323 results on '"Slagboom, Eline"'
Search Results
2. Identified senescence endotypes in aged cartilage are reflected in the blood metabolome
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Boone, Ilja, Tuerlings, Margo, Coutinho de Almeida, Rodrigo, Lehmann, Johannes, Ramos, Yolande, Nelissen, Rob, Slagboom, Eline, de Keizer, Peter, and Meulenbelt, Ingrid
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- 2024
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3. Epigenome-wide association study of dietary fatty acid intake
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Lange de Luna, Julia, Nounu, Aayah, Neumeyer, Sonja, Sinke, Lucy, Wilson, Rory, Hellbach, Fabian, Matías-García, Pamela R., Delerue, Thomas, Winkelmann, Juliane, Peters, Annette, Thorand, Barbara, Beekman, Marian, Heijmans, Bastiaan T., Slagboom, Eline, Gieger, Christian, Linseisen, Jakob, and Waldenberger, Melanie
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- 2024
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4. Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways
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Kasher, Melody, Williams, Frances MK, Freidin, Maxim B, Malkin, Ida, Cherny, Stacey S, Benjamin, Emelia, Chasman, Daniel I, Dehghan, Abbas, Ahluwalia, Tarunveer Singh, Meigs, James, Tracy, Russell, Alizadeh, Behrooz Z, Ligthart, Symen, Bis, Josh, Eiriksdottir, Gudny, Pankratz, Nathan, Gross, Myron, Rainer, Alex, Snieder, Harold, Wilson, James G, Psaty, Bruce M, Dupuis, Josee, Prins, Bram, Vaso, Urmo, Stathopoulou, Maria, Franke, Lude, Lehtimaki, Terho, Koenig, Wolfgang, Jamshidi, Yalda, Siest, Sophie, Abbasi, Ali, Uitterlinden, Andre G, Abdollahi, Mohammadreza, Schnabel, Renate, Schick, Ursula M, Nolte, Ilja M, Kraja, Aldi, Hsu, Yi-Hsiang, Tylee, Daniel S, Zwicker, Alyson, Uher, Rudolf, Davey-Smith, George, Morrison, Alanna C, Hicks, Andrew, van Duijn, Cornelia M, Ward-Caviness, Cavin, Boerwinkle, Eric, Rotter, J, Rice, Ken, Lange, Leslie, Perola, Markus, de Geus, Eco, Morris, Andrew P, Makela, Kari Matti, Stacey, David, Eriksson, Johan, Frayling, Tim M, Slagboom, Eline P, and Livshits, Gregory
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Aging ,Autoimmune Disease ,Arthritis ,Osteoporosis ,Human Genome ,Heart Disease ,Cardiovascular ,Rheumatoid Arthritis ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Arthritis ,Rheumatoid ,C-Reactive Protein ,Genome-Wide Association Study ,Humans ,Inflammation ,Mendelian Randomization Analysis ,Polymorphism ,Single Nucleotide ,CHARGE Inflammation Working Group ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes while additionally considering an inflammatory component, C-reactive protein (CRP). Genome-wide association study summary statistics were acquired from the GEnetic Factors for OSteoporosis Consortium, Cohorts for Heart and Aging Research Consortium and UK Biobank. Mendelian randomization (MR) was used to detect the presence of causal relationships. Colocalization analysis was performed to determine shared genetic variants between CRP and OP phenotypes. Analysis of pleiotropy between traits owing to shared causal single nucleotide polymorphisms (SNPs) was performed using PL eiotropic A nalysis under CO mposite null hypothesis (PLACO). MR analysis was suggestive of horizontal pleiotropy between RA and OP traits. RA was a significant causal risk factor for CRP (β = 0.027, 95% confidence interval = 0.016-0.038). There was no evidence of CRP→OP causal relationship, but horizontal pleiotropy was apparent. Colocalization established shared genomic regions between CRP and OP, including GCKR and SERPINA1 genes. Pleiotropy arising from shared causal SNPs revealed through the colocalization analysis was all confirmed by PLACO. These genes were found to be involved in the same molecular function 'protein binding' (GO:0005515) associated with RA, OP and CRP. We identified three major components explaining the epidemiological relationship among RA, OP and inflammation: (1) Pleiotropy explains a portion of the shared genetic relationship between RA and OP, albeit polygenically; (2) RA contributes to CRP elevation and (3) CRP, which is influenced by RA, demonstrated pleiotropy with OP.
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- 2022
5. Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics
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Kananen, Laura, Hurme, Mikko, Bürkle, Alexander, Moreno-Villanueva, Maria, Bernhardt, Jürgen, Debacq-Chainiaux, Florence, Grubeck-Loebenstein, Beatrix, Malavolta, Marco, Basso, Andrea, Piacenza, Francesco, Collino, Sebastiano, Gonos, Efstathios S., Sikora, Ewa, Gradinaru, Daniela, Jansen, Eugene H. J. M., Dollé, Martijn E. T., Salmon, Michel, Stuetz, Wolfgang, Weber, Daniela, Grune, Tilman, Breusing, Nicolle, Simm, Andreas, Capri, Miriam, Franceschi, Claudio, Slagboom, Eline, Talbot, Duncan, Libert, Claude, Raitanen, Jani, Koskinen, Seppo, Härkänen, Tommi, Stenholm, Sari, Ala-Korpela, Mika, Lehtimäki, Terho, Raitakari, Olli T., Ukkola, Olavi, Kähönen, Mika, Jylhä, Marja, and Jylhävä, Juulia
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- 2023
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6. RNNs on Monitoring Physical Activity Energy Expenditure in Older People
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Paraschiakos, Stylianos, de Sá, Cláudio Rebelo, Okai, Jeremiah, Slagboom, Eline P., Beekman, Marian, and Knobbe, Arno
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Electrical Engineering and Systems Science - Signal Processing ,Computer Science - Human-Computer Interaction ,Computer Science - Machine Learning - Abstract
Through the quantification of physical activity energy expenditure (PAEE), health care monitoring has the potential to stimulate vital and healthy ageing, inducing behavioural changes in older people and linking these to personal health gains. To be able to measure PAEE in a monitoring environment, methods from wearable accelerometers have been developed, however, mainly targeted towards younger people. Since elderly subjects differ in energy requirements and range of physical activities, the current models may not be suitable for estimating PAEE among the elderly. Because past activities influence present PAEE, we propose a modeling approach known for its ability to model sequential data, the Recurrent Neural Network (RNN). To train the RNN for an elderly population, we used the GOTOV dataset with 34 healthy participants of 60 years and older (mean 65 years old), performing 16 different activities. We used accelerometers placed on wrist and ankle, and measurements of energy counts by means of indirect calorimetry. After optimization, we propose an architecture consisting of an RNN with 3 GRU layers and a feedforward network combining both accelerometer and participant-level data. In this paper, we describe our efforts to go beyond the standard facilities of a GRU-based RNN, with the aim of achieving accuracy surpassing the state of the art. These efforts include switching aggregation function from mean to dispersion measures (SD, IQR, ...), combining temporal and static data (person-specific details such as age, weight, BMI) and adding symbolic activity data as predicted by a previously trained ML model. The resulting architecture manages to increase its performance by approximatelly 10% while decreasing training input by a factor of 10. It can thus be employed to investigate associations of PAEE with vitality parameters related to metabolic and cognitive health and mental well-being., Comment: For a revised, updated and published version (Jan 2022, open access) refer to the Journal of Data Mining and Knowledge Discovery, DOI https://doi.org/10.1007/s10618-021-00817-w. To make our experiments, scripts and results accessible to other researchers (open-source) we shared our scripts with the published version (Jan 2022)
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- 2020
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7. Cerebral small vessel disease genomics and its implications across the lifespan.
