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2. New insights into the (epi)genetics of twinning.

Author

Dongen, Jenny van, Hubers, Nikki, and Boomsma, Dorret I

Subjects
*GENETICS, *TWINS, *MULTIPLE pregnancy, *DNA methylation
Abstract

Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in families and their prevalence varies widely around the globe. In contrast, monozygotic (MZ) twins occur at a constant rate across time and geographical regions and, with some rare exceptions, do not cluster in families. The leading hypothesis for MZ twins, which arise when a zygote splits during preimplantation stages of development, is random occurrence. We have found the first series of genes underlying the liability of being the mother of DZ twins and have shown that being an MZ twin is strongly associated with a stable DNA methylation signature in child and adult somatic tissues. Because identical twins keep this molecular signature across the lifespan, this discovery opens up completely new possibilities for the retrospective diagnosis of whether a person is an MZ twin whose co-twin may have vanished in the early stages of pregnancy. Here, we summarize the gene finding results for mothers of DZ twins based on genetic association studies followed by meta-analysis, and further present the striking epigenetic results for MZ twins. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Genome-wide association study meta-analysis of dizygotic twinning illuminates genetic regulation of female fecundity.

Author

Mbarek, Hamdi, Gordon, Scott D, Duffy, David L, Hubers, Nikki, Mortlock, Sally, Beck, Jeffrey J, Hottenga, Jouke-Jan, Pool, René, Dolan, Conor V, Actkins, Ky'Era V, Gerring, Zachary F, Dongen, Jenny Van, Ehli, Erik A, Iacono, William G, Mcgue, Matt, Chasman, Daniel I, Gallagher, C Scott, Schilit, Samantha L P, Morton, Cynthia C, and Paré, Guillaume

Subjects
OVULATION, GENETIC regulation, GENOME-wide association studies, TWINS, FERTILITY, LOCUS (Genetics), DISEASE risk factors
Abstract

STUDY QUESTION Which genetic factors regulate female propensity for giving birth to spontaneous dizygotic (DZ) twins? SUMMARY ANSWER We identified four new loci, GNRH1 , FSHR , ZFPM1 , and IPO8 , in addition to previously identified loci, FSHB and SMAD3. WHAT IS KNOWN ALREADY The propensity to give birth to DZ twins runs in families. Earlier, we reported that FSHB and SMAD3 as associated with DZ twinning and female fertility measures. STUDY DESIGN, SIZE, DURATION We conducted a genome-wide association meta-analysis (GWAMA) of mothers of spontaneous dizygotic (DZ) twins (8265 cases, 264 567 controls) and of independent DZ twin offspring (26 252 cases, 417 433 controls). PARTICIPANTS/MATERIALS, SETTING, METHODS Over 700 000 mothers of DZ twins, twin individuals and singletons from large cohorts in Australia/New Zealand, Europe, and the USA were carefully screened to exclude twins born after use of ARTs. Genetic association analyses by cohort were followed by meta-analysis, phenome wide association studies (PheWAS), in silico and in vivo annotations, and Zebrafish functional validation. MAIN RESULTS AND THE ROLE OF CHANCE This study enlarges the sample size considerably from previous efforts, finding four genome-wide significant loci, including two novel signals and a further two novel genes that are implicated by gene level enrichment analyses. The novel loci, GNRH1 and FSHR , have well-established roles in female reproduction whereas ZFPM1 and IPO8 have not previously been implicated in female fertility. We found significant genetic correlations with multiple aspects of female reproduction and body size as well as evidence for significant selection against DZ twinning during human evolution. The 26 top single nucleotide polymorphisms (SNPs) from our GWAMA in European-origin participants weakly predicted the crude twinning rates in 47 non-European populations (r  = 0.23 between risk score and population prevalence, s.e. 0.11, 1-tail P = 0.058) indicating that genome-wide association studies (GWAS) are needed in African and Asian populations to explore the causes of their respectively high and low DZ twinning rates. In vivo functional tests in zebrafish for IPO8 validated its essential role in female, but not male, fertility. In most regions, risk SNPs linked to known expression quantitative trait loci (eQTLs). Top SNPs were associated with in vivo reproductive hormone levels with the top pathways including hormone ligand binding receptors and the ovulation cycle. LARGE SCALE DATA The full DZT GWAS summary statistics will made available after publication through the GWAS catalog (https://www.ebi.ac.uk/gwas/). LIMITATIONS, REASONS FOR CAUTION Our study only included European ancestry cohorts. Inclusion of data from Africa (with the highest twining rate) and Asia (with the lowest rate) would illuminate further the biology of twinning and female fertility. WIDER IMPLICATIONS OF THE FINDINGS About one in 40 babies born in the world is a twin and there is much speculation on why twinning runs in families. We hope our results will inform investigations of ovarian response in new and existing ARTs and the causes of female infertility. STUDY FUNDING/COMPETING INTEREST(S) Support for the Netherlands Twin Register came from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW) grants, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, 911-09-032, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI.NL, 184.021.007), Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB, European Research Council (ERC-230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1) and the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health and Grand Opportunity grants 1RC2 MH089951. The QIMR Berghofer Medical Research Institute (QIMR) study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498, 1050208, 1075175). L.Y. is funded by Australian Research Council (Grant number DE200100425). The Minnesota Center for Twin and Family Research (MCTFR) was supported in part by USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886) and the National Institute on Drug Abuse (DA05147, DA13240, and DA024417). The Women's Genome Health Study (WGHS) was funded by the National Heart, Lung, and Blood Institute (HL043851 and HL080467) and the National Cancer Institute (CA047988 and UM1CA182913), with support for genotyping provided by Amgen. Data collection in the Finnish Twin Registry has been supported by the Wellcome Trust Sanger Institute, the Broad Institute, ENGAGE—European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, AA-09203, AA15416, and K02AA018755) and the Academy of Finland (grants 100499, 205585, 118555, 141054, 264146, 308248, 312073 and 336823 to J. Kaprio). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. For NESDA, funding was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10000-1002), the Center for Medical Systems Biology (CSMB, NVVO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University's Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, ROI D0042157-01A, MH081802, Grand Opportunity grants 1 RC2 Ml-1089951 and IRC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. Work in the Del Bene lab was supported by the Programme Investissements d'Avenir IHU FOReSIGHT (ANR-18-IAHU-01). C.R. was supported by an EU Horizon 2020 Marie Skłodowska-Curie Action fellowship (H2020-MSCA-IF-2014 #661527). H.S. and K.S. are employees of deCODE Genetics/Amgen. The other authors declare no competing financial interests. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Published
2024
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4. DNA methylation in peripheral tissues and Left-handedness

