Search

Your search keyword '"Anette Kalnapenkis"' showing total 4 results
Start Over Author "Anette Kalnapenkis" Topic 0302 clinical medicine
4 results on '"Anette Kalnapenkis"'

1. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression

Author

Mahmoud Elansary, Knut Krohn, Eleonora Porcu, Julia Dmitrieva, Michel Georges, Harm-Jan Westra, Isabel Alves, Matthias Nauck, Jan H. Veldink, Joost Verlouw, Anette Kalnapenkis, Silva Kasela, Alex W. Hewitt, Roy Oelen, Willem H. Ouwehand, Frank Beutner, Ilkka Seppälä, Yukihide Momozawa, Samuli Ripatti, Brenda W.J.H. Penninx, Patrick Deelen, Michael Stumvoll, Jenny van Dongen, Jonathan K. Pritchard, Roman Kreuzhuber, Marie-Julie Favé, Bernett Lee, Hailang Mei, Biao Zeng, Philip Awadalla, Shuang Li, Kate Downes, Gibran Hemani, Urko M. Marigorta, Anke Tönjes, Morris Swertz, Robert Warmerdam, Joseph E. Powell, Mika Kähönen, Urmo Võsa, Brandon L. Pierce, Benjamin P. Fairfax, Anand Kumar Andiappan, Bastiaan T. Heijmans, Martina Müller-Nurasyid, Sven Bergmann, Katharina Schramm, Hanieh Yaghootkar, Sina Rüeger, Monique G. P. van der Wijst, Lude Franke, Ting Qi, Rick Jansen, Greg Gibson, Cisca Wijmenga, Marc Jan Bonder, Yungil Kim, Viktorija Kukushkina, Johannes Kettunen, Joachim Thiery, Peter A C 't Hoen, Zoltán Kutalik, Jian Yang, Dylan H. de Vries, Olaf Rötzschke, Maarten van Iterson, Peter Kovacs, Peter M. Visscher, Wibowo Arindrarto, Oliver Stegle, Natalia Pervjakova, Julian C. Knight, Tõnu Esko, Annique Claringbould, Lili Milani, Patrick F. Sullivan, Habibul Ahsan, Timothy M. Frayling, Lin Tong, Uwe Völker, Reyhan Sönmez Flitman, Eline Slagboom, Dorret I. Boomsma, Holger Prokisch, Michel G. Nivard, Mawusse Agbessi, Joyce B. J. van Meurs, Alexis Battle, Futao Zhang, Emmanouil T. Dermitzakis, Morris A. Swertz, Grant W. Montgomery, Terho Lehtimäki, Coen D.A. Stehouwer, Jaanika Kronberg, Holger Kirsten, Olli T. Raitakari, Sina A. Gharib, Bruce M. Psaty, Seyhan Yazar, Markus Loeffler, Harm Brugge, Jose Alquicira Hernandez, Mark W. Christiansen, Andrew A. Brown, Markus Perola, Markus Scholz, Ashis Saha, Alexander Teumer, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), BIOS Consortium, i2QTL Consortium, 't Hoen, PAC, van Meurs, J., van Dongen, J., van Iterson, M., Swertz, M.A., Jan Bonder, M., Biological Psychology, APH - Personalized Medicine, APH - Methodology, Internal Medicine, Interne Geneeskunde, MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), and RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome

Subjects
DISORDER, Multifactorial Inheritance, Quantitative Trait Loci, Genome-wide association study, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Gene Expression Regulation/genetics, DISEASE, LINKS, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, RELEVANCE, Blood Proteins/genetics, Gene expression, Genetics, Humans, GENOME-WIDE ASSOCIATION, Polymorphism, Gene, Multifactorial Inheritance/genetics, 030304 developmental biology, Regulation of gene expression, RISK, 0303 health sciences, ARCHITECTURE, Blood Proteins, Transcriptome/genetics, Polymorphism, Single Nucleotide/genetics, Phenotype, SERINE BIOSYNTHESIS, HUMAN TRANSCRIPTOME, DEFICIENCY, Gene Expression Regulation, Expression quantitative trait loci, genome-wide association studies, gene expression, gene regulation, Quantitative Trait Loci/genetics, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Single Nucleotide/genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes.Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

Published
2021
Full Text
View/download PDF

2. Refining Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Genetic Loci by Integrating Summary Data From Genome-wide Association, Gene Expression, and DNA Methylation Studies