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Sargurupremraj, Muralidharan, Suzuki, Hideaki, Jian, Xueqiu, Sarnowski, Chloé, Evans, Tavia E, Bis, Joshua C, Eiriksdottir, Gudny, Sakaue, Saori, Terzikhan, Natalie, Habes, Mohamad, Zhao, Wei, Armstrong, Nicola J, Hofer, Edith, Yanek, Lisa R, Hagenaars, Saskia P, Kumar, Rajan B, van den Akker, Erik B, McWhirter, Rebekah E, Trompet, Stella, Mishra, Aniket, Saba, Yasaman, Satizabal, Claudia L, Beaudet, Gregory, Petit, Laurent, Tsuchida, Ami, Zago, Laure, Schilling, Sabrina, Sigurdsson, Sigurdur, Gottesman, Rebecca F, Lewis, Cora E, Aggarwal, Neelum T, Lopez, Oscar L, Smith, Jennifer A, Valdés Hernández, Maria C, van der Grond, Jeroen, Wright, Margaret J, Knol, Maria J, Dörr, Marcus, Thomson, Russell J, Bordes, Constance, Le Grand, Quentin, Duperron, Marie-Gabrielle, Smith, Albert V, Knopman, David S, Schreiner, Pamela J, Evans, Denis A, Rotter, Jerome I, Beiser, Alexa S, Maniega, Susana Muñoz, Beekman, Marian, Trollor, Julian, Stott, David J, Vernooij, Meike W, Wittfeld, Katharina, Niessen, Wiro J, Soumaré, Aicha, Boerwinkle, Eric, Sidney, Stephen, Turner, Stephen T, Davies, Gail, Thalamuthu, Anbupalam, Völker, Uwe, van Buchem, Mark A, Bryan, R Nick, Dupuis, Josée, Bastin, Mark E, Ames, David, Teumer, Alexander, Amouyel, Philippe, Kwok, John B, Bülow, Robin, Deary, Ian J, Schofield, Peter R, Brodaty, Henry, Jiang, Jiyang, Tabara, Yasuharu, Setoh, Kazuya, Miyamoto, Susumu, Yoshida, Kazumichi, Nagata, Manabu, Kamatani, Yoichiro, Matsuda, Fumihiko, Psaty, Bruce M, Bennett, David A, De Jager, Philip L, Mosley, Thomas H, Sachdev, Perminder S, Schmidt, Reinhold, Warren, Helen R, Evangelou, Evangelos, Trégouët, David-Alexandre, International Network against Thrombosis (INVENT) Consortium, International Headache Genomics Consortium (IHGC), Ikram, Mohammad A, Wen, Wei, DeCarli, Charles, Srikanth, Velandai K, Jukema, J Wouter, Slagboom, Eline P, and Kardia, Sharon LR
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International Network against Thrombosis (INVENT) Consortium ,International Headache Genomics Consortium ,Humans ,Alzheimer Disease ,Hypertension ,Medical History Taking ,Risk Assessment ,Risk Factors ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Stroke ,Genome-Wide Association Study ,Young Adult ,Diffusion Tensor Imaging ,Genetic Loci ,Mendelian Randomization Analysis ,Cerebral Small Vessel Diseases ,White Matter ,and over - Abstract
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
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- 2020
8. Metabolomic profiles predict individual multidisease outcomes
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Buergel, Thore, Steinfeldt, Jakob, Ruyoga, Greg, Pietzner, Maik, Bizzarri, Daniele, Vojinovic, Dina, Upmeier zu Belzen, Julius, Loock, Lukas, Kittner, Paul, Christmann, Lara, Hollmann, Noah, Strangalies, Henrik, Braunger, Jana M., Wild, Benjamin, Chiesa, Scott T., Spranger, Joachim, Klostermann, Fabian, van den Akker, Erik B., Trompet, Stella, Mooijaart, Simon P., Sattar, Naveed, Jukema, J. Wouter, Lavrijssen, Birgit, Kavousi, Maryam, Ghanbari, Mohsen, Ikram, Mohammad A., Slagboom, Eline, Kivimaki, Mika, Langenberg, Claudia, Deanfield, John, Eils, Roland, and Landmesser, Ulf
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- 2022
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9. Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
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van der Lee, Sven J, Conway, Olivia J, Jansen, Iris, Carrasquillo, Minerva M, Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R, Stringa, Najada, Chen, Jason A, Zettergren, Anna, Andlauer, Till FM, Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E, Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J, Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A, Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart NM, Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, Boeve, Bradley F, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel JT, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande AL, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild IA, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, Clarimón, Jordi, Christensen, Kaare, Ertekin-Taner, Nilüfer, Scholz, Sonja W, Ramirez, Alfredo, Ruiz, Agustín, Slagboom, Eline, and van der Flier, Wiesje M
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Biomedical and Clinical Sciences ,Neurosciences ,Dementia ,Aging ,Acquired Cognitive Impairment ,Parkinson's Disease ,Alzheimer's Disease ,Genetics ,Neurodegenerative ,Brain Disorders ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,DESGESCO ,EADB ,IFGC ,IPDGC ,RiMod-FTD ,Netherlands Brain Bank ,GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.
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- 2020
10. A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
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van der Lee, Sven J, Conway, Olivia J, Jansen, Iris, Carrasquillo, Minerva M, Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R, Stringa, Najada, Chen, Jason A, Zettergren, Anna, Andlauer, Till FM, Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E, Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J, Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A, Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart NM, Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, Boeve, Bradley F, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel JT, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande AL, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild IA, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, Clarimón, Jordi, Christensen, Kaare, Ertekin-Taner, Nilüfer, Scholz, Sonja W, Ramirez, Alfredo, Ruiz, Agustín, Slagboom, Eline, and van der Flier, Wiesje M
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Biomedical and Clinical Sciences ,Neurosciences ,Rare Diseases ,Acquired Cognitive Impairment ,Alzheimer's Disease ,Neurodegenerative ,Alzheimer's Disease Related Dementias (ADRD) ,Brain Disorders ,Dementia ,Clinical Research ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Prevention ,Aging ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Alleles ,Alzheimer Disease ,Amyotrophic Lateral Sclerosis ,Brain ,Frontotemporal Dementia ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Lewy Body Disease ,Longevity ,Microglia ,Multiple Sclerosis ,Mutation ,Neuroimaging ,Parkinson Disease ,Phospholipase C gamma ,Risk ,Alzheimer's disease ,Frontotemporal dementia ,Dementia with Lewy bodies ,Progressive supranuclear palsy ,Parkinson's disease ,Amyotrophic lateral sclerosis ,Multiple sclerosis ,Neurodegenerative disease ,PLCG2 ,Phospholipase C Gamma 2 ,DESGESCO (Dementia Genetics Spanish Consortium) ,EADB ,EADB ,IFGC (International FTD-Genomics Consortium) ,IPDGC ,IPDGC ,RiMod-FTD ,Netherlands Brain Bank ,GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group ,Alzheimer’s disease ,Parkinson’s disease ,frontotemporal dementia ,dementia with Lewy-bodies ,progressive suprauclear palsy ,Parkinson's Disease ,amyotrophic lateral sclerosis ,multiple sclerosis ,neurodegenerative disease ,longevity ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.
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- 2019
11. Secondary Phenotype Analysis in Ascertained Family Designs: Application to the Leiden Longevity Study
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Tissier, Renaud, Tsonaka, Roula, Mooijaart, Simon P., Slagboom, Eline, and Houwing-Duistermaat, Jeanine J.
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Statistics - Applications - Abstract
The case-control design is often used to test associations between the case-control status and genetic variants. In addition to this primary phenotype a number of additional traits, known as secondary phenotypes, are routinely recorded and typically associations between genetic factors and these secondary traits are studied too. Analysing secondary phenotypes in case-control studies may lead to biased genetic effect estimates, especially when the marker tested is associated with the primary phenotype and when the primary and secondary phenotypes tested are correlated. Several methods have been proposed in the literature to overcome the problem but they are limited to case-control studies and not directly applicable to more complex designs, such as the multiple-cases family studies. A proper secondary phenotype analysis, in this case, is complicated by the within families correlations on top of the biased sampling design. We propose a novel approach to accommodate the ascertainment process while explicitly modelling the familial relationships. Our approach pairs existing methods for mixed-effects models with the retrospective likelihood framework and uses a multivariate probit model to capture the association between the mixed type primary and secondary phenotypes. To examine the efficiency and bias of the estimates we performed simulations under several scenarios for the association between the primary phenotype, secondary phenotype, and genetic markers. We will illustrate the method by analysing the association between triglyceride levels and glucose (secondary phenotypes) and genetic markers from the Leiden Longevity study, a multiple-cases family study that investigates longevity.
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- 2016
12. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
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Jiang, Xia, O’Reilly, Paul F, Aschard, Hugues, Hsu, Yi-Hsiang, Richards, J Brent, Dupuis, Josée, Ingelsson, Erik, Karasik, David, Pilz, Stefan, Berry, Diane, Kestenbaum, Bryan, Zheng, Jusheng, Luan, Jianan, Sofianopoulou, Eleni, Streeten, Elizabeth A, Albanes, Demetrius, Lutsey, Pamela L, Yao, Lu, Tang, Weihong, Econs, Michael J, Wallaschofski, Henri, Völzke, Henry, Zhou, Ang, Power, Chris, McCarthy, Mark I, Michos, Erin D, Boerwinkle, Eric, Weinstein, Stephanie J, Freedman, Neal D, Huang, Wen-Yi, Van Schoor, Natasja M, van der Velde, Nathalie, Groot, Lisette CPGM de, Enneman, Anke, Cupples, L Adrienne, Booth, Sarah L, Vasan, Ramachandran S, Liu, Ching-Ti, Zhou, Yanhua, Ripatti, Samuli, Ohlsson, Claes, Vandenput, Liesbeth, Lorentzon, Mattias, Eriksson, Johan G, Shea, M Kyla, Houston, Denise K, Kritchevsky, Stephen B, Liu, Yongmei, Lohman, Kurt K, Ferrucci, Luigi, Peacock, Munro, Gieger, Christian, Beekman, Marian, Slagboom, Eline, Deelen, Joris, Heemst, Diana van, Kleber, Marcus E, März, Winfried, de Boer, Ian H, Wood, Alexis C, Rotter, Jerome I, Rich, Stephen S, Robinson-Cohen, Cassianne, den Heijer, Martin, Jarvelin, Marjo-Riitta, Cavadino, Alana, Joshi, Peter K, Wilson, James F, Hayward, Caroline, Lind, Lars, Michaëlsson, Karl, Trompet, Stella, Zillikens, M Carola, Uitterlinden, Andre G, Rivadeneira, Fernando, Broer, Linda, Zgaga, Lina, Campbell, Harry, Theodoratou, Evropi, Farrington, Susan M, Timofeeva, Maria, Dunlop, Malcolm G, Valdes, Ana M, Tikkanen, Emmi, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Raitakari, Olli T, Mikkilä, Vera, Ikram, M Arfan, Sattar, Naveed, Jukema, J Wouter, Wareham, Nicholas J, Langenberg, Claudia, Forouhi, Nita G, Gundersen, Thomas E, Khaw, Kay-Tee, Butterworth, Adam S, Danesh, John, and Spector, Timothy
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Amidohydrolases ,Autoimmune Diseases ,Cohort Studies ,Female ,Genome-Wide Association Study ,Humans ,Male ,Polymorphism ,Single Nucleotide ,Vesicular Transport Proteins ,Vitamin D ,White People - Abstract
Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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- 2018
13. Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis.