Author

Odintsova, Veronika, primary, Sudermann, Matthew, additional, Hagenbeek, Fiona, additional, Caramaschi, Doretta, additional, Hottenga, Jouke-Jan, additional, Pool, Rene, additional, BIOS, Biobank-based Integrative Omics Study Consortium, additional, Dolan, Conor, additional, Ligthart, Lannie, additional, Beijsterveldt, Catharina van, additional, Willemsen, Gonneke, additional, de Geus, Eco, additional, Beck, Jeffrey, additional, Ehli, Erik, additional, Cuellar-Partida, Gabriel, additional, Evans, David, additional, Medland, Sarah, additional, Relton, Caroline, additional, Boomsma, Dorret, additional, and Dongen, Jenny van, additional

Published
2021
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5. Epigenome-wide association study of left-handedness for different tissues and ages

Author

Odintsova, Veronika, primary, Sudermann, Matthew, additional, Hagenbeek, Fiona, additional, Caramaschi, Doretta, additional, Hottenga, Jouke-Jan, additional, Pool, René, additional, Dolan, Conor, additional, Ligthart, Lannie, additional, Beijsterveldt, Catharina van, additional, Willemsen, Gonneke, additional, de Geus, Eco, additional, Beck, Jeffrey, additional, Ehli, Erik, additional, Cuellar-Partida, Gabriel, additional, Evans, David, additional, Medland, Sarah, additional, Relton, Caroline, additional, Boomsma, Dorret, additional, and Dongen, Jenny van, additional

Published
2021
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6. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

