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1. Depressive Symptoms and Plasma Markers of Alzheimer's Disease and Neurodegeneration: A Coordinated Meta-Analysis of 8 Cohort Studies

Author

Twait, Emma L., Kamarioti, Maria, Verberk, Inge M.W., Teunissen, Charlotte E., Nooyens, Astrid C.J., Monique Verschuren, W.M., Visser, Pieter Jelle, Huisman, Martijn, Kok, Almar A.L., Eline Slagboom, P., Beekman, Marian, Vojinovic, Dina, Lakenberg, Nico, Arfan Ikram, M., Schuurmans, Isabel K., Wolters, Frank J., Moonen, Justine E.F., Gerritsen, Lotte, van der Flier, Wiesje M., and Geerlings, Mirjam I.

Published
2024
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2. Depressive Symptoms and Plasma Markers of Alzheimer's Disease and Neurodegeneration:A Coordinated Meta-Analysis of 8 Cohort Studies

Author

Twait, Emma L., Kamarioti, Maria, Verberk, Inge M.W., Teunissen, Charlotte E., Nooyens, Astrid C.J., Monique Verschuren, W. M., Visser, Pieter Jelle, Huisman, Martijn, Kok, Almar A.L., Eline Slagboom, P., Beekman, Marian, Vojinovic, Dina, Lakenberg, Nico, Arfan Ikram, M., Schuurmans, Isabel K., Wolters, Frank J., Moonen, Justine E.F., Gerritsen, Lotte, van der Flier, Wiesje M., Geerlings, Mirjam I., Twait, Emma L., Kamarioti, Maria, Verberk, Inge M.W., Teunissen, Charlotte E., Nooyens, Astrid C.J., Monique Verschuren, W. M., Visser, Pieter Jelle, Huisman, Martijn, Kok, Almar A.L., Eline Slagboom, P., Beekman, Marian, Vojinovic, Dina, Lakenberg, Nico, Arfan Ikram, M., Schuurmans, Isabel K., Wolters, Frank J., Moonen, Justine E.F., Gerritsen, Lotte, van der Flier, Wiesje M., and Geerlings, Mirjam I.

Published
2024

3. Depressive Symptoms and Plasma Markers of Alzheimer's Disease and Neurodegeneration: A Coordinated Meta-Analysis of 8 Cohort Studies

Author

Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 7a, Cardiometabolic Health, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Brain, Twait, Emma L, Kamarioti, Maria, Verberk, Inge M W, Teunissen, Charlotte E, Nooyens, Astrid C J, Monique Verschuren, W M, Visser, Pieter Jelle, Huisman, Martijn, Kok, Almar A L, Eline Slagboom, P, Beekman, Marian, Vojinovic, Dina, Lakenberg, Nico, Arfan Ikram, M, Schuurmans, Isabel K, Wolters, Frank J, Moonen, Justine E F, Gerritsen, Lotte, van der Flier, Wiesje M, Geerlings, Mirjam I, NCDC Consortium, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 7a, Cardiometabolic Health, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Brain, Twait, Emma L, Kamarioti, Maria, Verberk, Inge M W, Teunissen, Charlotte E, Nooyens, Astrid C J, Monique Verschuren, W M, Visser, Pieter Jelle, Huisman, Martijn, Kok, Almar A L, Eline Slagboom, P, Beekman, Marian, Vojinovic, Dina, Lakenberg, Nico, Arfan Ikram, M, Schuurmans, Isabel K, Wolters, Frank J, Moonen, Justine E F, Gerritsen, Lotte, van der Flier, Wiesje M, Geerlings, Mirjam I, and NCDC Consortium

Published
2024

4. Genome of The Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels.

Author

van Leeuwen, Elisabeth M, Karssen, Lennart C, Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, van Enckevort, David J, Huffman, Jennifer E, White, Charles C, Feitosa, Mary F, Bartz, Traci M, Manichaikul, Ani, Joshi, Peter K, Peloso, Gina M, Deelen, Patrick, van Dijk, Freerk, Willemsen, Gonneke, de Geus, Eco J, Milaneschi, Yuri, Penninx, Brenda WJH, Francioli, Laurent C, Menelaou, Androniki, Pulit, Sara L, Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A, Franco, Oscar H, Mateo Leach, Irene, Beekman, Marian, de Craen, Anton JM, Uh, Hae-Won, Trochet, Holly, Hocking, Lynne J, Porteous, David J, Sattar, Naveed, Packard, Chris J, Buckley, Brendan M, Brody, Jennifer A, Bis, Joshua C, Rotter, Jerome I, Mychaleckyj, Josyf C, Campbell, Harry, Duan, Qing, Lange, Leslie A, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F, Rich, Stephen S, Psaty, Bruce M, Borecki, Ingrid B, Kearney, Patricia M, Stott, David J, Adrienne Cupples, L, Genome of The Netherlands Consortium, Jukema, J Wouter, van der Harst, Pim, Sijbrands, Eric J, Hottenga, Jouke-Jan, Uitterlinden, Andre G, Swertz, Morris A, van Ommen, Gert-Jan B, de Bakker, Paul IW, Eline Slagboom, P, Boomsma, Dorret I, Wijmenga, Cisca, and van Duijn, Cornelia M

Subjects
Genome of The Netherlands Consortium, Humans, Cholesterol, ATP-Binding Cassette Transporters, Gene Frequency, Mutation, Missense, Netherlands, Genetic Association Studies, Mutation, Missense
Abstract

Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of The Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value

Published
2015

5. DNA Methylation Signatures of Educational Attainment

Author

Jenny van Dongen, Marc Jan Bonder, Koen F. Dekkers, Michel G. Nivard, Maarten van Iterson, Gonneke Willemsen, Marian Beekman, Ashley van der Spek, Joyce B. J. van Meurs, Lude Franke, Bastiaan T. Heijmans, Cornelia M. van Duijn, P. Eline Slagboom, Dorret I. Boomsma, and BIOS Consortium

Abstract

Educational attainment is a key behavioural measure in studies of cognitive and physical health, and socioeconomic status. We measured DNA methylation at 410,746 CpGs (N = 4152) and identified 58 CpGs associated with educational attainment at loci characterized by pleiotropic functions shared with neuronal, immune and developmental processes. Associations overlapped with those for smoking behaviour, but remained after accounting for smoking at many CpGs: Effect sizes were on average 28% smaller and genome-wide significant at 11 CpGs after adjusting for smoking and were 62% smaller in never smokers. We examined sources and biological implications of education-related methylation differences, demonstrating correlations with maternal prenatal folate, smoking and air pollution signatures, and associations with gene expression in cis, dynamic methylation in foetal brain, and correlations between blood and brain. Our findings show that the methylome of lower-educated people resembles that of smokers beyond effects of their own smoking behaviour and shows traces of various other exposures.

Published
2018
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7. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Author

Postmus, Iris, Trompet, Stella, Deshmukh, Harshal A, Barnes, Michael R, Li, Xiaohui, Warren, Helen R, Chasman, Daniel I, Zhou, Kaixin, Arsenault, Benoit J, Donnelly, Louise A, Wiggins, Kerri L, Avery, Christy L, Griffin, Paula, Feng, QiPing, Taylor, Kent D, Li, Guo, Evans, Daniel S, Smith, Albert V, de Keyser, Catherine E, Johnson, Andrew D, de Craen, Anton JM, Stott, David J, Buckley, Brendan M, Ford, Ian, Westendorp, Rudi GJ, Eline Slagboom, P, Sattar, Naveed, Munroe, Patricia B, Sever, Peter, Poulter, Neil, Stanton, Alice, Shields, Denis C, O’Brien, Eoin, Shaw-Hawkins, Sue, Ida Chen, Y-D, Nickerson, Deborah A, Smith, Joshua D, Pierre Dubé, Marie, Matthijs Boekholdt, S, Kees Hovingh, G, Kastelein, John JP, McKeigue, Paul M, Betteridge, John, Neil, Andrew, Durrington, Paul N, Doney, Alex, Carr, Fiona, Morris, Andrew, McCarthy, Mark I, Groop, Leif, Ahlqvist, Emma, Bis, Joshua C, Rice, Kenneth, Smith, Nicholas L, Lumley, Thomas, Whitsel, Eric A, Stürmer, Til, Boerwinkle, Eric, Ngwa, Julius S, O’Donnell, Christopher J, Vasan, Ramachandran S, Wei, Wei-Qi, Wilke, Russell A, Liu, Ching-Ti, Sun, Fangui, Guo, Xiuqing, Heckbert, Susan R, Post, Wendy, Sotoodehnia, Nona, Arnold, Alice M, Stafford, Jeanette M, Ding, Jingzhong, Herrington, David M, Kritchevsky, Stephen B, Eiriksdottir, Gudny, Launer, Leonore J, Harris, Tamara B, Chu, Audrey Y, Giulianini, Franco, MacFadyen, Jean G, Barratt, Bryan J, Nyberg, Fredrik, Stricker, Bruno H, Uitterlinden, André G, Hofman, Albert, Rivadeneira, Fernando, Emilsson, Valur, Franco, Oscar H, Ridker, Paul M, Gudnason, Vilmundur, Liu, Yongmei, Denny, Joshua C, Ballantyne, Christie M, Rotter, Jerome I, Adrienne Cupples, L, Psaty, Bruce M, Palmer, Colin NA, Tardif, Jean-Claude, Colhoun, Helen M, and Hitman, Graham

Subjects
Pharmacology and Pharmaceutical Sciences, Biological Sciences, Biomedical and Clinical Sciences, Genetics, Human Genome, 2.1 Biological and endogenous factors, Cardiovascular, Cholesterol, LDL, Genome-Wide Association Study, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pharmacogenetics, Polymorphism, Single Nucleotide, Welcome Trust Case Control Consortium
Abstract

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.