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Castaño-Betancourt, Martha C, Evans, Dan S, Ramos, Yolande FM, Boer, Cindy G, Metrustry, Sarah, Liu, Youfang, den Hollander, Wouter, van Rooij, Jeroen, Kraus, Virginia B, Yau, Michelle S, Mitchell, Braxton D, Muir, Kenneth, Hofman, Albert, Doherty, Michael, Doherty, Sally, Zhang, Weiya, Kraaij, Robert, Rivadeneira, Fernando, Barrett-Connor, Elizabeth, Maciewicz, Rose A, Arden, Nigel, Nelissen, Rob GHH, Kloppenburg, Margreet, Jordan, Joanne M, Nevitt, Michael C, Slagboom, Eline P, Hart, Deborah J, Lafeber, Floris, Styrkarsdottir, Unnur, Zeggini, Eleftheria, Evangelou, Evangelos, Spector, Tim D, Uitterlinden, Andre G, Lane, Nancy E, Meulenbelt, Ingrid, Valdes, Ana M, and van Meurs, Joyce BJ
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Cartilage ,Hip Joint ,Humans ,Osteoarthritis ,Hip ,Genetic Predisposition to Disease ,Trehalase ,Transforming Growth Factor alpha ,Regulatory Sequences ,Nucleic Acid ,Genetic Heterogeneity ,Polymorphism ,Single Nucleotide ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Receptor ,Fibroblast Growth Factor ,Type 3 ,Genome-Wide Association Study ,Phosphatidylinositol 3-Kinases ,Class Ia Phosphatidylinositol 3-Kinase ,Osteoarthritis ,Hip ,Regulatory Sequences ,Nucleic Acid ,Polymorphism ,Single Nucleotide ,and over ,Receptor ,Fibroblast Growth Factor ,Type 3 ,Genetics ,Developmental Biology - Abstract
Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10-8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies.
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- 2016
14. Federated BrainAge estimation from MRI: a proof of concept
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Mateus, Pedro, primary, Yu, Jing, additional, Garst, Swier J.F., additional, Harms, Alexander G.J., additional, Cats, Davy, additional, Delgado, Inigo Bermejo, additional, Roshchupkin, Gennady V., additional, Reinders, Marcel JT, additional, Slagboom, Eline, additional, Mei, Haillang, additional, and Bron, Esther E, additional
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- 2023
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15. Identified senescence endotypes in aged cartilage are reflected in the blood metabolome
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Boone, Ilja, primary, Tuerlings, Margo, additional, Coutinho de Almeida, Rodrigo, additional, Lehmann, Johannes, additional, Ramos, Yolande, additional, Nelissen, Rob, additional, Slagboom, Eline, additional, de Keizer, Peter, additional, and Meulenbelt, Ingrid, additional
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- 2023
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16. Improved selection of participants in genetic longevity studies: family scores revisited
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Rodríguez-Girondo, Mar, van den Berg, Niels, Hof, Michel H., Beekman, Marian, and Slagboom, Eline
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- 2021
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17. OTTERS:a powerful TWAS framework leveraging summary-level reference data
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Dai, Qile, Zhou, Geyu, Zhao, Hongyu, Võsa, Urmo, Franke, Lude, Battle, Alexis, Teumer, Alexander, Lehtimäki, Terho, Raitakari, Olli T., Esko, Tõnu, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Favé, Marie-Julie, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Epstein, Michael P., Yang, Jingjing, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Biological Psychology, Amsterdam Reproduction & Development, APH - Methodology, APH - Personalized Medicine, Internal Medicine, Tampere University, Department of Clinical Chemistry, and Clinical Medicine
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Multidisciplinary ,1182 Biochemistry, cell and molecular biology ,General Physics and Astronomy ,3111 Biomedicine ,General Chemistry ,Medical Genetics ,General Biochemistry, Genetics and Molecular Biology ,Medicinsk genetik - Abstract
Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies. Godkänd;2023;Nivå 0;2023-04-06 (hanlid);Funder: for more funders see the article https://doi.org/10.1038/s41467-023-36862-w
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- 2023
18. Broad phenotype of cysteine altering NOTCH3 variants in UK Biobank: CADASIL to non-penetrance
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Rutten, Julie W., Hack, Remco J., Duering, Marco, Gravesteijn, Gido G., Dauwerse, Johannes G., Overzier, Maurice, van den Akker, Erik B., Slagboom, Eline, Holstege, Henne, Nho, Kwangsik, Saykin, Andrew, Dichgans, Martin, Malik, Rainer, and Lesnik Oberstein, Saskia A.J.
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- 2020
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19. Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis
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Kerkhof, Hanneke JM, Meulenbelt, Ingrid, Carr, Andrew, Gonzalez, Antonio, Hart, Deborah, Hofman, Albert, Kloppenburg, Margreet, Lane, Nancy E, Loughlin, John, Nevitt, Michael C, Pols, Huibert AP, Rivadeneira, Fernando, Slagboom, Eline P, Spector, Tim D, Stolk, Lisette, Tsezou, Aspasia, Uitterlinden, André G, Valdes, Ana M, and van Meurs, Joyce BJ
- Abstract
Abstract Background The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis. Methods In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively. Fixed- and random-effects meta-analyses were performed over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases and approximately 6000 controls. Results The C allele of rs1256031 was associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I (OR 1.36, 95% CI 1.08-1.70, p = 0.009). Haplotype analysis and analysis of knee- and hand OA did not give additional information. With the replication studies, the meta-analysis did not show a significant effect of this SNP on hip OA in the total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10). Stratification according to gender did not change the results. In this study, we had 80% power to detect an odds ratio of at least 1.14 for hip OA (α = 0.05). Conclusion This study showed that common genetic variation in the ESR2 gene is not likely to influence the risk of osteoarthritis with effects smaller than a 13% increase.
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- 2010
20. Automated quantification of metabolites in blood-derived samples by NMR
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Verhoeven, Aswin, Slagboom, Eline, Wuhrer, Manfred, Giera, Martin, and Mayboroda, Oleg A.