Author

Karlsson Linnér, Richard, Biroli, Pietro, Kong, Edward, Meddens, S. Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Maël, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal N., Trzaskowski, Maciej, Vlaming, Ronald de, Zünd, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia-Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntané, Gerard, Sanchez-Roige, Sandra, Rooij, Frank J. van, Taskesen, Erdogan, Yang, Wu, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., Mccreight, Jennifer C., Mcintyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Metspalu, Andres, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter-Bram t, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Dongen, Jenny van, Meurs, Joyce van, Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Beauchamp, Jonathan P., Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Ahluwalia, Tarunveer S., Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J. van der, de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Most, Peter J. van der, Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate St, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klaus, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Mcmahon, George, Meisinger, Christa, Meitinger, Thomas, Milaneschi, Yusplitri, Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Räikkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Venturini, Cristina, Vinkhuyzen, Anna A. E., Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johannes, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klaus, Bertram, Lars, Bisgaard, Hans, Borecki, Ingrid B, Bültmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., Duijn, Cornelia M. van, Eriksson, Johan G., Franke, Barbara, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, Harst, Pim van der, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., Mcgue, Matt, Pendleton, Neil, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Hofman, Albert, Laibson, David I., Medland, Sarah E., Meyer, Michelle N., Johannesson, Magnus, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., Auton, Adam, Boardman, Jason D., Clark, David W., Conlin, Andrew, Dolan, Conor C., Fischbacher, Urs, Harris, Kathleen Mullan, Hasler, Gregor, Ikram, Mohammad A., Jain, Sonia, Kessler, Ronald C., Kooyman, Maarten, Mackillop, James, Männikkö, Minna, Morcillo-Suarez, Carlos, Mcqueen, Matthew B., Schmidt, Klaus M., Smart, Melissa C., Sutter, Matthias, White, Jon, Wit, Harriet de, Fehr, Ernst, Kumari, Meena, Laibson, David, Navarro, Arcadi, Palmer, Abraham A., Schunk, Daniel, Stein, Murray B., Svento, Rauli, Timmers, Paul R. H. J., Ursano, Robert J., Wagner, Gert G., Adult Psychiatry, APH - Mental Health, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Human genetics, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, 23and Me Research Team, eQTLgen Consortium, International Cannabis Consortium, Economics, Biological Psychology, Complex Trait Genetics, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Tinbergen Institute, 23andme Research Team, Psychiatric Genomics Consortium, Social Science Genetic Association Consortium, Linner Richard Karlsson, Biroli P, Kong Edward, Meddens Fleur W., Wedow Robbee, Fontana Mark Alan, Lebreton Mael, Tino Stephen P., Abdellaoui Abdel, Hammerschlag Anke R., Nivard Michel G., Okbay Aysu, Rietveld Cornelius A., Timshel Pascal N., Trzaskowski Maciej, de Vlaming Ronald, Zund Christian L., Bao Yanchun, Buzdugan Laura, Caplin Ann H., Chen Chia-Yen, Eibich Peter, Fontanillas Pierre, Gonzalez Juan R., Joshi Peter K., Karhunen Ville, Kleinman Aaron, Levin Remy Z., Lill Christina M., Meddens Gerardus A., Muntane Gerard, Sanchez-Roige Sandra, van Rooij Frank J., Taskesen Erdogan, Wu Yang, Zhang Futao, Agee Michelle, Alipanahi Babak, Bell Robert K., Bryc Katarzyna, Elson Sarah L., Furlotte Nicholas A., Huber Karen E., Litterman Nadia K., McCreight Jennifer C., McIntyre Matthew H., Mountain Joanna L., Northover Carrie A. M., Pitts Steven J., Sathirapongsasuti J. Fah, Sazonova Olga V., Shelton Janie F., Shringarpure Suyash, Tian Chao, Tung Joyce Y., Vacic Vladimir, Wilson Catherine H., Agbessi Mawusse, Ahsan Habibul, Alves Isabel, Andiappan Anand, Awadalla Philip, Battle Alexi, Beutner Frank, Bonder Marc Jan, Boomsma Dorret I., Christiansen Mark, Claringbould Annique, Deelen Patrick, Esko Tonu, Fave Marie-Julie, Franke Lude, Frayling Timothy, Gharib Sina A., Gibson Gregory, Heijmans Bastiaan, Hemani Gibran, Jansen Rick, Kahonen Mika, Kalnapenkis Anette, Kasela Silva, Kettunen Johanne, Kim Yungil, Kirsten Holger, Kovacs Peter, Krohn Knut, Kronberg-Guzman Jaanika, Kukushkina Viktorija, Kutalik Zoltan, Lee Bernett, Lehtimaki Terho, Loeffler Marku, Marigorta Urko M., Metspalu Andre, Milani Lili, Montgomery Grant W., Mueller-Nurasyid Martina, Nauck Matthia, Penninx Brenda, Perola Marku, Pervjakova Natalia, Pierce Brandon, Powell Joseph, Prokisch Holger, Psaty Bruce M., Raitakari Olli, Ring Susan, Ripatti Samuli, Rotzchke Olaf, Rueger Sina, Saha Ashi, Scholz Marku, Schramm Katharina, Seppala Ilkka, Stumvoll Michael, Sullivan Patrick, Hoen Peter-Bramt, Teumer Alexander, Thiery Joachim, Tong Lin, Tonjes Anke, van Dongen Jenny, van Meurs Joyce, Verlouw Joost, Visscher Peter M., Voelker Uwe, Vosa Urmo, Westra Harm-Jan, Yaghootkar Hanieh, Yang Jian, Zeng Biao, Lee James J., Pers Tune H., Turley Patrick, Chen Guo-Bo, Emilsson Valur, Oskarsson Sven, Pickrell Joseph K., Thom Kevin, Timshel Pascal, Ahluwalia Tarunveer S., Bacelis Jona, Baumbach Clemen, Bjornsdottir Gyda, Brandsma Johannes H., Concas Maria Pina, Derringer Jaime, Galesloot Tessel E., Girotto Giorgia, Gupta Richa, Hall Leanne M., Harris Sarah E., Hofer Edith, Horikoshi Momoko, Huffman Jennifer E., Kaasik Kadri, Kalafati Ioanna P., Kong Augustine, Lahti Jari, van der Lee Sven J., de Leeuw Christiaan, Lind Penelope A., Lindgren Karl-Oskar, Liu Tian, Mangino Massimo, Marten Jonathan, Mihailov Evelin, Miller Michael B., van der Most Peter J., Oldmeadow Christopher, Payton Antony, Peyrot Wouter J., Qian Yong, Rueedi Rico, Salvi Erika, Schmidt Boerge, Schraut Katharina E., Shi Jianxin, Smith Albert V., Poot Raymond A., St Pourcain Beate, Thorleifsson Gudmar, Verweij Niek, Vuckovic Dragana, Wellmann Juergen, Yang Jingyun, Zhao Wei, Zhu Zhihong, Alizadeh Behrooz Z., Amin Najaf, Bakshi Andrew, Baumeister Sebastian E., Biino Ginevra, Bonnelykke Klau, Boyle Patricia A., Campbell Harry, Cappuccio Francesco P., Davies Gail, De Neve Jan-Emmanuel, Deloukas Pano, Demuth Ilja, Ding Jun, Eisele Lewin, Eklund Niina, Evans David M., Faul Jessica D., Feitosa Mary F., Forstner Andreas J., Gandin Ilaria, Gunnarsson Bjarni, Halldorsson Bjarni V., Harris Tamara B., Heath Andrew C., Hocking Lynne J., Holliday Elizabeth G., Homuth Georg, Horan Michael A., Hottenga Jouke-Jan, de Jager Philip L., Jugessur Astanand, Kaakinen Marika A., Kanoni Stavroula, Keltigangas-Jarvinen Liisa, Kiemeney Lambertus A. L. M., Kolcic Ivana, Koskinen Seppo, Kraja Aldi T., Kroh Martin, Latvala Antti, Launer Lenore J., Lebreton Mael P., Levinson Douglas F., Lichtenstein Paul, Lichtner Peter, Liewald David C. M., Loukola Anu, Madden Pamela A., Magi Reedik, Maki-Opas Tomi, Marioni Riccardo E., Marques-Vidal Pedro, McMahon George, Meisinger Christa, Meitinger Thoma, Milaneschi Yusplitri, Myhre Ronny, Nelson Christopher P., Nyholt Dale R., Ollier William E. R., Palotie Aarno, Paternoster Lavinia, Pedersen Nancy L., Petrovic Katja E., Porteous David J., Raikkonen Katri, Ring Susan M., Robino Antonietta, Rostapshova Olga, Rudan Igor, Rustichini Aldo, Salomaa Veikko, Sanders Alan R., Sarin Antti-Pekka, Schmidt Helena, Scott Rodney J., Smith Blair H., Smith Jennifer A., Staessen Jan A., Steinhagen-Thiessen Elisabeth, Strauch Konstantin, Terracciano Antonio, Tobin Martin D., Ulivi Sheila, Vaccargiu Simona, Quaye Lydia, Venturini Cristina, Vinkhuyzen Anna A. E., Voelzke Henry, Vonk Judith M., Vozzi Diego, Waage Johanne, Ware Erin B., Willemsen Gonneke, Attia John R., Bennett David A., Berger Klau, Bertram Lar, Bisgaard Han, Borecki Ingrid B., Bultmann Ute, Chabris Christopher F., Cucca Francesco, Cusi Daniele, Deary J., Dedoussis George V., van Duijn Cornelia M., Eriksson Johan G., Franke Barbara, Gasparini Paolo, Gejman Pablo V., Gieger Christian, Grabe Hans-Joergen, Gratten Jacob, Gudnason Vilmundur, van der Harst Pim, Hayward Caroline, Hinds David A., Hoffmann Wolfgang, Hypponen Elina, Iacono William G., Jacobsson Bo, Jarvelin Marjo-Riitta, Jockel Karl-Heinz, Kaprio Jaakko, Kardia Sharon L. R., Lehrer Steven F., Magnusson Patrik K. E., Martin Nicholas G., McGue Matt, Pendleton Neil, Pirastu Nicola, Pirastu Mario, Polasek Ozren, Posthuma Danielle, Power Christine, Province Michael A., Samani Nilesh J., Schlessinger David, Schmidt Reinhold, Sorensen Thorkild I. A., Spector Tim D., Stefansson Kari, Thorsteinsdottir Unnur, Thurik A. Roy, Timpson Nicholas J., Tiemeier Henning, Uitterlinden Andre G., Vitart Veronique, Vollenweider Peter, Weir David R., Wilson James F., Wright Alan F., Conley Dalton C., Krueger Robert F., Smith George Davey, Laibson David I., Medland Sarah E., Johannesson Magnu, Koellinger Philipp D., Cesarini David, Benjamin Daniel J., Auton Adam, Boardman Jason D., Clark David W., Conlin Andrew, Dolan Conor C., Fischbacher Ur, Groenen Patrick J. F., Harris Kathleen Mullan, Hasler Gregor, Hofman Albert, Ikram Mohammad A., Jain Sonia, Karlsson Robert, Kessler Ronald C., Kooyman Maarten, MacKillop Jame, Mannikko Minna, Morcillo-Suarez Carlo, McQueen Matthew B., Schmidt Klaus M., Smart Melissa C., Sutter Matthia, White Jon, de Wit Harriet, Fehr Ernst, Kumari Meena, Laibson David, Meyer Michelle N., Navarro Arcadi, Palmer Abraham A., Schunk Daniel, Stein Murray B., Svento Rauli, Timmers Paul R. H. J., Ursano Robert J., Wagner Gert G., Beauchamp Jonathan P., Karlsson Linnér, Richard, Biroli, Pietro, Kong, Edward, Meddens, S. Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Maël, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal N., Trzaskowski, Maciej, Vlaming, Ronald de, Zünd, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia-Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntané, Gerard, Sanchez-Roige, Sandra, Rooij, Frank J. van, Taskesen, Erdogan, Wu, Yang, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., Mccreight, Jennifer C., Mcintyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexi, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johanne, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Marku, Marigorta, Urko M., Metspalu, Andre, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthia, Penninx, Brenda, Perola, Marku, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rüeger, Sina, Saha, Ashi, Scholz, Marku, Schramm, Katharina, Seppälä, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter-Bram t, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Dongen, Jenny van, Meurs, Joyce van, Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Beauchamp, Jonathan P., Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Ahluwalia, Tarunveer S., Bacelis, Jona, Baumbach, Clemen, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J. van der, de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Most, Peter J. van der, Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate St, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klau, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Pano, Demuth, Ilja, Ding, Jun, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Mcmahon, George, Meisinger, Christa, Meitinger, Thoma, Milaneschi, Yusplitri, Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Räikkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Venturini, Cristina, Vinkhuyzen, Anna A. E., Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johanne, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klau, Bertram, Lar, Bisgaard, Han, Borecki, Ingrid B, Bültmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., Duijn, Cornelia M. van, Eriksson, Johan G., Franke, Barbara, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, Harst, Pim van der, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., Mcgue, Matt, Pendleton, Neil, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Hofman, Albert, Laibson, David I., Medland, Sarah E., Meyer, Michelle N., Johannesson, Magnu, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., Auton, Adam, Boardman, Jason D., Clark, David W., Conlin, Andrew, Dolan, Conor C., Fischbacher, Ur, Harris, Kathleen Mullan, Hasler, Gregor, Ikram, Mohammad A., Jain, Sonia, Kessler, Ronald C., Kooyman, Maarten, Mackillop, Jame, Männikkö, Minna, Morcillo-Suarez, Carlo, Mcqueen, Matthew B., Schmidt, Klaus M., Smart, Melissa C., Sutter, Matthia, White, Jon, Wit, Harriet de, Fehr, Ernst, Kumari, Meena, Laibson, David, Navarro, Arcadi, Palmer, Abraham A., Schunk, Daniel, Stein, Murray B., Svento, Rauli, Timmers, Paul R. H. J., Ursano, Robert J., Wagner, Gert G., Applied Economics, Hematology, Epidemiology, Urology, Department of Marketing Management, Internal Medicine, Medical Informatics, Cell biology, Erasmus MC other, Molecular Genetics, Econometrics, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, RS: Carim - V02 Hypertension and target organ damage, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Public Health Research (PHR), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Linnér, Richard Karlsson, Biroli , Pietro, Meddens, S Fleur W, and Beauchamp, Jonathan P

