen, N, Mccarthy, M, Ingelsson, E, Prokopenko, I, Sarin, AP, Draisma, HH, Ried, JS, van, Zuydam, NR, Nelson, CP, Rivera, NV, Shen, HY, Havulinna, AS, Donnelly, LA, Nuotio, ML, de Bruijn, RF, Ikram, MA, Balmforth, AJ, Braund, PS, Doney, AS, Franco, OH, Hartikainen, AL, Herzig, KH, Hottenga, JJ, Karssen, LC, Rayner, NW, Savolainen, MJ, Sijbrands, EJ, Small, KS, Smit, JH, Syvänen, AC, Tobin, MD, Uitterlinden, AG, Willems, SM, Tregouet, DA, Ferrario, MM, BRAMBILLA, PAOLO, Hall, AS, Heath, AC, Madden, PA, Martin, NG, Montgomery, GW, Whitfield, JB, van Duijn, CM, Penninx, BW, Samani, NJ, Wichmann, HE, Boomsma, DI, de Geus, EJ, Hammond, CJ, Spector, TD, Palmer, CN, Morris, AD, Järvelin, MR, Pedersen, NL, McCarthy, MI, Prokopenko, I., Fall, T, Hägg, S, Mägi, R, Ploner, A, Fischer, K, Horikoshi, M, Sarin, A, Thorleifsson, G, Ladenvall, C, Kals, M, Kuningas, M, Draisma, H, Ried, J, Van, Z, Nr, Huikari, V, Mangino, M, Sonestedt, E, Benyamin, B, Nelson, C, Rivera, N, Kristiansson, K, Shen, H, Havulinna, A, Dehghan, A, Donnelly, L, Kaakinen, M, Nuotio, M, Robertson, N, de Bruijn, R, Ikram, M, Amin, N, Balmforth, A, Braund, P, Doney, A, Döring, A, Elliott, P, Esko, T, Franco, O, Gretarsdottir, S, Hartikainen, A, Heikkilä, K, Herzig, K, Holm, H, Hottenga, J, Hyppönen, E, Illig, T, Isaacs, A, Isomaa, B, Karssen, L, Kettunen, J, Koenig, W, Kuulasmaa, K, Laatikainen, T, Laitinen, J, Lindgren, C, Lyssenko, V, Läärä, E, Rayner, N, Männistö, S, Pouta, A, Rathmann, W, Rivadeneira, F, Ruokonen, A, Savolainen, M, Sijbrands, E, Small, K, Smit, J, Steinthorsdottir, V, Syvänen, A, Taanila, A, Tobin, M, Uitterlinden, A, Willems, S, Willemsen, G, Witteman, J, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Ferrario, M, Brambilla, P, Hall, A, Heath, A, Madden, P, Martin, N, Montgomery, G, Whitfield, J, Jula, A, Knekt, P, Oostra, B, van Duijn, C, Penninx, B, Davey Smith, G, Kaprio, J, Samani, N, Gieger, C, Peters, A, Wichmann, H, Boomsma, D, de Geus, E, Tuomi, T, Power, C, Hammond, C, Spector, T, Lind, L, Orho Melander, M, Palmer, C, Morris, A, Groop, L, Järvelin, M, Salomaa, V, Vartiainen, E, Hofman, A, Ripatti, S, Metspalu, A, Thorsteinsdottir, U, Stefansson, K, Pedersen, N, Mccarthy, M, Ingelsson, E, Prokopenko, I, Sarin, AP, Draisma, HH, Ried, JS, van, Zuydam, NR, Nelson, CP, Rivera, NV, Shen, HY, Havulinna, AS, Donnelly, LA, Nuotio, ML, de Bruijn, RF, Ikram, MA, Balmforth, AJ, Braund, PS, Doney, AS, Franco, OH, Hartikainen, AL, Herzig, KH, Hottenga, JJ, Karssen, LC, Rayner, NW, Savolainen, MJ, Sijbrands, EJ, Small, KS, Smit, JH, Syvänen, AC, Tobin, MD, Uitterlinden, AG, Willems, SM, Tregouet, DA, Ferrario, MM, BRAMBILLA, PAOLO, Hall, AS, Heath, AC, Madden, PA, Martin, NG, Montgomery, GW, Whitfield, JB, van Duijn, CM, Penninx, BW, Samani, NJ, Wichmann, HE, Boomsma, DI, de Geus, EJ, Hammond, CJ, Spector, TD, Palmer, CN, Morris, AD, Järvelin, MR, Pedersen, NL, McCarthy, MI, and Prokopenko, I.

Abstract

Background:The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.Methods and Findings:We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses.Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (

Published
2013

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