Author

Anke R. Hammerschlag, Enda M. Byrne, Meike Bartels, Naomi R. Wray, Christel M. Middeldorp, Mawussé Agbessi, Habibul Ahsan, Isabel Alves, Anand Andiappan, Wibowo Arindrarto, Philip Awadalla, Alexis Battle, Frank Beutner, Marc Jan Bonder, Dorret I. Boomsma, Mark Christiansen, Annique Claringbould, Patrick Deelen, Tõnu Esko, Marie-Julie Favé, Lude Franke, Timothy Frayling, Sina A. Gharib, Gregory Gibson, Bastiaan T. Heijmans, Gibran Hemani, Rick Jansen, Mika Kähönen, Anette Kalnapenkis, Silva Kasela, Johannes Kettunen, Yungil Kim, Holger Kirsten, Peter Kovacs, Knut Krohn, Jaanika Kronberg-Guzman, Viktorija Kukushkina, Zoltan Kutalik, Bernett Lee, Terho Lehtimäki, Markus Loeffler, Urko M. Marigorta, Hailang Mei, Lili Milani, Grant W. Montgomery, Martina Müller-Nurasyid, Matthias Nauck, Michel Nivard, Brenda Penninx, Markus Perola, Natalia Pervjakova, Brandon L. Pierce, Joseph Powell, Holger Prokisch, Bruce M. Psaty, Olli T. Raitakari, Samuli Ripatti, Olaf Rotzschke, Sina Rüeger, Ashis Saha, Markus Scholz, Katharina Schramm, Ilkka Seppälä, Eline P. Slagboom, Coen D.A. Stehouwer, Michael Stumvoll, Patrick Sullivan, Peter A.C. ‘t Hoen, Alexander Teumer, Joachim Thiery, Lin Tong, Anke Tönjes, Jenny van Dongen, Maarten van Iterson, Joyce van Meurs, Jan H. Veldink, Joost Verlouw, Peter M. Visscher, Uwe Völker, Urmo Võsa, Harm-Jan Westra, Cisca Wijmenga, Hanieh Yaghootkar, Jian Yang, Biao Zeng, Futao Zhang, Aaron Isaacs, René Pool, Jouke J. Hottenga, Marleen MJ. van Greevenbroek, Carla J.H. van der Kallen, Casper G. Schalkwijk, Sasha Zhernakova, Ettje F. Tigchelaar, P. Eline Slagboom, Marian Beekman, Joris Deelen, Diana van Heemst, Leonard H. van den Berg, Cornelia M. van Duijn, Bert A. Hofman, André G. Uitterlinden, P. Mila Jhamai, Michael Verbiest, H.Eka D. Suchiman, Marijn Verkerk, Ruud van der Breggen, Jeroen van Rooij, Nico Lakenberg, Michiel van Galen, Jan Bot, Daria V. Zhernakova, Peter van ‘t Hof, Irene Nooren, Matthijs Moed, Martijn Vermaat, René Luijk, Freerk van Dijk, Szymon M. Kielbasa, Morris A. Swertz, Erik. W. van Zwet, Peter-Bram ‘t Hoen, MUMC+: Centrum voor Chronische Zieken (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, MUMC+: HVC Pieken Maastricht Studie (9), Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), Urology, Medical Informatics, Department of Marketing Management, Epidemiology, Internal Medicine, Dermatology, Ophthalmology, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, VU University medical center, Clinical chemistry, Human genetics, APH - Digital Health, APH - Methodology, Biological Psychology, APH - Personalized Medicine, and APH - Health Behaviors & Chronic Diseases

Subjects
0301 basic medicine, Candidate gene, mQTL, Autism Spectrum Disorder, Gene Expression, Genome-wide association study, Biology, Quantitative trait locus, VARIANTS, eQTL, 03 medical and health sciences, 0302 clinical medicine, Mendelian randomization, mental disorders, Humans, GWAS, BRAIN, Biological Psychiatry, Genetic association, Genetics, Regulation of gene expression, Pleiotropy, HERITABILITY, dNaM, DNA Methylation, SMR, Fetal brain, PREVALENCE, 030104 developmental biology, Attention Deficit Disorder with Hyperactivity, DNA methylation, 17Q21.31, Psychiatric disorders, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

BACKGROUND: Recent genome-wide association studies (GWASs) identified the first genetic loci associated with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The next step is to use these results to increase our understanding of the biological mechanisms involved. Most of the identified variants likely influence gene regulation. The aim of the current study is to shed light on the mechanisms underlying the genetic signals and prioritize genes by integrating GWAS results with gene expression and DNA methylation (DNAm) levels.METHODS: We applied summary-data-based Mendelian randomization to integrate ADHD and ASD GWAS data with fetal brain expression and methylation quantitative trait loci, given the early onset of these disorders. We also analyzed expression and methylation quantitative trait loci datasets of adult brain and blood, as these provide increased statistical power. We subsequently used summary-data-based Mendelian randomization to investigate if the same variant influences both DNAm and gene expression levels.RESULTS: We identified multiple gene expression and DNAm levels in fetal brain at chromosomes 1 and 17 that were associated with ADHD and ASD, respectively, through pleiotropy at shared genetic variants. The analyses in brain and blood showed additional associated gene expression and DNAm levels at the same and additional loci, likely because of increased statistical power. Several of the associated genes have not been identified in ADHD and ASD GWASs before.CONCLUSIONS: Our findings identified the genetic variants associated with ADHD and ASD that likely act through gene regulation. This facilitates prioritization of candidate genes for functional follow-up studies.