Subjects
Netherlands Twin Register (NTR), Male, LD, Medizin, Poison control, Genome-wide association study, DETERMINANTS, Cathie Marsh Institute, PREFERENCES, Q1, Genome-wide association studies, HV, 0302 clinical medicine, Genetics, Behavioral/methods, GWAS, Genetics & Heredity, Genetics, 0303 health sciences, PERSONALITY, Genetic Predisposition to Disease/genetics, Behavior/physiology, Polymorphism, Single Nucleotide/genetics, 3. Good health, Manchester Institute for Collaborative Research on Ageing, Meta-analysis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Genetic Loci/genetics, Behavioural genetics, Genome-Wide Association Study/methods, Medical genetics, Female, Life Sciences & Biomedicine, Single Nucleotide/genetics, medicine.medical_specialty, ResearchInstitutes_Networks_Beacons/MICRA, Genotype, Single-nucleotide polymorphism, Genetics, Behavioral, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, ddc:330, medicine, GENDER-DIFFERENCES, SNP, Humans, Genetic Predisposition to Disease, Polymorphism, behavioural genetics, Behavioral/methods, 030304 developmental biology, Genetic association, Behavior, Science & Technology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Data Science, Case-control study, risk tolerance, GWAS, genetic architechture, Genetic Loci, Case-Control Studies, genome-wide association studies, ResearchInstitutes_Networks_Beacons/cathie_marsh_institute, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance. This research was carried out under the auspices of the Social Science Genetic Association Consortium. The research was also conducted using the UK Biobank Resource under application number 11425. The study was supported by funding from the Ragnar Söderberg Foundation (E9/11 and E42/15); the Swedish Research Council (421-2013-1061); the Jan Wallander and Tom Hedelius Foundation; an ERC Consolidator Grant to Philipp Koellinger (647648 EdGe); the Pershing Square Fund of the Foundations of Human Behavior; the Open Philanthropy Project; the National Institute on Aging, National Institutes of Health through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to the National Bureau of Economic Research and R01-AG042568-02 to the University of Southern California; the government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-152); and the Social Sciences and Humanities Research Council of Canada. We thank the International Cannabis Consortium, the eQTLgen Consortium, and the Psychiatric Genomics Consortium for sharing summary statistics from the GWAS of lifetime cannabis use, eQTL summary statistics, and summary statistics from the GWAS of ADHD, respectively. A full list of acknowledgments is provided in the Supplementary Note.