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- 2017
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21. Epigenome-Wide Association Study Reveals CpG Sites Associated with Thyroid Function and Regulatory Effects on KLF9
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Weihs, Antoine, primary, Chaker, Layal, additional, Martin, Tiphaine C., additional, Braun, Kim V.E., additional, Campbell, Purdey J., additional, Cox, Simon R., additional, Fornage, Myriam, additional, Gieger, Christian, additional, Grabe, Hans J., additional, Grallert, Harald, additional, Harris, Sarah E., additional, Kühnel, Brigitte, additional, Marioni, Riccardo E., additional, Martin, Nicholas G., additional, McCartney, Daniel L., additional, McRae, Allan F., additional, Meisinger, Christa, additional, van Meurs, Joyce B.J., additional, Nano, Jana, additional, Nauck, Matthias, additional, Peters, Annette, additional, Prokisch, Holger, additional, Roden, Michael, additional, Selvin, Elizabeth, additional, Beekman, Marian, additional, van Heemst, Diana, additional, Slagboom, Eline P., additional, Swenson, Brenton R., additional, Tin, Adrienne, additional, Tsai, Pei-Chien, additional, Uitterlinden, Andre, additional, Visser, W. Edward, additional, Völzke, Henry, additional, Waldenberger, Melanie, additional, Walsh, John P., additional, Köttgen, Anna, additional, Wilson, Scott G., additional, Peeters, Robin P., additional, Bell, Jordana T., additional, Medici, Marco, additional, and Teumer, Alexander, additional
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- 2023
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22. Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics
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Kananen, Laura, primary, Hurme, Mikko, additional, Bürkle, Alexander, additional, Moreno-Villanueva, Maria, additional, Bernhardt, Jürgen, additional, Debacq-Chainiaux, Florence, additional, Grubeck-Loebenstein, Beatrix, additional, Malavolta, Marco, additional, Basso, Andrea, additional, Piacenza, Francesco, additional, Collino, Sebastiano, additional, Gonos, Efstathios S., additional, Sikora, Ewa, additional, Gradinaru, Daniela, additional, Jansen, Eugene H. J. M., additional, Dollé, Martijn E. T., additional, Salmon, Michel, additional, Stuetz, Wolfgang, additional, Weber, Daniela, additional, Grune, Tilman, additional, Breusing, Nicolle, additional, Simm, Andreas, additional, Capri, Miriam, additional, Franceschi, Claudio, additional, Slagboom, Eline, additional, Talbot, Duncan, additional, Libert, Claude, additional, Raitanen, Jani, additional, Koskinen, Seppo, additional, Härkänen, Tommi, additional, Stenholm, Sari, additional, Ala-Korpela, Mika, additional, Lehtimäki, Terho, additional, Raitakari, Olli T., additional, Ukkola, Olavi, additional, Kähönen, Mika, additional, Jylhä, Marja, additional, and Jylhävä, Juulia, additional
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- 2022
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23. Twins and the fetal origins hypothesis: An application to growth data
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Boomsma, Dorret, Willemsen, Gonneke, de Geus, Eco, Kupper, Nina, Posthuma, Danielle, IJzerman, Richard, Heijmans, Bas, Slagboom, Eline, Beeml, Leo, Dolan, Conor, Kordon, Claude, editor, Gaillard, Rolf-Christian, editor, and Christen, Yves, editor
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- 2005
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24. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour
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Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda W. J. H., Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Jan Hottenga, Jouke, van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, van Heemst, Diana, van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Akimova, Evelina T., Bergmann, Sven, Boardman, Jason D., Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey-Smith, George, Davies, Gail, Deary, Ian J., Franco, Oscar, Gaskins, Audrey J., de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Grabe, Hans Jörgen, Gunderson, Erica P., Harris, Kathleen Mullan, Hartwig, Fernando P., He, Chunyan, Hill, W. David, Homuth, Georg, Horta, Bernando Lessa, Huang, Hongyang, Hyppӧnen, Elina, Ikram, M. Arfan, Johannesson, Magnus, Kamali, Zoha, Kavousi, Maryam, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, McQueen, Matthew B., Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Missmer, Stacey A., Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nolte, Ilja M., Noordam, Raymond, Peters, Annette, Power, Chris, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Stefánsson, Kári, Stöckl, Doris, Strauch, Konstantin, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Waldenberger, Melanie, Wareham, Nicholas J., Willemsen, Gonneke, Zhao, Jing Hau, Pers, Tune H., Snieder, Harold, Perry, John R. B., Ong, Ken K., den Hoed, Marcel, Barban, Nicola, Day, Felix R., Mills, M. C., Tropf, F. C., Brazel, D. M., van Zuydam, N., Vaez, A., Agbessi, M., Ahsan, H., Alves, I., Andiappan, A. K., Arindrarto, W., Awadalla, P., Battle, A., Beutner, F., Jan Bonder, M., Boomsma, D. I., Christiansen, M. W., Claringbould, A., Deelen, P., Esko, T., Fave, M. -J., Franke, L., Frayling, T., Gharib, S. A., Gibson, G., Heijmans, B. T., Hemani, G., Jansen, R., Kahonen, M., Kalnapenkis, A., Kasela, S., Kettunen, J., Kim, Y., Kirsten, H., Kovacs, P., Krohn, K., Kronberg, J., Kukushkina, V., Kutalik, Z., Lee, B., Lehtimaki, T., Loeffler, M., Marigorta, U. M., Mei, H., Milani, L., Montgomery, G. W., Muller-Nurasyid, M., Nauck, M., Nivard, M. G., Penninx, B. W. J. H., Perola, M., Pervjakova, N., Pierce, B. L., Powell, J., Prokisch, H., Psaty, B. M., Raitakari, O. T., Ripatti, S., Rotzschke, O., Rueger, S., Saha, A., Scholz, M., Schramm, K., Seppala, I., Slagboom, E. P., Stehouwer, C. D. A., Stumvoll, M., Sullivan, P., 't Hoen, P. A. C., Teumer, A., Thiery, J., Tong, L., Tonjes, A., van Dongen, J., van Iterson, M., van Meurs, J., Veldink, J. H., Verlouw, J., Visscher, P. M., Volker, U., Vosa, U., Westra, H. -J., Wijmenga, C., Yaghootkar, H., Yang, J., Zeng, B., Zhang, F., van Greevenbroek, M. M. J., Schalkwijk, C. G., Deelen, J., van Heemst, D., van Duijn, C. M., Hofman, B. A., Isaacs, A., Uitterlinden, A. G., Verbiest, M., Suchiman, H. E. D., Verkerk, M., van der Breggen, R., van Rooij, J., Lakenberg, N., Bot, J., Zhernakova, D. V., Luijk, R., Bonder, M. J., Swertz, M. A., van Zwet, E. W., Akimova, E. T., Bergmann, S., Boardman, J. D., Buring, J. E., Cesarini, D., Chasman, D. I., Chavarro, J. E., Cocca, M., Concas, M. P., Davey-Smith, G., Davies, G., Deary, I. J., Gaskins, A. J., de Geus, E. J. C., Gieger, C., Girotto, G., Grabe, H. J., Gunderson, E. P., Harris, K. M., Hartwig, F. P., He, C., Homuth, G., Horta, B. L., Jan Hottenga, J., Huang, H., Hyppӧnen, E., Ikram, M. A., Johannesson, M., Kamali, Z., Kavousi, M., Kraft, P., Kuhnel, B., Langenberg, C., Study, L. C., Lind, P. A., Luan, J., Magi, R., Magnusson, P. K. E., Mahajan, A., Martin, N. G., Mbarek, H., Mccarthy, M. I., Mcmahon, G., Mcqueen, M. B., Medland, S. E., Meitinger, T., Metspalu, A., Mihailov, E., Missmer, S. A., Mollegaard, S., Mook-Kanamori, D. O., Morgan, A., van der Most, P. J., de Mutsert, R., Noordam, R., Power, C., Redmond, P., Rich-Edwards, J. W., Ridker, P. M., Rietveld, C. A., Ring, S. M., Rose, L. M., Rueedi, R., Stefansson, K., Stockl, D., Strauch, K., Thurik, A. R., Timpson, N. J., Turman, C., Wareham, N. J., Willemsen, G., Zhao, J. H., Pers, T. H., Snieder, H., Perry, J. R. B., Ong, K. K., den Hoed, M., Barban, N., Day, F. R., Mills, Melinda C, Tropf, Felix C, Brazel, David M, van Zuydam, Natalie, Vaez, Ahmad, Pers, Tune H, Snieder, Harold, Perry, John RB, Ong, Ken K, den Hoed, Marcel, Barban, Nicola, Day, Felix R, Hyppӧnen, Elina, eQTLGen Consortium, BIOS Consortium, Human Reproductive Behaviour Consortium, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Consortium, eQTLGen, Consortium, BIOS, Consortium, Human Reproductive Behaviour, Mahajan, A, McCarthy, MI, Mills, Melinda C., Tropf, Felix C., Brazel, David M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexi, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johanne, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Marku, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthia, Nivard, Michel G., Penninx, Brenda W. J. H., Perola, Marku, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashi, Scholz, Marku, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Jan Hottenga, Jouke, van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Jori, van Heemst, Diana, van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Nooren, Irene, Moed, Matthij, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Akimova, Evelina T., Bergmann, Sven, Boardman, Jason D., Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey-Smith, George, Davies, Gail, Deary, Ian J., Franco, Oscar, Gaskins, Audrey J., de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Grabe, Hans Jörgen, Gunderson, Erica P., Harris, Kathleen Mullan, Hartwig, Fernando P., He, Chunyan, Hill, W. David, Homuth, Georg, Horta, Bernando Lessa, Huang, Hongyang, Ikram, M. Arfan, Johannesson, Magnu, Kamali, Zoha, Kavousi, Maryam, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, McQueen, Matthew B., Medland, Sarah E., Meitinger, Thoma, Metspalu, Andre, Mihailov, Evelin, Missmer, Stacey A., Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nolte, Ilja M., Noordam, Raymond, Peters, Annette, Power, Chri, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Stefánsson, Kári, Stöckl, Dori, Strauch, Konstantin, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Waldenberger, Melanie, Wareham, Nicholas J., Willemsen, Gonneke, Zhao, Jing Hau, Pers, Tune H., Perry, John R. B., Ong, Ken K., Day, Felix R., Sociology [until 2010], Biological Psychology, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Management and Organisation, Urology, Medical Informatics, Department of Marketing Management, Epidemiology, Internal Medicine, Radiology & Nuclear Medicine, Neurology, Applied Economics, and Life Course Epidemiology (LCE)
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Male ,demography ,genetic variants ,reproductive biology ,externalising behavior ,environmental effects ,Disease ,Genome-wide association studies ,Behavioral Neuroscience ,0302 clinical medicine ,genetics ,media_common ,fertility ,0303 health sciences ,Reproduction ,Incidence (epidemiology) ,Coitus ,Age Factors ,Longevity ,sexual intercourse ,health ,Spermatid differentiation ,Single Nucleotide ,Reproduction/genetics ,3. Good health ,Behavioural genetics ,Parturition/genetics ,Female ,infertility ,Infertility ,genetic variant ,Adolescent ,Social Psychology ,media_common.quotation_subject ,Experimental and Cognitive Psychology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Reproductive biology ,medicine ,Humans ,Polymorphism ,behavioural genetics ,first sexual intercourse ,Genetic Association Studies ,Demography ,030304 developmental biology ,Parturition ,Coitus/physiology ,medicine.disease ,externalising behaviour ,Sexual intercourse ,Fertility ,age ,030217 neurology & neurosurgery ,first birth - Abstract
Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4–14%] for women born in 1940 to 22% [CI = 19–25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.