Published
2020
Full Text
View/download PDF

3. Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals

Author

Tom Palmer, Lars Lind, George Davey Smith, Ting Qi, Michael W. Nagle, Paul W. Franks, Bram P. Prins, Julie Lee, Jingyuan Fu, Niclas Eriksson, Peter K. Joshi, Chris Haley, Ljubica Perisic Matic, Jeremy D. Gale, Mika Ala-Korpela, Michael V. Holmes, Urmo Võsa, Adam S. Butterworth, Eric B. Fauman, Anette Kalnapenkis, Reedik Mägi, Åsa Johansson, James F. Wilson, Mikael Landén, Gunnar Engström, Johan Ärnlöv, Anders Hamsten, Ozren Polasek, Andres Ingason, Andrew J. Schork, Agneta Siegbahn, Lasse Folkersen, Qin Wang, Andrew P. Morris, Johan Sundström, Daria V. Zhernakova, Olle Melander, Erik Ingelsson, Federico De Masi, Lude Franke, James E. Peters, Alexandra Zhernakova, Seung Hoan Choi, Rasmus Wernersson, Thibaud Boutin, Karl Michaëlsson, Stefan Gustafsson, Bianca E. Suur, Karen Page, Yang Wu, Caroline Hayward, Marketa Sjögren, Cecilia M. Lindgren, Stefan Enroth, Tõnu Esko, Amira Quazi, John Danesh, Anders Mälarstig, Daniel Hvidberg Hansen, Åsa K Hedman, Jan Nilsson, Ulf Gyllensten, Vilmantas Giedraitis, J. Gustav Smith, Martin Magnusson, Marju Orho-Melander, Steven A. Lubitz, Erin Macdonald-Dunlop, Thomas Werge, Praveen Surendran, Yan Chen, Céline Fernandez, Weidong Zhang, Lars Wallentin, Andrew D. Bretherick, Jian Yang, Peter M. Nilsson, Jesper R. Gådin, Annique Claringbould, Sölve Elmståhl, Sarah E Bergen, Harm-Jan Westra, Erik Pålsson, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), United Kingdom Research and Innovation, Folkersen, Lasse [0000-0003-0708-9530], Hansen, Daniel Hvidberg [0000-0003-3285-605X], Wu, Yang [0000-0002-0128-7280], Eriksson, Niclas [0000-0002-2152-4343], Bretherick, Andrew D [0000-0001-9258-3140], Enroth, Stefan [0000-0002-5056-9137], Lee, Julie [0000-0001-6090-6718], Ala-Korpela, Mika [0000-0001-5905-1206], Claringbould, Annique [0000-0002-9201-6557], Davey Smith, George [0000-0002-1407-8314], Fauman, Eric [0000-0002-9739-0249], Fernandez, Celine [0000-0003-1290-4982], Franke, Lude [0000-0002-5159-8802], Franks, Paul W [0000-0002-0520-7604], Giedraitis, Vilmantas [0000-0003-3423-2021], Haley, Chris [0000-0002-9811-0210], Johansson, Åsa [0000-0002-2915-4498], Lubitz, Steven [0000-0002-9599-4866], Palmer, Tom [0000-0003-4655-4511], Macdonald-Dunlop, Erin [0000-0001-6569-6086], Magnusson, Martin [0000-0003-1710-5936], Michaelsson, Karl [0000-0003-2815-1217], Nagle, Michael W [0000-0002-4677-7582], Nilsson, Peter M [0000-0002-5652-8459], Nilsson, Jan [0000-0002-9752-7479], Prins, Bram [0000-0001-5774-034X], Sundström, Johan [0000-0003-2247-8454], Werge, Thomas [0000-0003-1829-0766], Westra, Harm-Jan [0000-0001-7038-567X], Fu, Jingyuan [0000-0001-5578-1236], Esko, Tõnu [0000-0003-1982-6569], Hayward, Caroline [0000-0002-9405-9550], Landen, Mikael [0000-0002-4496-6451], Butterworth, Adam S [0000-0002-6915-9015], Holmes, Michael V [0000-0001-6617-0879], Ingelsson, Erik [0000-0003-2256-6972], Mälarstig, Anders [0000-0003-2608-1358], Apollo - University of Cambridge Repository, and 30387078 - Magnusson, P. Martin