Published
2019
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7. Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Author

Hagenbeek, Fiona A., Pool, Rene, Dongen, Jenny van, Draisma, Harmen H.M., Hottenga, J.J., Willemsen, Gonneke, Boersma, E., Netea, M.G., Deelen, J., Reinders, M.J.T., Hagenbeek, Fiona A., Pool, Rene, Dongen, Jenny van, Draisma, Harmen H.M., Hottenga, J.J., Willemsen, Gonneke, Boersma, E., Netea, M.G., Deelen, J., and Reinders, M.J.T.

Abstract

Contains fulltext : 216654.pdf (publisher's version ) (Open Access)

Published
2020

8. Genetics and Not Shared Environment Explains Familial Resemblance in Adult Metabolomics Data

Author

Pool, Rene, Hagenbeek, Fiona A., Hendriks, Anne M., Dongen, Jenny van, Willemsen, Gonneke, Geus, Eco de, Netea, M.G., Duijn, C.M. van, Slagboom, P.E., Pool, Rene, Hagenbeek, Fiona A., Hendriks, Anne M., Dongen, Jenny van, Willemsen, Gonneke, Geus, Eco de, Netea, M.G., Duijn, C.M. van, and Slagboom, P.E.

Abstract

Contains fulltext : 221504.pdf (Publisher’s version ) (Open Access)

Published
2020

9. Evaluation of commonly used analysis strategies for epigenome- and transcriptome-wide association studies through replication of large-scale population studies

Author

Rooij, Jeroen van, Mandaviya, Pooja R., Claringbould, Annique, Felix, Janine F., Dongen, Jenny van, Jansen, Rick, Hoen, P.A.C. 't, Heijmans, Bas, Meurs, Joyce B.J. van, Rooij, Jeroen van, Mandaviya, Pooja R., Claringbould, Annique, Felix, Janine F., Dongen, Jenny van, Jansen, Rick, Hoen, P.A.C. 't, Heijmans, Bas, and Meurs, Joyce B.J. van

Abstract

Contains fulltext : 212662.pdf (publisher's version ) (Open Access)

Published
2019

10. MOESM3 of Genome-wide analysis of DNA methylation in buccal cells: a study of monozygotic twins and mQTLs

Author

Dongen, Jenny Van, Ehli, Erik, Jansen, Rick, Beijsterveldt, Catharina Van, Willemsen, Gonneke, Hottenga, Jouke, Kallsen, Noah, Peyton, Shanna, Breeze, Charles, Kluft, Cornelis, Heijmans, Bastiaan, Bartels, Meike, Davies, Gareth, and Dorret Boomsma

Abstract

Additional file 3. DHS enrichment for methylation sites with large MZ twin correlation, adjusted for cellular composition.