Published
2014

8. Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length: the ENGAGE consortium

Author

van der Spek, Ashley, Broer, Linda, Draisma, Harmen H. M., Pool, René, Albrecht, Eva, Beekman, Marian, Mangino, Massimo, Raag, Mait, Nyholt, Dale R., Dharuri, Harish K., Codd, Veryan, Amin, Najaf, de Geus, Eco J. C., Deelen, Joris, Demirkan, Ayse, Yet, Idil, Fischer, Krista, Haller, Toomas, Henders, Anjali K., Isaacs, Aaron, Medland, Sarah E., Montgomery, Grant W., Mooijaart, Simon P., Strauch, Konstantin, Suchiman, H. Eka D., Vaarhorst, Anika A. M., van Heemst, Diana, Wang-Sattler, Rui, Whitfield, John B., Willemsen, Gonneke, Wright, Margaret J., Martin, Nicholas G., Samani, Nilesh J., Metspalu, Andres, Eline Slagboom, P., Spector, Tim D., Boomsma, Dorret I., van Duijn, Cornelia M., and Gieger, Christian

Published
2019
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12. Genetic studies of body mass index yield new insights for obesity biology

Author

Locke, Adam E., Kahali, Bratati, Berndt, Sonja I., Justice, Anne E., Pers, Tune H., Day, Felix R., Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L., Yang, Jian, Croteau-Chonka, Damien C., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltán, Luan, Jianʼan, Mägi, Reedik, Randall, Joshua C., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Faul, Jessica D., Smith, Jennifer A., Hua Zhao, Jing, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Åsa K., Karjalainen, Juha, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L., Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B., Feenstra, Bjarke, Feitosa, Mary F., Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U., Kanoni, Stavroula, Kleber, Marcus E., Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Medland, Sarah E., Nalls, Michael A., Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Shungin, Dmitry, Stančáková, Alena, Strawbridge, Rona J., Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V., Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M., Attwood, Antony P., Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N., Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blagieva, Roza, Blüher, Matthias, Böhringer, Stefan, Bonnycastle, Lori L., Böttcher, Yvonne, Boyd, Heather A., Bruinenberg, Marcel, Caspersen, Ida H., Ida Chen, Yii-Der, Clarke, Robert, Warwick Daw, E., de Craen, Anton J. M., Delgado, Graciela, Dimitriou, Maria, Doney, Alex S. F., Eklund, Niina, Estrada, Karol, Eury, Elodie, Folkersen, Lasse, Fraser, Ross M., Garcia, Melissa E., Geller, Frank, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Goodall, Alison H., Gordon, Scott D., Gorski, Mathias, Grabe, Hans-Jörgen, Grallert, Harald, Grammer, Tanja B., Gräler, Jürgen, Grönberg, Henrik, Groves, Christopher J., Gusto, Gaëlle, Haessler, Jeffrey, Hall, Per, Haller, Toomas, Hallmans, Goran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heard-Costa, Nancy L., Helmer, Quinta, Hengstenberg, Christian, Holmen, Oddgeir, Hottenga, Jouke-Jan, James, Alan L., Jeff, Janina M., Johansson, Åsa, Jolley, Jennifer, Juliusdottir, Thorhildur, Kinnunen, Leena, Koenig, Wolfgang, Koskenvuo, Markku, Kratzer, Wolfgang, Laitinen, Jaana, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindström, Jaana, Sin Lo, Ken, Lobbens, Stéphane, Lorbeer, Roberto, Lu, Yingchang, Mach, François, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., McLachlan, Stela, Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Moayyeri, Alireza, Monda, Keri L., Morken, Mario A., Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Musk, Arthur W., Nagaraja, Ramaiah, Nöthen, Markus M., Nolte, Ilja M., Pilz, Stefan, Rayner, Nigel W., Renstrom, Frida, Rettig, Rainer, Ried, Janina S., Ripke, Stephan, Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Schumacher, Fredrick R., Scott, William R., Seufferlein, Thomas, Shi, Jianxin, Vernon Smith, Albert, Smolonska, Joanna, Stanton, Alice V., Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stringham, Heather M., Sundström, Johan, Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tyrer, Jonathan P., Uh, Hae-Won, Vandenput, Liesbeth, Verhulst, Frank C., Vermeulen, Sita H., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Warren, Helen R., Waterworth, Dawn, Weedon, Michael N., Wilkens, Lynne R., Willenborg, Christina, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Wright, Alan F., Zhang, Qunyuan, Brennan, Eoin P., Choi, Murim, Dastani, Zari, Drong, Alexander W., Eriksson, Per, Franco-Cereceda, Anders, Gådin, Jesper R., Gharavi, Ali G., Goddard, Michael E., Handsaker, Robert E., Huang, Jinyan, Karpe, Fredrik, Kathiresan, Sekar, Keildson, Sarah, Kiryluk, Krzysztof, Kubo, Michiaki, Lee, Jong-Young, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McCarroll, Steven A., McKnight, Amy J., Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Okada, Yukinori, Perry, John R. B., Dorajoo, Rajkumar, Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Scott, Robert A., Stolk, Lisette, Takahashi, Atsushi, Tanaka, Toshihiro, vanʼt Hooft, Ferdinand M., Vinkhuyzen, Anna A. E., Westra, Harm-Jan, Zheng, Wei, Zondervan, Krina T., Heath, Andrew C., Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Bovet, Pascal, Campbell, Harry, Caulfield, Mark J., Cesana, Giancarlo, Chakravarti, Aravinda, Chasman, Daniel I., Chines, Peter S., Collins, Francis S., Crawford, Dana C., Adrienne Cupples, L., Cusi, Daniele, Danesh, John, de Faire, Ulf, den Ruijter, Hester M., Dominiczak, Anna F., Erbel, Raimund, Erdmann, Jeanette, Eriksson, Johan G., Farrall, Martin, Felix, Stephan B., Ferrannini, Ele, Ferrières, Jean, Ford, Ian, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gejman, Pablo V., Gieger, Christian, Gottesman, Omri, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Alistair S., Harris, Tamara B., Hattersley, Andrew T., Hicks, Andrew A., Hindorff, Lucia A., Hingorani, Aroon D., Hofman, Albert, Homuth, Georg, Kees Hovingh, G., Humphries, Steve E., Hunt, Steven C., Hyppönen, Elina, Illig, Thomas, Jacobs, Kevin B., Jarvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Johansen, Berit, Jousilahti, Pekka, Wouter Jukema, J., Jula, Antti M., Kaprio, Jaakko, Kastelein, John J. P., Keinanen-Kiukaanniemi, Sirkka M., Kiemeney, Lambertus A., Knekt, Paul, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Moll, Frans L., Morris, Andrew D., Morris, Andrew P., Murray, Jeffrey C., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Madden, Pamela A. F., Pasterkamp, Gerard, Peden, John F., Peters, Annette, Postma, Dirkje S., Pramstaller, Peter P., Price, Jackie F., Qi, Lu, Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Rioux, John D., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schunkert, Heribert, Schwarz, Peter E. H., Sever, Peter, Shuldiner, Alan R., Sinisalo, Juha, Stolk, Ronald P., Strauch, Konstantin, Tönjes, Anke, Trégouët, David-Alexandre, Tremblay, Angelo, Tremoli, Elena, Virtamo, Jarmo, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Willemsen, Gonneke, Witteman, Jacqueline C., Carola Zillikens, M., Adair, Linda S., Amouyel, Philippe, Asselbergs, Folkert W., Assimes, Themistocles L., Bochud, Murielle, Boehm, Bernhard O., Boerwinkle, Eric, Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Cauchi, Stéphane, Chambers, John C., Chanock, Stephen J., Cooper, Richard S., de Bakker, Paul I. W., Dedoussis, George, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Groop, Leif C., Haiman, Christopher A., Hamsten, Anders, Hui, Jennie, Hunter, David J., Hveem, Kristian, Kaplan, Robert C., Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Martin, Nicholas G., März, Winfried, Melbye, Mads, Metspalu, Andres, Moebus, Susanne, Munroe, Patricia B., Njølstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Pérusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sattar, Naveed, Schadt, Eric E., Schlessinger, David, Eline Slagboom, P., Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, van der Harst, Pim, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wichmann, H-Erich, Wilson, James F., Zanen, Pieter, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Heid, Iris M., OʼConnell, Jeffrey R., Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Abecasis, Gonçalo R., Franke, Lude, Frayling, Timothy M., McCarthy, Mark I., Visscher, Peter M., Scherag, André, Willer, Cristen J., Boehnke, Michael, Mohlke, Karen L., Lindgren, Cecilia M., Beckmann, Jacques S., Barroso, Inês, North, Kari E., Ingelsson, Erik, Hirschhorn, Joel N., Loos, Ruth J. F., and Speliotes, Elizabeth K.