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- 2021
25. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity
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Wahl, Simone, Drong, Alexander, Lehne, Benjamin, Loh, Marie, Scott, William R., Kunze, Sonja, Tsai, Pei-Chien, Ried, Janina S., Zhang, Weihua, Yang, Youwen, Tan, Sili, Fiorito, Giovanni, Franke, Lude, Guarrera, Simonetta, Kasela, Silva, Kriebel, Jennifer, Richmond, Rebecca C., Adamo, Marco, Afzal, Uzma, Ala-Korpela, Mika, Albetti, Benedetta, Ammerpohl, Ole, Apperley, Jane F., Beekman, Marian, Bertazzi, Pier Alberto, Black, Lucas S., Blancher, Christine, Bonder, Marc-Jan, Brosch, Mario, Carstensen-Kirberg, Maren, de Craen, Anton J. M., de Lusignan, Simon, Dehghan, Abbas, Elkalaawy, Mohamed, Fischer, Krista, Franco, Oscar H., Gaunt, Tom R., Hampe, Jochen, Hashemi, Majid, Isaacs, Aaron, Jenkinson, Andrew, Jha, Sujeet, Kato, Norihiro, Krogh, Vittorio, Laffan, Michael, Meisinger, Christa, Meitinger, Thomas, Mok, Zuan Yu, Motta, Valeria, Ng, Hong Kiat, Nikolakopoulou, Zacharoula, Nteliopoulos, Georgios, Panico, Salvatore, Pervjakova, Natalia, Prokisch, Holger, Rathmann, Wolfgang, Roden, Michael, Rota, Federica, Rozario, Michelle Ann, Sandling, Johanna K., Schafmayer, Clemens, Schramm, Katharina, Siebert, Reiner, Slagboom, Eline P., Soininen, Pasi, Stolk, Lisette, Strauch, Konstantin, Tai, E-Shyong, Tarantini, Letizia, Thorand, Barbara, Tigchelaar, Ettje F., Tumino, Rosario, Uitterlinden, Andre G., van Duijn, Cornelia, van Meurs, Joyce B. J., Vineis, Paolo, Wickremasinghe, Ananda Rajitha, Wijmenga, Cisca, Yang, Tsun-Po, Yuan, Wei, Zhernakova, Alexandra, Batterham, Rachel L., Smith, George Davey, Deloukas, Panos, Heijmans, Bastiaan T., Herder, Christian, Hofman, Albert, Lindgren, Cecilia M., Milani, Lili, van der Harst, Pim, Peters, Annette, Illig, Thomas, Relton, Caroline L., Waldenberger, Melanie, Jürvelin, Marjo-Riitta, Bollati, Valentina, Soong, Richie, Spector, Tim D., Scott, James, McCarthy, Mark I., Elliott, Paul, Bell, Jordana T., Matullo, Giuseppe, Gieger, Christian, Kooner, Jaspal S., Grallert, Harald, and Chambers, John C.
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- 2017
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26. Integrating Protein-Protein Interaction Networks with Gene- Gene Co-Expression Networks improves Gene Signatures for Classifying Breast Cancer Metastasis
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Akker Erik van den, Verbruggen Bas, Heijmans Bas, Beekman Marian, Kok Joost, Slagboom Eline, and Reinders Marcel
- Subjects
Biotechnology ,TP248.13-248.65 - Abstract
Multiple studies have illustrated that gene expression profiling of primary breast cancers throughout the final stages of tumor development can provide valuable markers for risk prediction of metastasis and disease sub typing. However, the identification of a biologically interpretable and universally shared set of markers proved to be difficult. Here, we propose a method for de novo grouping of genes by dissecting the proteinprotein interaction network into disjoint sub networks using pair wise gene expression correlation measures. We show that the obtained sub networks are functionally coherent and are consistently identified when applied on a compendium composed of six different breast cancer studies. Application of the proposed method using different integration approaches underlines the robustness of the identified sub network related to cell cycle and identifies putative new sub network markers for metastasis related to cell-cell adhesion, the proteasome complex and JUN-FOS signalling. Although gene selection with the proposed method does not directly improve upon previously reported cross study classification performances, it shows great promises for applications in data integration and result interpretation.
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- 2011
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27. De Leiden Lang Leven Studie: weerspiegelt het brein een lang leven?
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Altmann-Schneider, Irmhild, van der Grond, Jeroen, van den Berg-Huysmans, Annette, de Craen, Anton, Slagboom, Eline, Westendorp, Rudi, and van Buchem, Mark
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- 2013
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28. Quantifying physical activity in older people to study healthy ageing, the GOTO study
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Paraschiakos, Stylianos, Knobbe, Arno, Slagboom, Eline, and Beekman, Marian
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humanities - Abstract
ICAMPAM 2021 Poster presentation: Quantifying activity to study healthy ageing landscape While, nowadays, people generally live longer, they are increasingly facing health issues, leading to a reduction in functionality and quality of life along with an increase in medical costs. Sedentary lifestyles among the elderly mount to 10 hrs inactivity per day. Hence combined caloric intake/physical activity interventions are applied to encourage the elderly to follow a more active and healthy lifestyle. These need to be carefully monitored. The Growing Old TOgether (GOTO) study introduces such an intervention, where a 13-weeks lifestyle program was applied, with a target of 12.5% caloric restriction and 12.5% increase in energy expenditure through an increase in physical activity, in 164 older adults (mean age=63.2 years; BMI=23-35 kg/m2). Quantifying the changes in physical behaviour is of utmost importance in order to investigate their effect on health gains. Using data from wrist and ankle activity accelerometers (wearables) and machine learning models, we were able to recognize the different activities performed and to report their frequencies and durations both in baseline and after the 13-weeks intervention. To quantify these observations, we built activity profiles that we intend to associate with changes in physiological parameters of health. References: [1] van de Rest et al. 2016. Metabolic effects of a 13-weeks lifestyle intervention in older adults: The Growing Old Together Study. Aging (Albany NY). DOI: https://doi.org/10.18632/aging.100877 [2] GOTOV Human Physical Activity and Energy Expenditure Dataset on Older Individuals, 4TU.ResearchData. Dataset. DOI: https://doi.org/10.4121/uuid:d3dd8165... [3] S.Paraschiakos et al. 2020. Activity recognition using wearable sensors for tracking the elderly. DOI: https://doi.org/10.1007/s11257-020-09... [4] S. Paraschiakos, et al. 2020 Preprint. RNNs on Monitoring Physical Activity Energy Expenditure in Older People. DOI: https://arxiv.org/abs/2006.01169
- Published
- 2021
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29. Transcriptional Associations of Osteoarthritis-Mediated Loss of Epigenetic Control in Articular Cartilage
- Author
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den Hollander, Wouter, Ramos, Yolande F. M., Bomer, Nils, Elzinga, Stefan, van der Breggen, Ruud, Lakenberg, Nico, de Dijcker, Wesley J., Suchiman, Eka H. D., Duijnisveld, Bouke J., Houwing-Duistermaat, Jeanine J., Slagboom, Eline P., Bos, Steffan D., Nelissen, Rob G. H. H., and Meulenbelt, Ingrid
- Published
- 2015
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30. Genetically determined prospect to become long-lived is associated with less abdominal fat and in particular less abdominal visceral fat in men
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Sala, Michiel L., Röell, Boudewijn, van der Bijl, Noortje, van der Grond, Jeroen, de Craen, Anton J. M., Slagboom, Eline P., van der Geest, Rob, de Roos, Albert, and Kroft, Lucia J. M.
- Published
- 2015
- Full Text
- View/download PDF
31. An alternative approach to multiple testing for methylation QTL mapping reduces the proportion of falsely identified CpGs
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Luijk, René, Goeman, Jelle J., Slagboom, Eline P., Heijmans, Bastiaan T., and van Zwet, Erik W.
- Published
- 2015
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32. GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy
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Broer, Linda, Buchman, Aron S., Deelen, Joris, Evans, Daniel S., Faul, Jessica D., Lunetta, Kathryn L., Sebastiani, Paola, Smith, Jennifer A., Smith, Albert V., Tanaka, Toshiko, Yu, Lei, Arnold, Alice M., Aspelund, Thor, Benjamin, Emelia J., De Jager, Philip L., Eirkisdottir, Gudny, Evans, Denis A., Garcia, Melissa E., Hofman, Albert, Kaplan, Robert C., Kardia, Sharon L. R., Kiel, Douglas P., Oostra, Ben A., Orwoll, Eric S., Parimi, Neeta, Psaty, Bruce M., Rivadeneira, Fernando, Rotter, Jerome I., Seshadri, Sudha, Singleton, Andrew, Tiemeier, Henning, Uitterlinden, André G., Zhao, Wei, Bandinelli, Stefania, Bennett, David A., Ferrucci, Luigi, Gudnason, Vilmundur, Harris, Tamara B., Karasik, David, Launer, Lenore J., Perls, Thomas T., Slagboom, Eline P., Tranah, Gregory J., Weir, David R., Newman, Anne B., van Duijn, Cornelia M., and Murabito, Joanne M.