Published
2018
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11. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

Author

Jia, Tianye, primary, Chu, Congying, additional, Liu, Yun, additional, Dongen, Jenny van, additional, Armstrong, Nicola J, additional, Bastin, Mark E., additional, Carrillo-Roa, Tania, additional, Braber, Anouk den, additional, Harris, Mathew, additional, Jansen, Rick, additional, Liu, Jingyu, additional, Luciano, Michelle, additional, Ori, Anil P.S., additional, Santiañez, Roberto Roiz, additional, Ruggeri, Barbara, additional, Sarkisyan, Daniil, additional, Shin, Jean, additional, Sungeun, Kim, additional, Gutiérrez, Diana Tordesillas, additional, Ent, Dennis van’t, additional, Ames, David, additional, Artiges, Eric, additional, Bakalkin, Georgy, additional, Banaschewski, Tobias, additional, Bokde, Arun L.W., additional, Brodaty, Henry, additional, Bromberg, Uli, additional, Brouwer, Rachel, additional, Büchel, Christian, additional, Quinlan, Erin Burke, additional, Cahn, Wiepke, additional, de Zubicaray, Greig I., additional, Ekström, Tomas J., additional, Flor, Herta, additional, Fröhner, Juliane H., additional, Frouin, Vincent, additional, Garavan, Hugh, additional, Gowland, Penny, additional, Heinz, Andreas, additional, Ittermann, Bernd, additional, Jahanshad, Neda, additional, Jiang, Jiyang, additional, Kwok, John B., additional, Martin, Nicholas G., additional, Martinot, Jean-Luc, additional, Mather, Karen A., additional, McMahon, Katie L., additional, McRae, Allan F., additional, Nees, Frauke, additional, Orfanos, Dimitri Papadopoulos, additional, Paus, Tomáš, additional, Poustka, Luise, additional, Sämann, Philipp G., additional, Schofield, Peter R., additional, Smolka, Michael N., additional, Strike, Lachlan T., additional, Teeuw, Jalmar, additional, Thalamuthu, Anbupalam, additional, Trollor, Julian, additional, Walter, Henrik, additional, Wardlaw, Joanna M., additional, Wen, Wei, additional, Whelan, Robert, additional, Apostolova, Liana G., additional, Binder, Elisabeth B., additional, Boomsma, Dorret I., additional, Calhoun, Vince, additional, Crespo-Facorro, Benedicto, additional, Deary, Ian J., additional, Pol, Hilleke Hulshoff, additional, Ophoff, Roel A., additional, Pausova, Zdenka, additional, Sachdev, Perminder S., additional, Saykin, Andrew, additional, Wright, Margaret J., additional, Thompson, Paul M., additional, Schumann, Gunter, additional, and Desrivières, Sylvane, additional

Published
2018
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12. Additional file 3: Figure S1. of Integrative DNA methylome analysis of pan-cancer biomarkers in cancer discordant monozygotic twin-pairs

Author

Roos, Leonie, Dongen, Jenny Van, Bell, Christopher, Burri, Andrea, Deloukas, Panos, Dorret Boomsma, Spector, Tim, and Bell, Jordana

Abstract

Variability at three top-ranked pan-cancer DMPs in 9 cancer discordant and 480 healthy MZ twin-pairs. Histogram with density overlay of absolute differences of 480 healthy MZ twin-pairs with median (blue) and density and median of differences between 9 cancer discordant MZ twin-pairs (red). At [A] cg0244695 near SASH1, [B] cg26079695 in COL11A2, and [C] cg27094856 in AXL. (PDF 143Â kb)

Published
2016
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13. Additional file 2: Figure S1. of Integrative DNA methylome analysis of pan-cancer biomarkers in cancer discordant monozygotic twin-pairs

Author

Roos, Leonie, Dongen, Jenny Van, Bell, Christopher, Burri, Andrea, Deloukas, Panos, Dorret Boomsma, Spector, Tim, and Bell, Jordana

Abstract

Replication of four top-ranked pan-cancer DMPs in 9 cancer discordant MZ twin-pairs. Direction of association at [A] cg0244695 near SASH1, [B] cg26079695 in COL11A2, [C] cg27094856 in AXL, and [D] cg21046959 in LINC00340. Results are plotted using normalised unadjusted beta values of cancer-affected individuals (left) and healthy individuals (right). The lines connect co-twins in twin-pairs and indicate a consistent direction of effect. (PDF 88Â kb)

Published
2016
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14. Additional file 14: of Blood lipids influence DNA methylation in circulating cells

Author

Dekkers, Koen, Iterson, Maarten Van, Slieker, Roderick, Moed, Matthijs, Bonder, Marc, Galen, Michiel Van, Hailiang Mei, Zhernakova, Daria, Berg, Leonard Van Den, Deelen, Joris, Dongen, Jenny Van, Heemst, Diana Van, Hofman, Albert, Hottenga, Jouke, Kallen, Carla Van Der, Schalkwijk, Casper, Stehouwer, Coen, Tigchelaar, Ettje, AndrĂŠ Uitterlinden, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, Hoen, Peter, Jansen, Rick, Meurs, Joyce Van, Dorret Boomsma, Duijn, Cornelia Van, Greevenbroek, Marleen Van, Veldink, Jan, Wijmenga, Cisca, Zwet, Erik Van, P. Slagboom, J. Jukema, and Heijmans, Bastiaan

Subjects
body regions, nervous system, fungi
Abstract

DNA methylation was associated with gene expression. (PDF 21974Â kb)

Published
2016
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15. Additional file 4: of Blood lipids influence DNA methylation in circulating cells