Published
2015
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13. New genetic loci link adipose and insulin biology to body fat distribution

Author

Shungin, Dmitry, Winkler, Thomas W., Croteau-Chonka, Damien C., Ferreira, Teresa, Locke, Adam E., Mägi, Reedik, Strawbridge, Rona J., Pers, Tune H., Fischer, Krista, Justice, Anne E., Workalemahu, Tsegaselassie, Wu, Joseph M. W., Buchkovich, Martin L., Heard-Costa, Nancy L., Roman, Tamara S., Drong, Alexander W., Song, Ci, Gustafsson, Stefan, Day, Felix R., Esko, Tonu, Fall, Tove, Kutalik, Zoltán, Luan, Jianʼan, Randall, Joshua C., Scherag, André, Vedantam, Sailaja, Wood, Andrew R., Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Ehret, Georg B., Feitosa, Mary F., Goel, Anuj, Jackson, Anne U., Johnson, Toby, Kleber, Marcus E., Kristiansson, Kati, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Stančáková, Alena, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V., Yengo, Loïc, Zhang, Weihua, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M., Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blüher, Matthias, Böhringer, Stefan, Bonnet, Fabrice, Böttcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B., Caspersen, Ida H., Clarke, Robert, Warwick Daw, E., Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex S. F., Eklund, Niina, Erdos, Michael R., Estrada, Karol, Eury, Elodie, Friedrich, Nele, Garcia, Melissa E., Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Grallert, Harald, Grammer, Tanja B., Gräler, Jürgen, Grewal, Jagvir, Groves, Christopher J., Haller, Toomas, Hallmans, Goran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heikkilä, Kauko, Herzig, Karl-Heinz, Helmer, Quinta, Hillege, Hans L., Holmen, Oddgeir, Hunt, Steven C., Isaacs, Aaron, Ittermann, Till, James, Alan L., Johansson, Ingegerd, Juliusdottir, Thorhildur, Kalafati, Ioanna-Panagiota, Kinnunen, Leena, Koenig, Wolfgang, Kooner, Ishminder K., Kratzer, Wolfgang, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindström, Jaana, Lobbens, Stéphane, Lorentzon, Mattias, Mach, François, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Moayyeri, Alireza, Monda, Keri L., Mooijaart, Simon P., Mühleisen, Thomas W., Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Nagaraja, Ramaiah, Nalls, Michael A., Narisu, Narisu, Glorioso, Nicola, Nolte, Ilja M., Olden, Matthias, Rayner, Nigel W., Renstrom, Frida, Ried, Janina S., Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Sennblad, Bengt, Seufferlein, Thomas, Sitlani, Colleen M., Vernon Smith, Albert, Stirrups, Kathleen, Stringham, Heather M., Sundström, Johan, Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tomaschitz, Andreas, Troffa, Chiara, van Oort, Floor V. A., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Wennauer, Roman, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Zhang, Qunyuan, Hua Zhao, Jing, Brennan, Eoin P., Choi, Murim, Eriksson, Per, Folkersen, Lasse, Franco-Cereceda, Anders, Gharavi, Ali G., Hedman, Åsa K., Hivert, Marie-France, Huang, Jinyan, Kanoni, Stavroula, Karpe, Fredrik, Keildson, Sarah, Kiryluk, Krzysztof, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McKnight, Amy J., McPherson, Ruth, Metspalu, Andres, Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Olsson, Christian, Perry, John R. B., Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Schadt, Eric E., Scott, Robert A., Stolk, Lisette, Vallejo, Edgar E., Westra, Harm-Jan, Zondervan, Krina T., Amouyel, Philippe, Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Brown, Morris J., Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chines, Peter S., Claudi-Boehm, Simone, Collins, Francis S., Crawford, Dana C., Danesh, John, de Faire, Ulf, de Geus, Eco J. C., Dörr, Marcus, Erbel, Raimund, Eriksson, Johan G., Farrall, Martin, Ferrannini, Ele, Ferrières, Jean, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gieger, Christian, Gudnason, Vilmundur, Haiman, Christopher A., Harris, Tamara B., Hattersley, Andrew T., Heliövaara, Markku, Hicks, Andrew A., Hingorani, Aroon D., Hoffmann, Wolfgang, Hofman, Albert, Homuth, Georg, Humphries, Steve E., Hyppönen, Elina, Illig, Thomas, Jarvelin, Marjo-Riitta, Johansen, Berit, Jousilahti, Pekka, Jula, Antti M., Kaprio, Jaakko, Kee, Frank, Keinanen-Kiukaanniemi, Sirkka M., Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Musk, Arthur W., Möhlenkamp, Stefan, Morris, Andrew D., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Palmer, Lyle J., Penninx, Brenda W., Peters, Annette, Pramstaller, Peter P., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schwarz, Peter E. H., Shuldiner, Alan R., Staessen, Jan A., Steinthorsdottir, Valgerdur, Stolk, Ronald P., Strauch, Konstantin, Tönjes, Anke, Tremblay, Angelo, Tremoli, Elena, Vohl, Marie-Claude, Völker, Uwe, Vollenweider, Peter, Wilson, James F., Witteman, Jacqueline C., Adair, Linda S., Bochud, Murielle, Boehm, Bernhard O., Bornstein, Stefan R., Bouchard, Claude, Cauchi, Stéphane, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Cooper, Richard S., Dedoussis, George, Ferrucci, Luigi, Froguel, Philippe, Grabe, Hans-Jörgen, Hamsten, Anders, Hui, Jennie, Hveem, Kristian, Jöckel, Karl-Heinz, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, März, Winfried, Munroe, Patricia B., Njølstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Pérusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sinisalo, Juha, Eline Slagboom, P., Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, van der Harst, Pim, Veronesi, Giovanni, Walker, Mark, Wareham, Nicholas J., Watkins, Hugh, Wichmann, H-Erich, Abecasis, Goncalo R., Assimes, Themistocles L., Berndt, Sonja I., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Franke, Lude, Frayling, Timothy M., Groop, Leif C., Hunter, David J., Kaplan, Robert C., OʼConnell, Jeffrey R., Qi, Lu, Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Willer, Cristen J., Visscher, Peter M., Yang, Jian, Hirschhorn, Joel N., Carola Zillikens, M., McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Fox, Caroline S., Barroso, Inês, Franks, Paul W., Ingelsson, Erik, Heid, Iris M., Loos, Ruth J. F., Cupples, Adrienne L., Morris, Andrew P., Lindgren, Cecilia M., and Mohlke, Karen L

Published
2015
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17. Metabolic Age Based on the BBMRI-NL H-1-NMR Metabolomics Repository as Biomarker of Age-related Disease

Author

Akker, E.B. van den, Trompet, S., Barkey Wolf, Jurriaan J.H., Beekman, M., Suchiman, H. Eka D., Deelen, J., Netea, M.G., Reinders, M.J.T., Eline Slagboom, P., Akker, E.B. van den, Trompet, S., Barkey Wolf, Jurriaan J.H., Beekman, M., Suchiman, H. Eka D., Deelen, J., Netea, M.G., Reinders, M.J.T., and Eline Slagboom, P.

Abstract

Contains fulltext : 227384.pdf (Publisher’s version ) (Closed access)