- Published
- 2015
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33. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
- Author
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Evangelou, Evangelos, Kerkhof, Hanneke J, Styrkarsdottir, Unnur, Ntzani, Evangelia E, Bos, Steffan D, Esko, Tonu, Evans, Daniel S, Metrustry, Sarah, Panoutsopoulou, Kalliope, Ramos, Yolande F M, Thorleifsson, Gudmar, Tsilidis, Konstantinos K, Arden, Nigel, Aslam, Nadim, Bellamy, Nicholas, Birrell, Fraser, Blanco, Francisco J, Carr, Andrew, Chapman, Kay, Day-Williams, Aaron G, Deloukas, Panos, Doherty, Michael, Engström, Gunnar, Helgadottir, Hafdis T, Hofman, Albert, Ingvarsson, Thorvaldur, Jonsson, Helgi, Keis, Aime, Keurentjes, Christiaan J, Kloppenburg, Margreet, Lind, Penelope A, McCaskie, Andrew, Martin, Nicholas G, Milani, Lili, Montgomery, Grant W, Nelissen, Rob G H H, Nevitt, Michael C, Nilsson, Peter M, Ollier, William ER, Parimi, Neeta, Rai, Ashok, Ralston, Stuart H, Reed, Mike R, Riancho, Jose A, Rivadeneira, Fernando, Rodriguez-Fontenla, Cristina, Southam, Lorraine, Thorsteinsdottir, Unnur, Tsezou, Aspasia, Wallis, Gillian A, Wilkinson, Mark J, Gonzalez, Antonio, Lane, Nancy E, Lohmander, Stefan L, Loughlin, John, Metspalu, Andres, Uitterlinden, Andre G, Jonsdottir, Ingileif, Stefansson, Kari, Slagboom, Eline P, Zeggini, Eleftheria, Meulenbelt, Ingrid, Ioannidis, John PA, Spector, Tim D, van Meurs, Joyce B J, and Valdes, Ana M
- Published
- 2014
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- View/download PDF
34. Associations between age and gray matter volume in anatomical brain networks in middle-aged to older adults
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Hafkemeijer, Anne, Altmann-Schneider, Irmhild, de Craen, Anton J. M., Slagboom, Eline P., van der Grond, Jeroen, and Rombouts, Serge A. R. B.
- Published
- 2014
- Full Text
- View/download PDF
35. MethylAid: visual and interactive quality control of large Illumina 450k datasets
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van Iterson, Maarten, Tobi, Elmar W., Slieker, Roderick C., den Hollander, Wouter, Luijk, René, Slagboom, Eline P., and Heijmans, Bastiaan T.
- Published
- 2014
- Full Text
- View/download PDF
36. A Common Mineralocorticoid Receptor Polymorphism (I180V) Interacts with Life Events in Relation to Perfectionism in Eating Disorders: A Pilot Study
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Slof-Opʼt Landt, Margarita C. T., DeRijk, Roel H., van Son, Gabrielle E., Suchiman, H. Eka D., Meulenbelt, Ingrid, Slagboom, Eline P., and Van Furth, Eric F.
- Published
- 2014
- Full Text
- View/download PDF
37. Lower proportion of naïve peripheral CD8+ T cells and an unopposed pro-inflammatory response to human Cytomegalovirus proteins in vitro are associated with longer survival in very elderly people
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Derhovanessian, Evelyna, Maier, Andrea B., Hähnel, Karin, Zelba, Henning, de Craen, Anton J. M., Roelofs, Helene, Slagboom, Eline P., Westendorp, Rudi G. J., and Pawelec, Graham
- Published
- 2013
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- View/download PDF
38. Age, Sex, and BMI Influence on Copper, Zinc, and Their Major Serum Carrier Proteins in a Large European Population Including Nonagenarian Offspring From MARK-AGE Study
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Piacenza, Francesco, primary, Giacconi, Robertina, additional, Costarelli, Laura, additional, Basso, Andrea, additional, Bürkle, Alexander, additional, Moreno-Villanueva, María, additional, Dollé, Martijn E T, additional, Jansen, Eugène, additional, Grune, Tilman, additional, Weber, Daniela, additional, Stuetz, Wolfgang, additional, Gonos, Efstathios S, additional, Schön, Christiane, additional, Bernhardt, Jürgen, additional, Grubeck-Loebenstein, Beatrix, additional, Sikora, Ewa, additional, Toussaint, Olivier, additional, Debacq-Chainiaux, Florence, additional, Franceschi, Claudio, additional, Capri, Miriam, additional, Hervonen, Antti, additional, Hurme, Mikko, additional, Slagboom, Eline, additional, Breusing, Nicolle, additional, Mocchegiani, Eugenio, additional, and Malavolta, Marco, additional
- Published
- 2021
- Full Text
- View/download PDF
39. C-reactive protein and glucose regulation in familial longevity
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Rozing, Maarten P., Mooijaart, Simon P., Beekman, Marian, Wijsman, Carolien A., Maier, Andrea B., Bartke, Andrzej, Westendorp, Rudi G.J., Slagboom, Eline P., and van Heemst, Diana
- Published
- 2011
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- View/download PDF
40. A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the cohorts for heart and aging research in genomic epidemiology consortium
- Author
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Newman, Anne B., Walter, Stefan, Lunetta, Kathryn L., Garcia, Melissa E., Slagboom, Eline, Christensen, Kaare, Arnold, Alice M., Aspelund, Thor, Aulchenko, Yurii S., Benjamin, Emelia J., Christiansen, Lene, D'Agostino, Ralph B., Sr., Fitzpatrick, Annette L., Franceschini, Nora, Glazer, Nicole L., Gudnason, Vilmundur, Hofman, Albert, Kaplan, Robert, Karasik, David, Kelly-Hayes, Margaret, Kiel, Douglas E., Launer, Lenore J., Marciante, Kristin D., Massaro, Joseph M., Miljkovic, Iva, Nalls, Michael A., Hernandez, Dena, Psaty, Bruce M., Rivadeneira, Fernando, Rotter, Jerome, Seshadri, Sudha, Smith, Albert V., Taylor, Kent D., Tiemeier, Henning, Uh, Hae-Won, Uitterlinden, Andre G., Vaupel, James W., Walston, Jeremy, Westendorp, Rudi G.J., Harris, Tamara B., Lumley, Thomas, van Duijn, Cornelia M., and Murabito, Joanne M.
- Subjects
Genomics -- Research ,Single nucleotide polymorphisms -- Research ,Longevity -- Health aspects ,Longevity -- Genetic aspects ,Health ,Seniors - Abstract
Background. Genome-wide association studies (GWAS) may yield insights into longevity. Methods. We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/ Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. Results. There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x [10.sup.-8]. Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x [10.sup.-7] for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage. Conclusion. Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings. Key Words: Longevity--Genome-wide association study--Meta-analysis. doi: 10.1093/gerona/glq028
- Published
- 2010
41. Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies
- Author
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Rodriguez-Fontenla, Cristina, Calaza, Manuel, Evangelou, Evangelos, Valdes, Ana M., Arden, Nigel, Blanco, Francisco J., Carr, Andrew, Chapman, Kay, Deloukas, Panos, Doherty, Michael, Esko, Tõnu, Garcés Aletá, Carlos M., Gomez-Reino Carnota, Juan J., Helgadottir, Hafdis, Hofman, Albert, Jonsdottir, Ingileif, Kerkhof, Hanneke J. M., Kloppenburg, Margreet, McCaskie, Andrew, Ntzani, Evangelia E., Ollier, William E. R., Oreiro, Natividad, Panoutsopoulou, Kalliope, Ralston, Stuart H., Ramos, Yolande F., Riancho, Jose A., Rivadeneira, Fernando, Slagboom, Eline P., Styrkarsdottir, Unnur, Thorsteinsdottir, Unnur, Thorleifsson, Gudmar, Tsezou, Aspasia, Uitterlinden, André G., Wallis, Gillian A., Wilkinson, Mark J., Zhai, Guangju, Zhu, Yanyan, Felson, David T., Ioannidis, John P. A., Loughlin, John, Metspalu, Andres, Meulenbelt, Ingrid, Stefansson, Kari, van Meurs, Joyce B., Zeggini, Eleftheria, Spector, Timothy D., and Gonzalez, Antonio
- Published
- 2014
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42. Association study of the estrogen receptor I gene (ESR1) in anorexia nervosa and eating disorders: No replication found
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Slof-Op ʼt Landt, Margarita C.T., van Furth, Eric F., Meulenbelt, Ingrid, Bartels, Meike, Hottenga, Jouke Jan, Slagboom, Eline P., and Boomsma, Dorret I.
- Published
- 2014
- Full Text
- View/download PDF
43. Renal function in familial longevity: the Leiden Longevity Study
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de Goeij, Moniek C.M., Halbesma, Nynke, Dekker, Friedo W., Wijsman, Carolien A., van Heemst, Diana, Maier, Andrea B., Mooijaart, Simon P., Slagboom, Eline P., Westendorp, Rudi G.J., and de Craen, Anton J.M.