Author

Dekkers, Koen, Iterson, Maarten Van, Slieker, Roderick, Moed, Matthijs, Bonder, Marc, Galen, Michiel Van, Hailiang Mei, Zhernakova, Daria, Berg, Leonard Van Den, Deelen, Joris, Dongen, Jenny Van, Heemst, Diana Van, Hofman, Albert, Hottenga, Jouke, Kallen, Carla Van Der, Schalkwijk, Casper, Stehouwer, Coen, Tigchelaar, Ettje, AndrĂŠ Uitterlinden, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, Hoen, Peter, Jansen, Rick, Meurs, Joyce Van, Dorret Boomsma, Duijn, Cornelia Van, Greevenbroek, Marleen Van, Veldink, Jan, Wijmenga, Cisca, Zwet, Erik Van, P. Slagboom, J. Jukema, and Heijmans, Bastiaan

Abstract

The EWAS effect size estimates were not sensitive to the exclusion of non-fasted samples, the exclusion of samples with imputed cell counts, or the addition of current smoking behavior, lipid-lowering medication, or BMI as covariates. (PDF 273Â kb)

Published
2016
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16. Additional file 12: of Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms

Author

Slieker, Roderick, Iterson, Maarten Van, RenĂŠ Luijk, Beekman, Marian, Zhernakova, Daria, Moed, Matthijs, Hailiang Mei, Galen, Michiel Van, Deelen, Patrick, Bonder, Marc, Zhernakova, Alexandra, AndrĂŠ Uitterlinden, Tigchelaar, Ettje, Stehouwer, Coen, Schalkwijk, Casper, Kallen, Carla Van Der, Hofman, Albert, Heemst, Diana Van, Eco De Geus, Dongen, Jenny Van, Deelen, Joris, Berg, Leonard Van Den, Meurs, Joyce Van, Jansen, Rick, Hoen, Peter, Franke, Lude, Wijmenga, Cisca, Veldink, Jan, Swertz, Morris, Greevenbroek, Marleen Van, Duijn, Cornelia Van, Dorret Boomsma, P. Slagboom, and Heijmans, Bastiaan

Abstract

Description of external datasets used. (PDF 79 kb)

Published
2016
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17. Additional file 3: of Blood lipids influence DNA methylation in circulating cells

Author

Dekkers, Koen, Iterson, Maarten Van, Slieker, Roderick, Moed, Matthijs, Bonder, Marc, Galen, Michiel Van, Hailiang Mei, Zhernakova, Daria, Berg, Leonard Van Den, Deelen, Joris, Dongen, Jenny Van, Heemst, Diana Van, Hofman, Albert, Hottenga, Jouke, Kallen, Carla Van Der, Schalkwijk, Casper, Stehouwer, Coen, Tigchelaar, Ettje, AndrĂŠ Uitterlinden, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, Hoen, Peter, Jansen, Rick, Meurs, Joyce Van, Dorret Boomsma, Duijn, Cornelia Van, Greevenbroek, Marleen Van, Veldink, Jan, Wijmenga, Cisca, Zwet, Erik Van, P. Slagboom, J. Jukema, and Heijmans, Bastiaan

Subjects
animal structures, embryonic structures, fungi, lipids (amino acids, peptides, and proteins), human activities
Abstract

Estimates and 95Â % confidence intervals for the EWAS-identified CpGs for each cohort contributing to the meta-analysis for TG, LDL-C, and HDL-C. (PDF 297Â kb)

Published
2016
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18. Additional file 2: of Blood lipids influence DNA methylation in circulating cells

Author

Dekkers, Koen, Iterson, Maarten Van, Slieker, Roderick, Moed, Matthijs, Bonder, Marc, Galen, Michiel Van, Hailiang Mei, Zhernakova, Daria, Berg, Leonard Van Den, Deelen, Joris, Dongen, Jenny Van, Heemst, Diana Van, Hofman, Albert, Hottenga, Jouke, Kallen, Carla Van Der, Schalkwijk, Casper, Stehouwer, Coen, Tigchelaar, Ettje, Uitterlinden, André, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, Peter ’T Hoen, Jansen, Rick, Meurs, Joyce Van, Dorret Boomsma, Duijn, Cornelia Van, Greevenbroek, Marleen Van, Veldink, Jan, Wijmenga, Cisca, Zwet, Erik Van, P. Slagboom, J. Jukema, and Heijmans, Bastiaan

Abstract

Quantile–quantile plots depicting the associations between TG, LDL-C, and HDL-C and genome-wide DNA methylation when compared with a uniform distribution expected by chance for a uncorrected meta-analysis z-values and b meta-analysis z-values corrected for genome-wide inflation using genomic control (λ = 1.0). (PDF 14800 kb)

Published
2016
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19. Additional file 9: of Blood lipids influence DNA methylation in circulating cells

Author

Dekkers, Koen, Iterson, Maarten Van, Slieker, Roderick, Moed, Matthijs, Bonder, Marc, Galen, Michiel Van, Hailiang Mei, Zhernakova, Daria, Berg, Leonard Van Den, Deelen, Joris, Dongen, Jenny Van, Heemst, Diana Van, Hofman, Albert, Hottenga, Jouke, Kallen, Carla Van Der, Schalkwijk, Casper, Stehouwer, Coen, Tigchelaar, Ettje, AndrĂŠ Uitterlinden, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, Hoen, Peter, Jansen, Rick, Meurs, Joyce Van, Dorret Boomsma, Duijn, Cornelia Van, Greevenbroek, Marleen Van, Veldink, Jan, Wijmenga, Cisca, Zwet, Erik Van, P. Slagboom, J. Jukema, and Heijmans, Bastiaan