Published
2020

18. Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa

Author

Duncan, Laramie, Yilmaz, Zeynep, Gaspar, Helena, Walters, Raymond, Goldstein, Jackie, Anttila, Verneri, Bulik-Sullivan, Brendan, Ripke, Stephan, Thornton, Laura, Hinney, Anke, Daly, Mark, Sullivan, Patrick F., Zeggini, Eleftheria, Breen, Gerome, Bulik, Cynthia M., Gaspar, Héléna, Adan, Roger, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole, Aschauer, Harald, Baker, Jessica, Barrett, Jeffrey, Bencko, Vladimir, Bergen, Andrew, Berrettini, Wade, Birgegård, Andreas, Boni, Claudette, Perica, Vesna Boraska, Brandt, Harry, Burghardt, Roland, Carlberg, Laura, Cassina, Matteo, Cesta, Carolyn, Cichon, Sven, Clementi, Maurizio, Cohen-Woods, Sarah, Coleman, Joni, Cone, Roger, Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, Jim, Danner, Unna, Davis, Oliver, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, Desocio, Janiece, Danielle, Dick, Dikeos, Dimitris, Dina, Christian, Ding, Bo, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Espeseth, Thomas, Estivill, Xavier, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred, Finan, Chris, Fischer, Krista, Floyd, James, Föcker, Manuel, Foretova, Lenka, Forzan, Monica, Fox, Caroline, Franklin, Christopher, Gaborieau, Valerie, Gallinger, Steven, Gambaro, Giovanni, Giegling, Ina, Gonidakis, Fragiskos, Gorwood, Philip, Gratacos, Monica, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine, Harrison, Rebecca, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske, Hendriks, Judith, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hilliard, Christopher, Huckins, Laura, Hudson, James, Huemer, Julia, Imgart, Hartmut, Inoko, Hidetoshi, Jall, Sigrid, Jamain, Stephane, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jenny, Julià, Antonio, Juréus, Anders, Kalsi, Gursharan, Kaplan, Allan, Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien, Kaye, Walter, Kennedy, Martin, Kennedy, James, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Klareskog, Lars, Klump, Kelly, Knudsen, Gun Peggy, Koeleman, Bobby, Koubek, Doris, La Via, Maria, Landén, Mikael, Le Hellard, Stephanie, Leboyer, Marion, Levitan, Robert, Dong, Li, Lichtenstein, Paul, Lilenfeld, Lisa, Lissowska, Jolanta, Lundervold, Astri, Magistretti, Pierre, Maj, Mario, Mannik, Katrin, Marsal, Sara, Kaminska, Debora, Martin, Nicholas, Mattingsdal, Morten, Mcdevitt, Sara, Mcguffin, Peter, Merl, Elisabeth, Metspalu, Andres, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, James, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Montgomery, Grant, Mortensen, Preben, Munn-Chernoff, Melissa, Müller, Timo, Nacmias, Benedetta, Navratilova, Marie, Nilsson, Ida, Norring, Claes, Ntalla, Ioanna, Ophoff, Roel, O’Toole, Julie, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Parker, Richard, Pinto, Dalila, Rabionet, Raquel, Raevuori, Anu, Rajewski, Andrzej, Ramoz, Nicolas, William Rayner, N., Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen, Schmidt, Ulrike, Schork, Nicholas, Schosser, Alexandra, Scott, Laura, Seitz, Jochen, Slachtova, Lenka, Sladek, Robert, Eline Slagboom, P., Slof-Op ’t Landt, Margarita, Slopien, Agnieszka, Smith, Tosha, Soranzo, Nicole, Sorbi, Sandro, Southam, Lorraine, Steen, Vidar, Strengman, Eric, Strober, Michael, Szatkiewicz, Jin, Szeszenia-Dabrowska, Neonila, Tachmazidou, Ioanna, Tenconi, Elena, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tschöp, Matthias, Tsitsika, Artemis, Tziouvas, Konstantinos, van Elburg, Annemarie, van Furth, Eric, Wade, Tracey, Wagner, Gudrun, Walton, Esther, Watson, Hunna, Wichmann, H-Erich, Widen, Elisabeth, Woodside, Blake, Yanovski, Jack, Yao, Shuyang, Zerwas, Stephanie, Zipfel, Stephan, Duncan, Laramie, Yilmaz, Zeynep, Gaspar, Helena, Walters, Raymond, Goldstein, Jackie, Anttila, Verneri, Bulik-Sullivan, Brendan, Ripke, Stephan, Thornton, Laura, Hinney, Anke, Daly, Mark, Sullivan, Patrick F., Zeggini, Eleftheria, Breen, Gerome, Bulik, Cynthia M., Gaspar, Hã©lã©na, Adan, Roger, Alfredsson, Lar, Ando, Tetsuya, Andreassen, Ole, Aschauer, Harald, Baker, Jessica, Barrett, Jeffrey, Bencko, Vladimir, Bergen, Andrew, Berrettini, Wade, Birgegã¥rd, Andrea, Boni, Claudette, Perica, Vesna Boraska, Brandt, Harry, Burghardt, Roland, Carlberg, Laura, Cassina, Matteo, Cesta, Carolyn, Cichon, Sven, Clementi, Maurizio, Cohen-Woods, Sarah, Coleman, Joni, Cone, Roger, Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, Jim, Danner, Unna, Davis, Oliver, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, Desocio, Janiece, Danielle, Dick, Dikeos, Dimitri, Dina, Christian, Ding, Bo, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Egberts, Karin, Ehrlich, Stefan, Escaramã­s, Geã²rgia, Esko, Tãµnu, Espeseth, Thoma, Estivill, Xavier, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred, Finan, Chri, Fischer, Krista, Floyd, Jame, Fã¶cker, Manuel, Foretova, Lenka, Forzan, Monica, Fox, Caroline, Franklin, Christopher, Gaborieau, Valerie, Gallinger, Steven, Gambaro, Giovanni, Giegling, Ina, Gonidakis, Fragisko, Gorwood, Philip, Gratacos, Monica, Guillaume, Sã©bastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine, Harrison, Rebecca, Hatzikotoulas, Konstantino, Hauser, Joanna, Hebebrand, Johanne, Helder, Sietske, Hendriks, Judith, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hilliard, Christopher, Huckins, Laura, Hudson, Jame, Huemer, Julia, Imgart, Hartmut, Inoko, Hidetoshi, Jall, Sigrid, Jamain, Stephane, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jenny, Juliã , Antonio, Jurã©us, Ander, Kalsi, Gursharan, Kaplan, Allan, Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andrea, Kas, Martien, Kaye, Walter, Kennedy, Martin, Kennedy, Jame, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Klareskog, Lar, Klump, Kelly, Knudsen, Gun Peggy, Koeleman, Bobby, Koubek, Dori, La Via, Maria, Landã©n, Mikael, Le Hellard, Stephanie, Leboyer, Marion, Levitan, Robert, Li, Dong, Lichtenstein, Paul, Lilenfeld, Lisa, Lissowska, Jolanta, Lundervold, Astri, Magistretti, Pierre, Maj, Mario, Mannik, Katrin, Marsal, Sara, Kaminska, Debora, Martin, Nichola, Mattingsdal, Morten, Mcdevitt, Sara, Mcguffin, Peter, Merl, Elisabeth, Metspalu, Andre, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, Jame, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Montgomery, Grant, Mortensen, Preben, Munn-Chernoff, Melissa, Mã¼ller, Timo, Nacmias, Benedetta, Navratilova, Marie, Nilsson, Ida, Norring, Clae, Ntalla, Ioanna, Ophoff, Roel, Oâ toole, Julie, Palotie, Aarno, Pantel, Jacque, Papezova, Hana, Parker, Richard, Pinto, Dalila, Rabionet, Raquel, Raevuori, Anu, Rajewski, Andrzej, Ramoz, Nicola, William Rayner, N., Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, Rybakowski, Filip, Santonastaso, Paolo, Scherag, Andrã©, Scherer, Stephen, Schmidt, Ulrike, Schork, Nichola, Schosser, Alexandra, Scott, Laura, Seitz, Jochen, Slachtova, Lenka, Sladek, Robert, Eline Slagboom, P., Slof-Op â t Landt, Margarita, Slopien, Agnieszka, Smith, Tosha, Soranzo, Nicole, Sorbi, Sandro, Southam, Lorraine, Steen, Vidar, Strengman, Eric, Strober, Michael, Szatkiewicz, Jin, Szeszenia-Dabrowska, Neonila, Tachmazidou, Ioanna, Tenconi, Elena, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tschã¶p, Matthia, Tsitsika, Artemi, Tziouvas, Konstantino, van Elburg, Annemarie, van Furth, Eric, Wade, Tracey, Wagner, Gudrun, Walton, Esther, Watson, Hunna, Wichmann, H-Erich, Widen, Elisabeth, Woodside, Blake, Yanovski, Jack, Yao, Shuyang, Zerwas, Stephanie, Zipfel, Stephan, Universitat de Barcelona, and Kas lab

Subjects
0301 basic medicine, Linkage disequilibrium, Anorexia Nervosa, Eating Disorders, Medizin, Genome-wide association study, Diabete, Linkage Disequilibrium, Diabetes, GWAS, Genetics, Metabolism, Case-Control Studies, Genetic Predisposition to Disease, Humans, Phenotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Psychiatry and Mental Health, 0302 clinical medicine, Anorexia Nervosa/genetics, SCHIZOPHRENIA, Gwas, RISK, Genetic Predisposition to Disease/genetics, PSYCHIATRIC-DISORDERS, Anorèxia nerviosa, Eating Disorder, Single Nucleotide, Polymorphism, Single Nucleotide/genetics, Metabolisme, Psychiatry and Mental health, Psychology, Case-Control Studie, TRAITS, Human, Polymorphism, Single-nucleotide polymorphism, behavioral disciplines and activities, Article, Feeding and Eating Disorders, 03 medical and health sciences, Genetic, mental disorders, Journal Article, Linkage Disequilibrium/genetics, 1000 Genomes Project, Bulimia Nervosa, METAANALYSIS, Genetic association, EATING-DISORDERS, Settore MED/13 - ENDOCRINOLOGIA, Anorexia nervosa, Heritability, Minor allele frequency, 030104 developmental biology, UPDATE, 030217 neurology & neurosurgery, Imputation (genetics), Genètica, Meta-Analysis
Abstract

Objective: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Method: Following uniformquality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3, 495 anorexia nervosa cases and 10, 982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2 SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes. Results: Results were obtained for 10, 641, 224 SNPs and insertion-deletion variants with minor allele frequencies.>1% and imputation quality scores >0.6. The h2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Conclusions: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genomewide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

Published
2017
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19. Integrated clinical and omics approach to rare diseases : Novel genes and oligogenic inheritance in holoprosencephaly

Author

Kim, Artem, Savary, Clara, Dubourg, Christèle, Carré, Wilfrid, Mouden, Charlotte, Hamdi-Rozé, Houda, Guyodo, Hélène, Douce, Jerome Le, Génin, Emmanuelle, Campion, Dominique, Dartigues, Jean François, Deleuze, Jean François, Lambert, Jean Charles, Redon, Richard, Ludwig, Thomas, Grenier-Boley, Benjamin, Letort, Sébastien, Lindenbaum, Pierre, Meyer, Vincent, Quenez, Olivier, Dina, Christian, Bellenguez, Céline, Charbonnier-Le Clézio, Camille, Giemza, Joanna, Chatel, Stéphanie, Férec, Claude, Le Marec, Hervé, Letenneur, Luc, Nicolas, Gaël, Rouault, Karen, Bacq, Delphine, Boland, Anne, Lechner, Doris, Wijmenga, Cisca, Swertz, Morris A., Eline Slagboom, P., Van Ommen, Gert Jan B., Van Duijn, Cornelia M., Boomsma, Dorret I., De Bakker, Paul I.W., Bovenberg, Jasper A., De Craen, Anton J.M., Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Sujie Cao, Jeremy, Van Dijk, Freerk, Neerincx, Pieter B.T., Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Vermaat, Martijn, Laros, Jeroen F.J., Den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Mathijs Kattenberg, V., Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D.C., Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., Guryev, Victor, Pasquier, Laurent, Flori, Elisabeth, Gonzales, Marie, Bénéteau, Claire, Boute, Odile, Attié-Bitach, Tania, Roume, Joelle, Goujon, Louise, Akloul, Linda, Odent, Sylvie, Watrin, Erwan, Dupé, Valérie, De Tayrac, Marie, David, Véronique, Kim, Artem, Savary, Clara, Dubourg, Christèle, Carré, Wilfrid, Mouden, Charlotte, Hamdi-Rozé, Houda, Guyodo, Hélène, Douce, Jerome Le, Génin, Emmanuelle, Campion, Dominique, Dartigues, Jean François, Deleuze, Jean François, Lambert, Jean Charles, Redon, Richard, Ludwig, Thomas, Grenier-Boley, Benjamin, Letort, Sébastien, Lindenbaum, Pierre, Meyer, Vincent, Quenez, Olivier, Dina, Christian, Bellenguez, Céline, Charbonnier-Le Clézio, Camille, Giemza, Joanna, Chatel, Stéphanie, Férec, Claude, Le Marec, Hervé, Letenneur, Luc, Nicolas, Gaël, Rouault, Karen, Bacq, Delphine, Boland, Anne, Lechner, Doris, Wijmenga, Cisca, Swertz, Morris A., Eline Slagboom, P., Van Ommen, Gert Jan B., Van Duijn, Cornelia M., Boomsma, Dorret I., De Bakker, Paul I.W., Bovenberg, Jasper A., De Craen, Anton J.M., Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Sujie Cao, Jeremy, Van Dijk, Freerk, Neerincx, Pieter B.T., Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Vermaat, Martijn, Laros, Jeroen F.J., Den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Mathijs Kattenberg, V., Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D.C., Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., Guryev, Victor, Pasquier, Laurent, Flori, Elisabeth, Gonzales, Marie, Bénéteau, Claire, Boute, Odile, Attié-Bitach, Tania, Roume, Joelle, Goujon, Louise, Akloul, Linda, Odent, Sylvie, Watrin, Erwan, Dupé, Valérie, De Tayrac, Marie, and David, Véronique