- Published
- 2014
- Full Text
- View/download PDF
44. Preserved white matter integrity is a marker of familial longevity
- Author
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Altmann-Schneider, Irmhild, de Craen, Anton J. M., Veer, Ilya M., van den Berg-Huysmans, Annette A., Slagboom, Eline P., Westendorp, Rudi G. J., van Buchem, Mark A., and van der Grond, Jeroen
- Published
- 2013
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- View/download PDF
45. Systematic evaluation of normalization methods for glycomics data based on performance of network inference
- Author
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Benedetti, Elisa, Gerstner, Nathalie, Pučić-Baković, Maja, Keser, Toma, Reiding, Karli R, Ruhaak, L Renee, Štambuk, Tamara, Selman, Maurice H J, Rudan, Igor, Polašek, Ozren, Hayward, Caroline, Beekman, Marian, Slagboom, Eline, Wuhrer, Manfred, Dunlop, Malcolm G, Lauc, Gordan, Krumsiek, Jan, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Afd Biomol.Mass Spect. and Proteomics, and Biomolecular Mass Spectrometry and Proteomics
- Subjects
0301 basic medicine ,Normalization (statistics) ,Computer science ,Endocrinology, Diabetes and Metabolism ,Gaussian ,lcsh:QR1-502 ,Inference ,gaussian graphical models ,computer.software_genre ,Mass spectrometry ,01 natural sciences ,Biochemistry ,lcsh:Microbiology ,Article ,glycomics ,Database normalization ,Glycomics ,010104 statistics & probability ,03 medical and health sciences ,symbols.namesake ,Graphical model ,0101 mathematics ,Molecular Biology ,Data Normalization ,Gaussian Graphical Models ,030304 developmental biology ,0303 health sciences ,data normalization ,business.industry ,Probabilistic logic ,Pattern recognition ,3. Good health ,Matrix-assisted laser desorption/ionization ,030104 developmental biology ,symbols ,Data mining ,Artificial intelligence ,business ,computer - Abstract
Glycomics measurements, like all other high-throughput technologies, are subject to technical variation due to fluctuations in the experimental conditions. The removal of this non-biological signal from the data is referred to as normalization. Contrary to other omics data types, a systematic evaluation of normalization options for glycomics data has not been published so far. In this paper, we assess the quality of different normalization strategies for glycomics data with an innovative approach. It has been shown previously that Gaussian Graphical Models (GGMs) inferred from glycomics data are able to identify enzymatic steps in the glycan synthesis pathways in a data-driven fashion. Based on this finding, here, we quantify the quality of a given normalization method according to how well a GGM inferred from the respective normalized data reconstructs known synthesis reactions in the glycosylation pathway. The method therefore exploits a biological measure of goodness. We analyzed 23 different normalization combinations applied to six large-scale glycomics cohorts across three experimental platforms: Liquid Chromatography &ndash, ElectroSpray Ionization - Mass Spectrometry (LC-ESI-MS), Ultra High Performance Liquid Chromatography with Fluorescence Detection (UHPLC-FLD), and Matrix Assisted Laser Desorption Ionization &ndash, Furier Transform Ion Cyclotron Resonance &ndash, Mass Spectrometry (MALDI-FTICR-MS). Based on our results, we recommend normalizing glycan data using the &lsquo, Probabilistic Quotient&rsquo, method followed by log-transformation, irrespective of the measurement platform. This recommendation is further supported by an additional analysis, where we ranked normalization methods based on their statistical associations with age, a factor known to associate with glycomics measurements.
- Published
- 2020
46. Interleukin-6 Signaling Effects on Ischemic Stroke and Other Cardiovascular Outcomes: A Mendelian Randomization Study
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Georgakis, Marios K, Malik, Rainer, Gordon, William, Davey-Smith, George, Morrison, Alanna C, Hicks, Andrew, van Duijn, Cornelia M, Ward-Caviness, Cavin, Boerwinkle, Eric, Rotter, J., Rice, Ken, Lange, Leslie, Perola, Markus, van Hylckama Vlieg, Astrid, de Geus, Eco, Morris, Andrew P, Makela, Kari Matti, Stacey, David, Eriksson, Johan, Frayling, Tim M, Slagboom, Eline P, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Chen, Ming-Huei, Gill, Dipender, Turman, Constance, Germain, Marine, Wiggins, Kerri L, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Franceschini, Nora, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Damrauer, Scott M, Natarajan, Pradeep, Klarin, Derek, de Vries, Paul S, SabaterLleal, Maria, Huffman, Jennifer E, Bammler, Theo K, Sudlow, Cathie L M, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-François, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Dichgans, Martin, Kraft, Peter, Hansen, JohnBjarne, Rosendaal, Frits R, Heit, John A, Psaty, Bruce M, Tang, Weihong, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre Emmanuel, INVENT Consortium, CHARGE Inflammation Working Group, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David-Alexandre, Smith, Nicholas L, Benjamin, Emelia, Dehghan, Abbas, Ahluwalia, Tarunveer Singh, Meigs, James, Tracy, Russell, Lindstrom, Sara, Alizadeh, Behrooz Z, Ligthart, Symen, Bis, Josh, Eiriksdottir, Gudny, Gross, Myron, Rainer, Alex, Snieder, Harold, Wilson, James G, Wang, Lu, Dupuis, Josee, Prins, Bram, Vaso, Urmo, Stathopoulou, Maria, Franke, Lude, Lehtimaki, Terho, Koenig, Wolfgang, Jamshidi, Yalda, Siest, Sophie, Abbasi, Ali, Smith, Erin N, Uitterlinden, Andre G, Abdollahi, Mohammadreza, Schnabel, Renate, Schick, Ursula M, Nolte, Ilja M, Kraja, Aldi, Hsu, Yi-Hsiang, Tylee, Daniel S, Zwicker, Alyson, Uher, Rudolf, Environmental Geography (former), and Biological Psychology
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Male ,Genome-wide association study ,Disease ,030204 cardiovascular system & hematology ,Coronary artery disease ,0302 clinical medicine ,Medicine ,genetics ,Myocardial infarction ,Stroke ,diagnostic imaging [Ischemic Stroke] ,0303 health sciences ,Atrial fibrillation ,General Medicine ,stroke ,3. Good health ,Cardiology ,Female ,coronary artery disease ,INVENT Consortium,CHARGE Inflammation Working Group ,Signal Transduction ,medicine.medical_specialty ,genetics [Interleukin-6] ,Lower risk ,genetics [Signal Transduction] ,03 medical and health sciences ,Internal medicine ,Mendelian randomization ,Research Letter ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Ischemic Stroke ,030304 developmental biology ,Interleukin-6 ,business.industry ,Odds ratio ,genetics [Ischemic Stroke] ,Mendelian Randomization Analysis ,medicine.disease ,cardiovascular diseases ,inflammation ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
BackgroundStudies in humans and experimental models highlight a role of interleukin-6 (IL-6) in cardiovascular disease. Indirect evidence suggests that inhibition of IL-6 signaling could lower risk of coronary artery disease. However, whether such an approach would be effective for ischemic stroke and other cardiovascular outcomes remains unknown.MethodsIn a genome-wide association study (GWAS) of 204,402 European individuals, we identified genetic proxies for downregulated IL-6 signaling as genetic variants in the IL-6 receptor (IL6R) locus that were associated with lower C-reactive protein (CRP) levels, a downstream effector of IL-6 signaling. We then applied two-sample Mendelian randomization (MR) to explore associations with ischemic stroke and its major subtypes (large artery stroke, cardioembolic stroke, small vessel stroke) in the MEGASTROKE dataset (34,217 cases and 404,630 controls), with coronary artery disease in the CARDIoGRAMplusC4D dataset (60,801 cases and 123,504 control), and with other cardiovascular outcomes in the UK Biobank (up to 321,406 individuals) and in phenotype-specific GWAS datasets. All effect estimates were scaled to the CRP-decreasing effects of tocilizumab, a monoclonal antibody targeting IL-6R.ResultsWe identified 7 genetic variants as proxies for downregulated IL-6 signaling, which showed effects on upstream regulators (IL-6 and soluble IL-6R levels) and downstream effectors (CRP and fibrinogen levels) of the pathway that were consistent with pharmacological blockade of IL-6R. In MR, proxies for downregulated IL-6 signaling were associated with lower risk of ischemic stroke (Odds Ratio [OR]: 0.89, 95%CI: 0.82-0.97) and coronary artery disease (OR: 0.84, 95%CI: 0.77-0.90). Focusing on ischemic stroke subtypes, we found significant associations with risk of large artery (OR: 0.76, 95%CI: 0.62-0.93) and small vessel stroke (OR: 0.71, 95%CI: 0.59-0.86), but not cardioembolic stroke (OR: 0.95, 95%CI: 0.74-1.22). Proxies for IL-6 signaling inhibition were further associated with a lower risk of myocardial infarction, aortic aneurysm, atrial fibrillation and carotid plaque.ConclusionsWe provide evidence for a causal effect of IL-6 signaling on ischemic stroke, particularly large artery and small vessel stroke, and a range of other cardiovascular outcomes. IL-6R blockade might represent a valid therapeutic target for lowering cardiovascular risk and should thus be investigated in clinical trials.CLINICAL PERSPECTIVEWhat is newWe identified genetic proxies for downregulated IL-6 signaling that had effects on upstream and downstream regulators of the IL-6 signaling pathway consistent with those of pharmacological IL-6R blockadeGenetically downregulated IL-6 signaling was associated with a lower risk of ischemic stroke, and in particular large artery and small vessel strokeSimilar associations were obtained for a broad range of other cardiovascular outcomesWhat are the clinical implicationsInhibition of IL-6 signaling is a promising therapeutic target for lowering risk of stroke and other cardiovascular outcomes and should be further investigated in clinical trials
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- 2020
47. Correction to:A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity (Acta Neuropathologica, (2019), 138, 2, (237-250), 10.1007/s00401-019-02026-8)
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van der Lee, Sven J., Conway, Olivia J., Jansen, Iris, Carrasquillo, Minerva M., Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R., Stringa, Najada, Chen, Jason A., Zettergren, Anna, Andlauer, Till F.M., Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E., Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J., Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A., Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M., Indakoetxea, Begoña, Collij, Lyduine E., Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W., van Berckel, Bart N.M., Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L., Pastor, Pau, Rodríguez Rodríguez, Eloy, Mead, S., Synofzik, M., van Swieten, J. C., Leber, I., Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B.J., Dobson-Stone, C., Schofield, P. R., Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Binetti, G., Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Blesa, R., Landqvist Waldö, M., Nilsson, K., Nilsson, C., Mackenzie, I. R.A., Hsiung, G. Y.R., Mann, D. M.A., Grafman, J., Morris, C. M., Attems, J., Griffiths, T. D., McKeith, I. G., Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Razquin, C., Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C.M., Uphill, J., Collinge, J., Danek, A., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., van der Zee, J., Van Broeckhoven, C., Cappa, S. F., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Rizzu, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Baker, M., Josephs, K. A., Parisi, J. E., Seeley, W. W., Miller, B. L., Karydas, A. M., Rosen, H., Dopper, E. G.P., Seelaar, H., Logroscino, G., Capozzo, R., Novelli, V., Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H. H., Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A. B., Hardy, J., Momeni, P., Boeve, Bradley F., Petersen, Ronald C., Ferman, Tanis J., van Gerpen, Jay A., Reinders, Marcel J.T., Uitti, Ryan J., Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K., van Schoor, Natasja M., Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K., Ross, Owen A., Dickson, Dennis W., Graff-Radford, Neill R., Knopman, David, Rademakers, Rosa, Lemstra, Afina W., Pijnenburg, Yolande A.L., Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F., Hemmer, Bernhard, Huisman, Martijn A., Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A., Sørensen, Thorkild I.A., Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, Coppola, G., Varpetian, A., Foroud, T. M., Levey, A. I., Kukull, W. A., Mendez, M. F., Ringman, J., Chui, H., Cotman, C., DeCarli, C., Geschwind, D. H., Clarimón, Jordi, Christensen, Kaare, Ertekin-Taner, Nilüfer, Scholz, Sonja W., Ramirez, Alfredo, Ruiz, Agustín, Slagboom, Eline, van der Flier, Wiesje M., and Holstege, Henne
- Abstract
The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.