Abstract

Comparison between EWAS and MR estimates (with 95Â % confidence intervals). (PDF 109Â kb)

Published
2016
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20. Additional file 1: Figure S1. of Integrative DNA methylome analysis of pan-cancer biomarkers in cancer discordant monozygotic twin-pairs

Author

Roos, Leonie, Dongen, Jenny Van, Bell, Christopher, Burri, Andrea, Deloukas, Panos, Dorret Boomsma, Spector, Tim, and Bell, Jordana

Abstract

Pan-cancer top-ranked results in 41 discordant MZ twin-pairs. Direction of association at [A] cg26079695 in COL11A2, [B] cg27094856 in AXL, and [C] cg21046959 in LINC00340. Results are plotted using normalised unadjusted beta values of cancer-affected individuals (left) and healthy individuals (right). The lines connect co-twins in twin-pairs and indicate a consistent direction of effect. (PDF 78Â kb)

Published
2016
Full Text
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21. Additional file 5: Figure S1. of Integrative DNA methylome analysis of pan-cancer biomarkers in cancer discordant monozygotic twin-pairs

Author

Roos, Leonie, Dongen, Jenny Van, Bell, Christopher, Burri, Andrea, Deloukas, Panos, Dorret Boomsma, Spector, Tim, and Bell, Jordana

Abstract

Differential methylation with respect to age and time of cancer diagnosis. [A] Time to diagnosis compared to age at blood sample collection, the line represent the least squares regression fit. [B] Unadjusted DNA methylation values at cg02444695 (near SASH1) in affected individuals (red) and healthy co-twins (blue), shown with respect to age at blood sample collection (years) with smooth (LOESS) lines fitted for both groups. [Câ F] Unadjusted DNA methylation values in affected individuals (red) and healthy co-twins (blue), shown with respect to time of diagnosis (years) with smooth (LOESS) lines fitted for both groups with blood samples collected 5 to 11Â years before cancer diagnosis. The orange and black vertical lines represent the time of diagnosis and time window of the main study respectively. At [C] cg0244695 near SASH1, [D] cg26079695 in COL11A2, [E] cg27094856 in AXL, and [F] cg21046959 in LINC00340. (PDF 185Â kb)

Published
2016
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22. eFORGE v2.0: updated analysis of cell type-specific signal in epigenomic data.

Author

Breeze, Charles E, Reynolds, Alex P, Dongen, Jenny van, Dunham, Ian, Lazar, John, Neph, Shane, Vierstra, Jeff, Bourque, Guillaume, Teschendorff, Andrew E, Stamatoyannopoulos, John A, and Beck, Stephan

Subjects
CELL analysis, DNA methylation, GENE enhancers, TRANSCRIPTION factors, DNA analysis, HISTONE methylation
Abstract

Summary The Illumina Infinium EPIC BeadChip is a new high-throughput array for DNA methylation analysis, extending the earlier 450k array by over 400 000 new sites. Previously, a method named eFORGE was developed to provide insights into cell type-specific and cell-composition effects for 450k data. Here, we present a significantly updated and improved version of eFORGE that can analyze both EPIC and 450k array data. New features include analysis of chromatin states, transcription factor motifs and DNase I footprints, providing tools for epigenome-wide association study interpretation and epigenome editing. Availability and implementation eFORGE v2.0 is implemented as a web tool available from https://eforge.altiusinstitute.org and https://eforge-tf.altiusinstitute.org/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Published
2019
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23. Additional file 1: of Blood lipids influence DNA methylation in circulating cells

Author

Dekkers, Koen, Iterson, Maarten Van, Slieker, Roderick, Moed, Matthijs, Bonder, Marc, Galen, Michiel Van, Hailiang Mei, Zhernakova, Daria, Berg, Leonard Van Den, Deelen, Joris, Dongen, Jenny Van, Heemst, Diana Van, Hofman, Albert, Hottenga, Jouke, Kallen, Carla Van Der, Schalkwijk, Casper, Stehouwer, Coen, Tigchelaar, Ettje, AndrĂŠ Uitterlinden, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, Hoen, Peter, Jansen, Rick, Meurs, Joyce Van, Dorret Boomsma, Duijn, Cornelia Van, Greevenbroek, Marleen Van, Veldink, Jan, Wijmenga, Cisca, Zwet, Erik Van, P. Slagboom, J. Jukema, and Heijmans, Bastiaan

Subjects
3. Good health
Abstract

Full list of authors of the BIOS Consortium. (PDF 68Â kb)

24. Additional file 1: of Blood lipids influence DNA methylation in circulating cells

Author

Dekkers, Koen, Iterson, Maarten Van, Slieker, Roderick, Moed, Matthijs, Bonder, Marc, Galen, Michiel Van, Hailiang Mei, Zhernakova, Daria, Berg, Leonard Van Den, Deelen, Joris, Dongen, Jenny Van, Heemst, Diana Van, Hofman, Albert, Hottenga, Jouke, Kallen, Carla Van Der, Schalkwijk, Casper, Stehouwer, Coen, Tigchelaar, Ettje, AndrĂŠ Uitterlinden, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, Hoen, Peter, Jansen, Rick, Meurs, Joyce Van, Dorret Boomsma, Duijn, Cornelia Van, Greevenbroek, Marleen Van, Veldink, Jan, Wijmenga, Cisca, Zwet, Erik Van, P. Slagboom, J. Jukema, and Heijmans, Bastiaan

Subjects
3. Good health
Abstract

Full list of authors of the BIOS Consortium. (PDF 68Â kb)

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