Published
2019

20. Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length: the ENGAGE consortium

Author

Spek, A. (Ashley) van der, Boer, L (Linda), Draisma, G. (Gerrit), Pool, R. (Reńe), Albrecht, E. (Eva), Beekman, M. (Marian), Mangino, M. (Massimo), Raag, M. (Mait), Nyholt, D.R. (Dale R.), Dharuri, H. (Harish), Codd, V. (Veryan), Amin, N (Najaf), de Geus, E.J.C. (Eco J. C.), Deelen, J. (Joris), Demirkan, A. (Ayşe), Yet, I. (Idil), Fischer, K. (Krista), Haller, T. (Toomas), Henders, A.K. (Anjali K.), Isaacs, A. (Aaron), Medland, S.E. (Sarah E.), Montgomery, G.W. (Grant W.), Mooijaart, S.P. (Simon), Strauch, K. (Konstantin), Suchiman, H.E.D. (H. Eka D.), Vaarhorst, A.A.M. (Anika), Heemst, D. (Diana) van, Wang-Sattler, R. (Rui), Whitfield, J. (John), Willemsen, G. (Gonneke), Wright, M.J. (Margaret J.), Martin, N.G. (Nicholas), Samani, N.J. (Nilesh J.), Metspalu, A. (Andres), Eline Slagboom, P. (P.), Spector, T.D. (Tim D.), Boomsma, D.I. (Dorret I.), Duijn, C.M. (Cornelia) van, Gieger, C. (Christian), Spek, A. (Ashley) van der, Boer, L (Linda), Draisma, G. (Gerrit), Pool, R. (Reńe), Albrecht, E. (Eva), Beekman, M. (Marian), Mangino, M. (Massimo), Raag, M. (Mait), Nyholt, D.R. (Dale R.), Dharuri, H. (Harish), Codd, V. (Veryan), Amin, N (Najaf), de Geus, E.J.C. (Eco J. C.), Deelen, J. (Joris), Demirkan, A. (Ayşe), Yet, I. (Idil), Fischer, K. (Krista), Haller, T. (Toomas), Henders, A.K. (Anjali K.), Isaacs, A. (Aaron), Medland, S.E. (Sarah E.), Montgomery, G.W. (Grant W.), Mooijaart, S.P. (Simon), Strauch, K. (Konstantin), Suchiman, H.E.D. (H. Eka D.), Vaarhorst, A.A.M. (Anika), Heemst, D. (Diana) van, Wang-Sattler, R. (Rui), Whitfield, J. (John), Willemsen, G. (Gonneke), Wright, M.J. (Margaret J.), Martin, N.G. (Nicholas), Samani, N.J. (Nilesh J.), Metspalu, A. (Andres), Eline Slagboom, P. (P.), Spector, T.D. (Tim D.), Boomsma, D.I. (Dorret I.), Duijn, C.M. (Cornelia) van, and Gieger, C. (Christian)

Abstract

Telomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10−6), methionine (p-value = 9.2 × 10−5), tyrosine (p-value = 2.1 × 10−4), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10−4), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10−4), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10−4). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality.

Published
2019
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21. Integrated clinical and omics approach to rare diseases: Novel genes and oligogenic inheritance in holoprosencephaly

Author

CMM Groep Kaaij, Genetica Klinische Genetica, Cancer, CMM Groep De Ridder, Child Health, CMM Groep Kloosterman, CMM USEQ Facility, Hubrecht Institute with UMC, Kim, Artem, Savary, Clara, Dubourg, Christèle, Carré, Wilfrid, Mouden, Charlotte, Hamdi-Rozé, Houda, Guyodo, Hélène, Douce, Jerome Le, Génin, Emmanuelle, Campion, Dominique, Dartigues, Jean François, Deleuze, Jean François, Lambert, Jean Charles, Redon, Richard, Ludwig, Thomas, Grenier-Boley, Benjamin, Letort, Sébastien, Lindenbaum, Pierre, Meyer, Vincent, Quenez, Olivier, Dina, Christian, Bellenguez, Céline, Charbonnier-Le Clézio, Camille, Giemza, Joanna, Chatel, Stéphanie, Férec, Claude, Le Marec, Hervé, Letenneur, Luc, Nicolas, Gaël, Rouault, Karen, Bacq, Delphine, Boland, Anne, Lechner, Doris, Wijmenga, Cisca, Swertz, Morris A., Eline Slagboom, P., Van Ommen, Gert Jan B., Van Duijn, Cornelia M., Boomsma, Dorret I., De Bakker, Paul I.W., Bovenberg, Jasper A., De Craen, Anton J.M., Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Sujie Cao, Jeremy, Van Dijk, Freerk, Neerincx, Pieter B.T., Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Vermaat, Martijn, Laros, Jeroen F.J., Den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Mathijs Kattenberg, V., Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D.C., Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., Guryev, Victor, Pasquier, Laurent, Flori, Elisabeth, Gonzales, Marie, Bénéteau, Claire, Boute, Odile, Attié-Bitach, Tania, Roume, Joelle, Goujon, Louise, Akloul, Linda, Odent, Sylvie, Watrin, Erwan, Dupé, Valérie, De Tayrac, Marie, David, Véronique, CMM Groep Kaaij, Genetica Klinische Genetica, Cancer, CMM Groep De Ridder, Child Health, CMM Groep Kloosterman, CMM USEQ Facility, Hubrecht Institute with UMC, Kim, Artem, Savary, Clara, Dubourg, Christèle, Carré, Wilfrid, Mouden, Charlotte, Hamdi-Rozé, Houda, Guyodo, Hélène, Douce, Jerome Le, Génin, Emmanuelle, Campion, Dominique, Dartigues, Jean François, Deleuze, Jean François, Lambert, Jean Charles, Redon, Richard, Ludwig, Thomas, Grenier-Boley, Benjamin, Letort, Sébastien, Lindenbaum, Pierre, Meyer, Vincent, Quenez, Olivier, Dina, Christian, Bellenguez, Céline, Charbonnier-Le Clézio, Camille, Giemza, Joanna, Chatel, Stéphanie, Férec, Claude, Le Marec, Hervé, Letenneur, Luc, Nicolas, Gaël, Rouault, Karen, Bacq, Delphine, Boland, Anne, Lechner, Doris, Wijmenga, Cisca, Swertz, Morris A., Eline Slagboom, P., Van Ommen, Gert Jan B., Van Duijn, Cornelia M., Boomsma, Dorret I., De Bakker, Paul I.W., Bovenberg, Jasper A., De Craen, Anton J.M., Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Sujie Cao, Jeremy, Van Dijk, Freerk, Neerincx, Pieter B.T., Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Vermaat, Martijn, Laros, Jeroen F.J., Den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Mathijs Kattenberg, V., Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D.C., Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., Guryev, Victor, Pasquier, Laurent, Flori, Elisabeth, Gonzales, Marie, Bénéteau, Claire, Boute, Odile, Attié-Bitach, Tania, Roume, Joelle, Goujon, Louise, Akloul, Linda, Odent, Sylvie, Watrin, Erwan, Dupé, Valérie, De Tayrac, Marie, and David, Véronique