Subjects
Proteomics, Proteome, Endocrinology, Diabetes and Metabolism, Asthma, ATP Binding Cassette Transporter 1, Cardiovascular System, Chromosome Mapping, Drug Delivery Systems, Gene Knockdown Techniques, Genome-Wide Association Study, Genomics, Humans, Inflammatory Bowel Diseases, Interleukin-1 Receptor-Like 1 Protein, Intracellular Signaling Peptides and Proteins, Linkage Disequilibrium, Mendelian Randomization Analysis, Protein-Serine-Threonine Kinases, Quantitative Trait Loci, Receptors, CCR2, Receptors, CCR5, Genome-wide association study, 030204 cardiovascular system & hematology, Chemokine receptor, 0302 clinical medicine, RECEPTOR ANTAGONIST, GWAS, Cardiac and Cardiovascular Systems, 0303 health sciences, Molecular medicine, 3. Good health, Medical genetics, Medical Genetics, Life Sciences & Biomedicine, medicine.medical_specialty, Computational biology, Biology, Protein Serine-Threonine Kinases, Article, 03 medical and health sciences, Endocrinology & Metabolism, Physiology (medical), Mendelian randomization, Internal Medicine, medicine, 030304 developmental biology, Science & Technology, Cell Biology, GENE, ANTIBODY
Abstract

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.

Published
2020
Full Text
View/download PDF

4. Unraveling the polygenic architecture of complex traits using blood eQTL metaanalysis

Author

Dmitreva J, van Iterson M, Brenda W.J.H. Penninx, Reyhan Sonmez, Michel Georges, Tõnu Esko, Matthias Nauck, Eline Slagboom, Bruce M. Psaty, Urko M. Marigorta, Michel G. Nivard, C Wijmenga, Markus Perola, Joost Verlouw, Jaanika Kronberg-Guzman, Bastiaan T. Heijmans, van Dongen J, Martina Müller-Nurasyid, Yukihide Momozawa, Silva Kasela, Joseph E. Powell, Sina Rüeger, Brandon L. Pierce, Sven Bergmann, van Meurs J, Lude Franke, Uwe Völker, Futao Zhang, Marc Jan Bonder, Z. Kutalik, Frank Beutner, Ilkka Seppälä, Jarno Kettunen, Morris A. Swertz, Harm-Jan Westra, Jan H. Veldink, Hailiang Mei, Joachim Thiery, Jian Yang, Anand Kumar Andiappan, Grant W. Montgomery, Wibowo Arindrarto, Julian C. Knight, Markus Scholz, Mark W. Christiansen, Alexander Teumer, Bernett Lee, Patrick Deelen, Willem H. Ouwehand, Roman Kreuzhuber, Ashis Saha, Andrew A. Brown, Marie-Julie Favé, Eleonora Porcu, Mawusse Agbessi, Samuli Ripatti, Terho Lehtimäki, Jonathan K. Pritchard, Lili Milani, Alexis Battle, Holger Kirsten, Sina A. Gharib, Natalia Pervjakova, Annique Claringbould, Patrick F. Sullivan, Habibul Ahsan, Katharina Schramm, Hanieh Yaghootkar, Oliver Stegle, D.I. Boomsma, Anette Kalnapenkis, Mika Kähönen, Harm Brugge, Lin Tong, Biao Zeng, Holger Prokisch, Kate Downes, Rick Jansen, Peter M. Visscher, Benjamin P. Fairfax, Shuang Li, Urmo Võsa, Emmanouil T. Dermitzakis, Michael Stumvoll, Markus Loeffler, Alvaes I, Rotzchke O, Philip Awadalla, Coen D.A. Stehouwer, Olli T. Raitakari, Gibran Hemani, Peter Kovacs, Peter A C 't Hoen, Timothy M. Frayling, Anke Tönjes, Greg Gibson, Yungil Kim, Kukushkina, Mahmoud Elansary, and Knut Krohn

Subjects
Genetics, 0303 health sciences, Genome-wide association study, Genomics, Quantitative trait locus, Biology, Genetic architecture, 03 medical and health sciences, 0302 clinical medicine, Expression quantitative trait loci, Trait, Gene, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract

SummaryWhile many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear.To identify these effects, we performedcis-andtrans-expressionquantitative trait locus (eQTL) analysis in blood from 31,684 individuals through the eQTLGen Consortium.We observed thatcis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting our ability to usecis-eQTLs to pinpoint causal genes within susceptibility loci.In contrast, trans-eQTLs (detected for 37% of 10,317 studied trait-associated variants) were more informative. Multiple unlinked variants, associated to the same complex trait, often converged on trans-genes that are known to play central roles in disease etiology.We observed the same when ascertaining the effect of polygenic scores calculated for 1,263 genome-wide association study (GWAS) traits. Expression levels of 13% of the studied genes correlated with polygenic scores, and many resulting genes are known to drive these traits.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results