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- 2020
48. Broad phenotype of cysteine-altering
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Rutten, Julie W., Hack, Remco J., Duering, Marco, Gravesteijn, Gido, Dauwerse, Johannes G., Overzier, Maurice, van den Akker, Erik B., Slagboom, Eline, Holstege, Henne, Nho, Kwangsik, Saykin, Andrew, Dichgans, Martin, Malik, Rainer, and Lesnik Oberstein, Saskia A.J.
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Adult ,Male ,Genotype ,CADASIL ,Neuroimaging ,Penetrance ,Article ,Ethnicity ,Humans ,Cysteine ,Registries ,Receptor, Notch3 ,Aged ,Biological Specimen Banks ,Netherlands ,Aged, 80 and over ,Age Factors ,Brain ,Middle Aged ,Magnetic Resonance Imaging ,White Matter ,United Kingdom ,Case-Control Studies ,Mutation ,Female - Abstract
Objective To determine the small vessel disease spectrum associated with cysteine-altering NOTCH3 variants in community-dwelling individuals by analyzing the clinical and neuroimaging features of UK Biobank participants harboring such variants. Methods The exome and genome sequencing datasets of the UK Biobank (n = 50,000) and cohorts of cognitively healthy elderly (n = 751) were queried for cysteine-altering NOTCH3 variants. Brain MRIs of individuals harboring such variants were scored according to Standards for Reporting Vascular Changes on Neuroimaging criteria, and clinical information was extracted with ICD-10 codes. Clinical and neuroimaging data were compared to age- and sex-matched UK Biobank controls and clinically diagnosed patients from the Dutch cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) registry. Results We identified 108 individuals harboring a cysteine-altering NOTCH3 variant (2.2 of 1,000), of whom 75% have a variant that has previously been reported in CADASIL pedigrees. Almost all variants were located in 1 of the NOTCH3 protein epidermal growth factor–like repeat domains 7 to 34. White matter hyperintensity lesion load was higher in individuals with NOTCH3 variants than in controls (p = 0.006) but lower than in patients with CADASIL with the same variants (p < 0.001). Almost half of the 24 individuals with brain MRI had a Fazekas score of 0 or 1 up to age 70 years. There was no increased risk of stroke. Conclusions Although community-dwelling individuals harboring a cysteine-altering NOTCH3 variant have a higher small vessel disease MRI burden than controls, almost half have no MRI abnormalities up to age 70 years. This shows that NOTCH3 cysteine altering variants are associated with an extremely broad phenotypic spectrum, ranging from CADASIL to nonpenetrance.
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- 2019
49. Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
- Author
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van der Lee, Sven J, Conway, Olivia J, Zettergren, Anna, Christensen, Kaare, Ertekin-Taner, Nilüfer, Scholz, Sonja W, Ramirez, Alfredo, Ruiz, Agustín, Slagboom, Eline, van der Flier, Wiesje M, Holstege, Henne, Mead, S., Synofzik, M., Andlauer, Till F M, van Swieten, J. C., Leber, I., Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Schofield, P. R., Diez-Fairen, Monica, Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Simon-Sanchez, Javier, Binetti, G., Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Blesa, R., Landqvist Waldö, M., Lleó, Alberto, Nilsson, K., Nilsson, C., Mackenzie, I. R. A., Hsiung, G-Y R, Mann, D. M. A., Grafman, J., Morris, C. M., Attems, J., Griffiths, T. D., McKeith, I. G., Zetterberg, Henrik, Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Razquin, C., Ortega-Cubero, S., Alonso, E., Nygaard, Marianne, Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Blauwendraat, Cornelis, Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C. M., Uphill, J., Collinge, J., Danek, A., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., Savage, Jeanne E, van der Zee, J., Van Broeckhoven, C., Cappa, S. F., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Mengel-From, Jonas, Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Jansen, Iris, Moreno-Grau, Sonia, Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Rizzu, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Wagner, Michael, Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Baker, M., Josephs, K. A., Fortea, Juan, Parisi, J. E., Seeley, W. W., Miller, B. L., Karydas, A. M., Rosen, H., Dopper, E. G. P., Seelaar, H., Logroscino, G., Capozzo, R., Novelli, V., Keogh, Michael J, Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H-H, Graff, C., Pasquier, F., Rollin, A., Blennow, Kaj, Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A. B., Hardy, J., Momeni, P., Coppola, G., Skoog, Ingmar, Varpetian, A., Foroud, T. M., Levey, A. I., Kukull, W. A., Mendez, M. F., Ringman, J., Chui, H., Cotman, C., DeCarli, C., Friese, Manuel A, Geschwind, D. H., Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, Carrasquillo, Minerva M, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Kleineidam, Luca, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart N M, Alcolea, Daniel, Wiendl, Heinz, van den Akker, Erik, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, DESGESCO, EADB, IFGC, IPDGC, RiMod-FTD, Bank, Netherlands Brain, Boeve, Bradley F, Hernández, Isabel, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel J T, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, van Eijk, Kristel R, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Stringa, Najada, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande A L, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Chen, Jason A, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild I A, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, GIFT, and Clarimón, Jordi
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0301 basic medicine ,Dementia with Lewy bodies ,Disease ,Bioinformatics ,Neurodegenerative disease ,0302 clinical medicine ,Missense mutation ,media_common ,2. Zero hunger ,Longevity ,Brain ,Parkinson Disease ,Phospholipase C Gamma 2 ,Biobank ,3. Good health ,ddc ,Frontotemporal Dementia ,Microglia ,Alzheimer's disease ,Alzheimer’s disease ,Amyotrophic lateral sclerosis ,Frontotemporal dementia ,Multiple sclerosis ,PLCG2 ,Parkinson’s disease ,Progressive supranuclear palsy ,Lewy Body Disease ,Risk ,Multiple Sclerosis ,media_common.quotation_subject ,education ,Neuroimaging ,Genomics ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,SDG 3 - Good Health and Well-being ,Alzheimer Disease ,medicine ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Alleles ,Phospholipase C gamma ,business.industry ,Amyotrophic Lateral Sclerosis ,Correction ,medicine.disease ,030104 developmental biology ,Mutation ,Dementia ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target. The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.
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- 2019
50. Twin studies of metabolomics traits and metabo-phenotype associations
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Boomsma, Dorret, René Pool, Hagenbeek, Fiona, Hankemeier, Thomas, Kluft, Cornelis, Fanos, Vassilios, Nivard, Michel, Bartels, Meike, Harms, Amy, Slagboom, Eline, Biological Psychology, APH - Mental Health, APH - Methodology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, and Amsterdam Reproduction & Development
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Netherlands Twin Register (NTR) - Published
- 2019
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