Published
2019

22. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Author

Postmus, Iris, Trompet, Stella, Deshmukh, Harshal A., Barnes, Michael R., Li, Xiaohui, Warren, Helen R., Chasman, Daniel I., Zhou, Kaixin, Arsenault, Benoit J., Donnelly, Louise A., Wiggins, Kerri L., Avery, Christy L., Griffin, Paula, Feng, QiPing, Taylor, Kent D., Li, Guo, Evans, Daniel S., Smith, Albert V., de Keyser, Catherine E., Johnson, Andrew D., de Craen, Anton J.M., Stott, David J., Buckley, Brendan M., Ford, Ian, Westendorp, Rudi G. J., Eline Slagboom, P., Sattar, Naveed, Munroe, Patricia B., Sever, Peter, Poulter, Neil, Stanton, Alice, Shields, Denis C., O’Brien, Eoin, Shaw-Hawkins, Sue, Ida Chen, Y.-D., Nickerson, Deborah A., Smith, Joshua D., Pierre Dubé, Marie, Matthijs Boekholdt, S., Kees Hovingh, G., Kastelein, John J.P., McKeigue, Paul M., Betteridge, John, Neil, Andrew, Durrington, Paul N., Doney, Alex, Carr, Fiona, Morris, Andrew, McCarthy, Mark I., Groop, Leif, Ahlqvist, Emma, Bis, Joshua C., Rice, Kenneth, Smith, Nicholas L., Lumley, Thomas, Whitsel, Eric A., Stürmer, Til, Boerwinkle, Eric, Ngwa, Julius S., O’Donnell, Christopher J., Vasan, Ramachandran S., Wei, Wei-Qi, Wilke, Russell A., Liu, Ching-Ti, Sun, Fangui, Guo, Xiuqing, Heckbert, Susan R, Post, Wendy, Sotoodehnia, Nona, Arnold, Alice M., Stafford, Jeanette M., Ding, Jingzhong, Herrington, David M., Kritchevsky, Stephen B., Eiriksdottir, Gudny, Launer, Leonore J., Harris, Tamara B., Chu, Audrey Y., Giulianini, Franco, MacFadyen, Jean G., Barratt, Bryan J., Nyberg, Fredrik, Stricker, Bruno H., Uitterlinden, André G., Hofman, Albert, Rivadeneira, Fernando, Emilsson, Valur, Franco, Oscar H., Ridker, Paul M., Gudnason, Vilmundur, Liu, Yongmei, Denny, Joshua C., Ballantyne, Christie M., Rotter, Jerome I., Adrienne Cupples, L., Psaty, Bruce M., Palmer, Colin N.A., Tardif, Jean-Claude, Colhoun, Helen M., Hitman, Graham, Krauss, Ronald M., Wouter Jukema, J, Caulfield, Mark J., Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M., Bramon, Elvira, Brown, Matthew A., Casas, Juan P., Corvin, Aiden, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S., Mathew, Christopher G., Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J., Trembath, Richard C., Viswanathan, Ananth C., Wood, Nicholas W., Spencer, Chris C.A., Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard, Strange, Amy, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Hunt, Sarah E., Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J., Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T., Liddle, Jennifer, Potter, Simon C., Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Erasmus MC other, Epidemiology, Internal Medicine, ACS - Amsterdam Cardiovascular Sciences, Cardiology, and Vascular Medicine

Subjects
Apolipoprotein E, BLOOD, LOCI, General Physics and Astronomy, Genome-wide association study, VARIANTS, 030204 cardiovascular system & hematology, Pharmacology, Bioinformatics, THERAPY, DISEASE, chemistry.chemical_compound, 0302 clinical medicine, GENE-EXPRESSION, 0303 health sciences, Multidisciplinary, biology, 3. Good health, Multidisciplinary Sciences, Meta-analysis, WHOLE-GENOME, Science & Technology - Other Topics, lipids (amino acids, peptides, and proteins), Statin, medicine.drug_class, Endocrinology and Diabetes, Polymorphism, Single Nucleotide, INDUCED MYOPATHY, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, medicine, Humans, cardiovascular diseases, 030304 developmental biology, Genetic association, Science & Technology, Cholesterol, business.industry, HUMAN PREFRONTAL CORTEX, nutritional and metabolic diseases, General Chemistry, Cholesterol, LDL, A300, chemistry, Pharmacogenetics, biology.protein, PLASMA LIPOPROTEIN(A) LEVELS, Hydroxymethylglutaryl-CoA Reductase Inhibitors, SLCO1B1, business, Genome-Wide Association Study
Abstract

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response., Statins are effectively used to prevent and manage cardiovascular disease, but patient response to these drugs is highly variable. Here, the authors identify two new genes associated with the response of LDL cholesterol to statins and advance our understanding of the genetic basis of drug response.

Published
2016
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23. A high-quality reference panel reveals the complexity and distribution of structural genome changes in a human population

Author

Jayne Y. Hehir-Kwa, van Ommen Gb, Dijkstra Lj, Guryev, Wigard P. Kloosterman, Andre G. Uitterlinden, Eric-Wubbo Lameijer, Patrick Deelen, de Bakker P, Kai Ye, Thung Dt, René Wardenaar, Alexander Schoenhuth, van Dijk F, Bradley P. Coe, Laurent C. Francioli, Jasmijn A. Baaijens, Ivo Renkens, de Ligt J, Eline Slagboom P, Evan E. Eichler, Fereydoun Hormozdiari, Cisca Wijmenga, Dorret I. Boomsma, Abdel Abdellaoui, Koval, Morris A. Swertz, and Tobias Marschall

Subjects
Genetics, 0303 health sciences, Linkage disequilibrium, education.field_of_study, Population, Computational biology, Biology, Genome, Structural variation, 03 medical and health sciences, 0302 clinical medicine, Human genome, Mobile genetic elements, education, 030217 neurology & neurosurgery, Imputation (genetics), 030304 developmental biology, Genetic association
Abstract

Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, current studies on SVs have failed to provide a global view of the full spectrum of SVs and to integrate them into reference panels of genetic variation. Here, we analyzed 769 individuals from 250 Dutch families, whole genome sequenced at an average coverage of 14.5x, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels and retrotransposition-mediated insertions of mobile elements and processed RNAs. A large proportion of the structural variants (36%) were discovered in the size range of 21 to 100bp, a size range which remains under reported in many studies. Furthermore, we detected 4 megabases of novel sequence, extending the human pangenome with 11 new active transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with a structural variant and demonstrate that our panel facilitates accurate imputation of SVs into unrelated individuals, which is essential for future genome-wide association studies.

Published
2016
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24. Corrigendum: DNA methylation signatures link prenatal famine exposure to growth and metabolism

Author

Tobi, Elmar W., Goeman, Jelle J., Monajemi, Ramin, Gu, Hongcang, Putter, Hein, Zhang, Yanju, Slieker, Roderick C., Stok, Arthur P., Thijssen, Peter E., Müller, Fabian, van Zwet, Erik W., Bock, Christoph, Meissner, Alexander, Lumey, L. H., Eline Slagboom, P., Heijmans, Bastiaan T., Epidemiology and Data Science, APH - Aging & Later Life, and APH - Health Behaviors & Chronic Diseases

Subjects
Male, Carnitine O-Palmitoyltransferase, Molecular Sequence Data, DNA Methylation, Fetal Nutrition Disorders, Middle Aged, Corrigenda, Receptor, Insulin, Epigenesis, Genetic, Fetal Development, Antigens, CD, Pregnancy, Starvation, Prenatal Exposure Delayed Effects, Birth Weight, Humans, Female, Netherlands
Abstract

Periconceptional diet may persistently influence DNA methylation levels with phenotypic consequences. However, a comprehensive assessment of the characteristics of prenatal malnutrition-associated differentially methylated regions (P-DMRs) is lacking in humans. Here we report on a genome-scale analysis of differential DNA methylation in whole blood after periconceptional exposure to famine during the Dutch Hunger Winter. We show that P-DMRs preferentially occur at regulatory regions, are characterized by intermediate levels of DNA methylation and map to genes enriched for differential expression during early development. Validation and further exploratory analysis of six P-DMRs highlight the critical role of gestational timing. Interestingly, differential methylation of the P-DMRs extends along pathways related to growth and metabolism. P-DMRs located in INSR and CPT1A have enhancer activity in vitro and differential methylation is associated with birth weight and serum LDL cholesterol. Epigenetic modulation of pathways by prenatal malnutrition may promote an adverse metabolic phenotype in later life.

Published
2015
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25. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Author

Van Leeuwen, EM, Karssen, LC, Deelen, J, Isaacs, A, Medina-Gomez, C, Mbarek, H, Kanterakis, A, Trompet, S, Postmus, I, Verweij, N, Van Enckevort, DJ, Huffman, JE, White, CC, Feitosa, MF, Bartz, TM, Manichaikul, A, Joshi, PK, Peloso, GM, Deelen, P, Van Dijk, F, Willemsen, G, De Geus, EJ, Milaneschi, Y, Penninx, BWJH, Francioli, LC, Menelaou, A, Pulit, SL, Rivadeneira, F, Hofman, A, Oostra, BA, Franco, OH, Leach, IM, Beekman, M, De Craen, AJM, Uh, HW, Trochet, H, Hocking, LJ, Porteous, DJ, Sattar, N, Packard, CJ, Buckley, BM, Brody, JA, Bis, JC, Rotter, JI, Mychaleckyj, JC, Campbell, H, Duan, Q, Lange, LA, Wilson, JF, Hayward, C, Polasek, O, Vitart, V, Rudan, I, Wright, AF, Rich, SS, Psaty, BM, Borecki, IB, Kearney, PM, Stott, DJ, Cupples, LA, Jukema, JW, Van Der Harst, P, Sijbrands, EJ, Hottenga, JJ, Uitterlinden, AG, Swertz, MA, Van Ommen, GJB, De Bakker, PIW, Eline Slagboom, P, Boomsma, DI, Wijmenga, C, Van Duijn, CM, Neerincx, PBT, Elbers, CC, Palamara, PF, Peer, I, Abdellaoui, A, Kloosterman, WP, Van Oven, M, Vermaat, M, Li, M, Laros, JFJ, Stoneking, M, De Knijff, P, Kayser, M, Veldink, JH, Van Den Berg, LH, Byelas, H, Den Dunnen, JT, Dijkstra, M, Amin, N, Van Der Velde, KJ, and Van Setten, J

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (∼35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value

Published
2015
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26. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author

Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, Loos, Ruth J F, Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, and Loos, Ruth J F

Abstract

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

Published
2016
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27. Genetic variants determining survival and fertility in an adverse African environment: A population-based large-scale candidate gene association study

Author

Koopman, Jacob J.E., Pijpe, Jeroen, Böhringer, Stefan, van Bodegom, David, Eriksson, Ulrika K., Sanchez-Faddeev, Hernando, Ziem, Juventus B., Zwaan, Bas, Eline Slagboom, P., de Knijff, Peter, Westendorp, Rudi G.J., Koopman, Jacob J.E., Pijpe, Jeroen, Böhringer, Stefan, van Bodegom, David, Eriksson, Ulrika K., Sanchez-Faddeev, Hernando, Ziem, Juventus B., Zwaan, Bas, Eline Slagboom, P., de Knijff, Peter, and Westendorp, Rudi G.J.

Abstract

Human survival probability and fertility decline strongly with age. These life history traits have been shaped by evolution. However, research has failed to uncover a consistent genetic determination of variation in survival and fertility. As an explanation, such genetic determinants have been selected in adverse environments, in which humans have lived during most of their history, but are almost exclusively studied in populations in modern affluent environments. Here, we present a large-scale candidate gene association study in a rural African population living in an adverse environment. In 4387 individuals, we studied 4052 SNPs in 148 genes that have previously been identified as possible determinants of survival or fertility in animals or humans. We studied their associations with survival comparing newborns, middle-age adults, and old individuals. In women, we assessed their associations with reported and observed numbers of children. We found no statistically significant associations of these SNPs with survival between the three age groups nor with women's reported and observed fertility. Population stratification was unlikely to explain these results. Apart from a lack of power, we hypothesise that genetic heterogeneity of complex phenotypes and gene -environment interactions prevent the identification of genetic variants explaining variation in survival and fertility in humans.

Published
2016

28. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Author

de Craen, Anton J. M., Chasman, Daniel I., Poulter, Neil, Postmus, Iris, de Keyser, Catherine E., Stott, David J., Avery, Christy L., Donnelly, Louise A., Barnes, Michael R., Johnson, Andrew D., Deshmukh, Harshal A., Zhou, Kaixin, Buckley, Brendan M., Evans, Daniel S., Li, Guo, Eline Slagboom, P., Wiggins, Kerri L., Sattar, Naveed, Shields, Denis C., Warren, Helen R., Munroe, Patricia B., Taylor, Kent D., Westendorp, Rudi G. J., Sever, Peter, Li, Xiaohui, Trompet, Stella, Arsenault, Benoit J., Feng, QiPing, Smith, Albert V., Ford, Ian, Griffin, Paula, and Stanton, Alice

Subjects
nutritional and metabolic diseases, lipids (amino acids, peptides, and proteins), cardiovascular diseases
Abstract

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response. Statins are effectively used to prevent and manage cardiovascular disease, but patient response to these drugs is highly variable. Here, the authors identify two new genes associated with the response of LDL cholesterol to statins and advance our understanding of the genetic basis of drug response.

Published
2014
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29. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author

Kilpeläinen, Tuomas O., primary, Carli, Jayne F. Martin, additional, Skowronski, Alicja A., additional, Sun, Qi, additional, Kriebel, Jennifer, additional, Feitosa, Mary F, additional, Hedman, Åsa K., additional, Drong, Alexander W., additional, Hayes, James E., additional, Zhao, Jinghua, additional, Pers, Tune H., additional, Schick, Ursula, additional, Grarup, Niels, additional, Kutalik, Zoltán, additional, Trompet, Stella, additional, Mangino, Massimo, additional, Kristiansson, Kati, additional, Beekman, Marian, additional, Lyytikäinen, Leo-Pekka, additional, Eriksson, Joel, additional, Henneman, Peter, additional, Lahti, Jari, additional, Tanaka, Toshiko, additional, Luan, Jian’an, additional, Greco M, Fabiola Del, additional, Pasko, Dorota, additional, Renström, Frida, additional, Willems, Sara M., additional, Mahajan, Anubha, additional, Rose, Lynda M., additional, Guo, Xiuqing, additional, Liu, Yongmei, additional, Kleber, Marcus E., additional, Pérusse, Louis, additional, Gaunt, Tom, additional, Ahluwalia, Tarunveer S., additional, Ju Sung, Yun, additional, Ramos, Yolande F., additional, Amin, Najaf, additional, Amuzu, Antoinette, additional, Barroso, Inês, additional, Bellis, Claire, additional, Blangero, John, additional, Buckley, Brendan M., additional, Böhringer, Stefan, additional, I Chen, Yii-Der, additional, de Craen, Anton J. N., additional, Crosslin, David R., additional, Dale, Caroline E., additional, Dastani, Zari, additional, Day, Felix R., additional, Deelen, Joris, additional, Delgado, Graciela E., additional, Demirkan, Ayse, additional, Finucane, Francis M., additional, Ford, Ian, additional, Garcia, Melissa E., additional, Gieger, Christian, additional, Gustafsson, Stefan, additional, Hallmans, Göran, additional, Hankinson, Susan E., additional, Havulinna, Aki S, additional, Herder, Christian, additional, Hernandez, Dena, additional, Hicks, Andrew A., additional, Hunter, David J., additional, Illig, Thomas, additional, Ingelsson, Erik, additional, Ioan-Facsinay, Andreea, additional, Jansson, John-Olov, additional, Jenny, Nancy S., additional, Jørgensen, Marit E., additional, Jørgensen, Torben, additional, Karlsson, Magnus, additional, Koenig, Wolfgang, additional, Kraft, Peter, additional, Kwekkeboom, Joanneke, additional, Laatikainen, Tiina, additional, Ladwig, Karl-Heinz, additional, LeDuc, Charles A., additional, Lowe, Gordon, additional, Lu, Yingchang, additional, Marques-Vidal, Pedro, additional, Meisinger, Christa, additional, Menni, Cristina, additional, Morris, Andrew P., additional, Myers, Richard H., additional, Männistö, Satu, additional, Nalls, Mike A., additional, Paternoster, Lavinia, additional, Peters, Annette, additional, Pradhan, Aruna D., additional, Rankinen, Tuomo, additional, Rasmussen-Torvik, Laura J., additional, Rathmann, Wolfgang, additional, Rice, Treva K., additional, Brent Richards, J, additional, Ridker, Paul M., additional, Sattar, Naveed, additional, Savage, David B., additional, Söderberg, Stefan, additional, Timpson, Nicholas J., additional, Vandenput, Liesbeth, additional, van Heemst, Diana, additional, Uh, Hae-Won, additional, Vohl, Marie-Claude, additional, Walker, Mark, additional, Wichmann, Heinz-Erich, additional, Widén, Elisabeth, additional, Wood, Andrew R., additional, Yao, Jie, additional, Zeller, Tanja, additional, Zhang, Yiying, additional, Meulenbelt, Ingrid, additional, Kloppenburg, Margreet, additional, Astrup, Arne, additional, Sørensen, Thorkild I. A., additional, Sarzynski, Mark A., additional, Rao, D. C., additional, Jousilahti, Pekka, additional, Vartiainen, Erkki, additional, Hofman, Albert, additional, Rivadeneira, Fernando, additional, Uitterlinden, André G., additional, Kajantie, Eero, additional, Osmond, Clive, additional, Palotie, Aarno, additional, Eriksson, Johan G., additional, Heliövaara, Markku, additional, Knekt, Paul B., additional, Koskinen, Seppo, additional, Jula, Antti, additional, Perola, Markus, additional, Huupponen, Risto K., additional, Viikari, Jorma S., additional, Kähönen, Mika, additional, Lehtimäki, Terho, additional, Raitakari, Olli T., additional, Mellström, Dan, additional, Lorentzon, Mattias, additional, Casas, Juan P., additional, Bandinelli, Stefanie, additional, März, Winfried, additional, Isaacs, Aaron, additional, van Dijk, Ko W., additional, van Duijn, Cornelia M., additional, Harris, Tamara B., additional, Bouchard, Claude, additional, Allison, Matthew A., additional, Chasman, Daniel I., additional, Ohlsson, Claes, additional, Lind, Lars, additional, Scott, Robert A., additional, Langenberg, Claudia, additional, Wareham, Nicholas J., additional, Ferrucci, Luigi, additional, Frayling, Timothy M., additional, Pramstaller, Peter P., additional, Borecki, Ingrid B., additional, Waterworth, Dawn M., additional, Bergmann, Sven, additional, Waeber, Gérard, additional, Vollenweider, Peter, additional, Vestergaard, Henrik, additional, Hansen, Torben, additional, Pedersen, Oluf, additional, Hu, Frank B., additional, Eline Slagboom, P, additional, Grallert, Harald, additional, Spector, Tim D., additional, Jukema, J.W., additional, Klein, Robert J., additional, Schadt, Erik E, additional, Franks, Paul W., additional, Lindgren, Cecilia M., additional, Leibel, Rudolph L., additional, and Loos, Ruth J. F., additional

Published
2016
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30. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Author

Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, and Bovenberg, Jasper A.

Published
2015

31. Genetic studies of body mass index yield new insights for obesity biology

Author

Locke, Adam E, Kahali, Bratati, Berndt, Sonja I, Justice, Anne E, Pers, Tune H, Day, Felix R, Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L, Yang, Jian, Croteau-Chonka, Damien C, Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltán, Luan, Jian'an, Mägi, Reedik, Randall, Joshua C, Winkler, Thomas W, Wood, Andrew R, Workalemahu, Tsegaselassie, Faul, Jessica D, Smith, Jennifer A, Hua Zhao, Jing, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Åsa K, Karjalainen, Juha, Schmidt, Ellen M, Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L, Bragg-Gresham, Jennifer L, Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B, Feenstra, Bjarke, Feitosa, Mary F, Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U, Kanoni, Stavroula, Kleber, Marcus E, Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Medland, Sarah E, Nalls, Michael A, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J, Prokopenko, Inga, Shungin, Dmitry, Stančáková, Alena, Strawbridge, Rona J, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V, Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M, Attwood, Antony P, Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blagieva, Roza, Blüher, Matthias, Böhringer, Stefan, Bonnycastle, Lori L, Böttcher, Yvonne, Boyd, Heather A, Bruinenberg, Marcel, Caspersen, Ida H, Ida Chen, Yii-Der, Clarke, Robert, Warwick Daw, E, de Craen, Anton J M, Delgado, Graciela, Dimitriou, Maria, Doney, Alex S F, Eklund, Niina, Estrada, Karol, Eury, Elodie, Folkersen, Lasse, Fraser, Ross M, Garcia, Melissa E, Geller, Frank, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S, Golay, Alain, Goodall, Alison H, Gordon, Scott D, Gorski, Mathias, Grabe, Hans-Jörgen, Grallert, Harald, Grammer, Tanja B, Gräßler, Jürgen, Grönberg, Henrik, Groves, Christopher J, Gusto, Gaëlle, Haessler, Jeffrey, Hall, Per, Haller, Toomas, Hallmans, Goran, Hartman, Catharina A, Hassinen, Maija, Hayward, Caroline, Heard-Costa, Nancy L, Helmer, Quinta, Hengstenberg, Christian, Holmen, Oddgeir, Hottenga, Jouke-Jan, James, Alan L, Jeff, Janina M, Johansson, Åsa, Jolley, Jennifer, Juliusdottir, Thorhildur, Kinnunen, Leena, Koenig, Wolfgang, Koskenvuo, Markku, Kratzer, Wolfgang, Laitinen, Jaana, Lamina, Claudia, Leander, Karin, Lee, Nanette R, Lichtner, Peter, Lind, Lars, Lindström, Jaana, Sin Lo, Ken, Lobbens, Stéphane, Lorbeer, Roberto, Lu, Yingchang, Mach, François, Magnusson, Patrik K E, Mahajan, Anubha, McArdle, Wendy L, McLachlan, Stela, Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Moayyeri, Alireza, Monda, Keri L, Morken, Mario A, Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Musk, Arthur W, Nagaraja, Ramaiah, Nöthen, Markus M, Nolte, Ilja M, Pilz, Stefan, Rayner, Nigel W, Renstrom, Frida, Rettig, Rainer, Ried, Janina S, Ripke, Stephan, Robertson, Neil R, Rose, Lynda M, Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Schumacher, Fredrick R, Scott, William R, Seufferlein, Thomas, Shi, Jianxin, Vernon Smith, Albert, Smolonska, Joanna, Stanton, Alice V, Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stringham, Heather M, Sundström, Johan, Swertz, Morris A, Swift, Amy J, Syvänen, Ann-Christine, Tan, Sian-Tsung, Tayo, Bamidele O, Thorand, Barbara, Thorleifsson, Gudmar, Tyrer, Jonathan P, Uh, Hae-Won, Vandenput, Liesbeth, Verhulst, Frank C, Vermeulen, Sita H, Verweij, Niek, Vonk, Judith M, Waite, Lindsay L, Warren, Helen R, Waterworth, Dawn, Weedon, Michael N, Wilkens, Lynne R, Willenborg, Christina, Wilsgaard, Tom, Wojczynski, Mary K, Wong, Andrew, Wright, Alan F, Zhang, Qunyuan, Brennan, Eoin P, Choi, Murim, Dastani, Zari, Drong, Alexander W, Eriksson, Per, Franco-Cereceda, Anders, Gådin, Jesper R, Gharavi, Ali G, Goddard, Michael E, Handsaker, Robert E, Huang, Jinyan, Karpe, Fredrik, Kathiresan, Sekar, Keildson, Sarah, Kiryluk, Krzysztof, Kubo, Michiaki, Lee, Jong-Young, Liang, Liming, Lifton, Richard P, Ma, Baoshan, McCarroll, Steven A, McKnight, Amy J, Min, Josine L, Moffatt, Miriam F, Montgomery, Grant W, Murabito, Joanne M, Nicholson, George, Nyholt, Dale R, Okada, Yukinori, Perry, John R B, Dorajoo, Rajkumar, Reinmaa, Eva, Salem, Rany M, Sandholm, Niina, Scott, Robert A, Stolk, Lisette, Takahashi, Atsushi, Tanaka, Toshihiro, Van't Hooft, Ferdinand M, Vinkhuyzen, Anna A E, Westra, Harm-Jan, Zheng, Wei, Zondervan, Krina T, Heath, Andrew C, Arveiler, Dominique, Bakker, Stephan J L, Beilby, John, Bergman, Richard N, Blangero, John, Bovet, Pascal, Campbell, Harry, Caulfield, Mark J, Cesana, Giancarlo, Chakravarti, Aravinda, Chasman, Daniel I, Chines, Peter S, Collins, Francis S, Crawford, Dana C, Adrienne Cupples, L, Cusi, Daniele, Danesh, John, de 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M, Scherag, André, Willer, Cristen J, Boehnke, Michael, Mohlke, Karen L, Lindgren, Cecilia M, Beckmann, Jacques S, Barroso, Inês, North, Kari E, Ingelsson, Erik, Hirschhorn, Joel N, Loos, Ruth J F, and Speliotes, Elizabeth K

Abstract

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis., De fem sista författarna delar sistaförfattarskapet.

Published
2015
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32. New genetic loci link adipose and insulin biology to body fat distribution

Author

UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Shungin, Dmitry, Winkler, Thomas W., Croteau-Chonka, Damien C., Ferreira, Teresa, Locke, Adam E., Mägi, Reedik, Strawbridge, Rona J., Pers, Tune H., Fischer, Krista, Justice, Anne E., Workalemahu, Tsegaselassie, Wu, Joseph M. W., Buchkovich, Martin L., Heard-Costa, Nancy L., Roman, Tamara S., Drong, Alexander W., Song, Ci, Gustafsson, Stefan, Day, Felix R., Esko, Tonu, Fall, Tove, Kutalik, Zoltán, Luan, Jian’an, Randall, Joshua C., Scherag, André, Vedantam, Sailaja, Wood, Andrew R., Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Ehret, Georg B., Feitosa, Mary F., Goel, Anuj, Jackson, Anne U., Johnson, Toby, Kleber, Marcus E., Kristiansson, Kati, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Stančáková, Alena, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V., Yengo, Loïc, Zhang, Weihua, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M., Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blüher, Matthias, Böhringer, Stefan, Bonnet, Fabrice, Böttcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B., Caspersen, Ida H., Clarke, Robert, Warwick Daw, E., Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex S. F., Eklund, Niina, Erdos, Michael R., Estrada, Karol, Eury, Elodie, Friedrich, Nele, Garcia, Melissa E., Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Grallert, Harald, Grammer, Tanja B., Gräßler, Jürgen, Grewal, Jagvir, Groves, Christopher J., Haller, Toomas, Hallmans, Goran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heikkilä, Kauko, Herzig, Karl-Heinz, Helmer, Quinta, Hillege, Hans L., Holmen, Oddgeir, Hunt, Steven C., Isaacs, Aaron, Ittermann, Till, James, Alan L., Johansson, Ingegerd, Juliusdottir, Thorhildur, Kalafati, Ioanna-Panagiota, Kinnunen, Leena, Koenig, Wolfgang, Kooner, Ishminder K., Kratzer, Wolfgang, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindström, Jaana, Lobbens, Stéphane, Lorentzon, Mattias, Mach, François, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Moayyeri, Alireza, Monda, Keri L., Mooijaart, Simon P., Mühleisen, Thomas W., Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Nagaraja, Ramaiah, Nalls, Michael A., Narisu, Narisu, Glorioso, Nicola, Nolte, Ilja M., Olden, Matthias, Rayner, Nigel W., Renstrom, Frida, Ried, Janina S., Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Sennblad, Bengt, Seufferlein, Thomas, Sitlani, Colleen M., Vernon Smith, Albert, Stirrups, Kathleen, Stringham, Heather M., Sundström, Johan, Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tomaschitz, Andreas, Troffa, Chiara, van Oort, Floor V. A., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Wennauer, Roman, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Zhang, Qunyuan, Hua Zhao, Jing, Brennan, Eoin P., Choi, Murim, Eriksson, Per, Folkersen, Lasse, Franco-Cereceda, Anders, Gharavi, Ali G., Hedman, Åsa K., Hivert, Marie-France, Huang, Jinyan, Kanoni, Stavroula, Karpe, Fredrik, Keildson, Sarah, Kiryluk, Krzysztof, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McKnight, Amy J., McPherson, Ruth, Metspalu, Andres, Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Olsson, Christian, Perry, John R. B., Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Schadt, Eric E., Scott, Robert A., Stolk, Lisette, Vallejo, Edgar E., Westra, Harm-Jan, Zondervan, Krina T., Amouyel, Philippe, Arveiler, Dominique, Bakker, Stephan J. 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C., Dörr, Marcus, Erbel, Raimund, Eriksson, Johan G., Farrall, Martin, Ferrannini, Ele, Ferrières, Jean, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gieger, Christian, Gudnason, Vilmundur, Haiman, Christopher A., Harris, Tamara B., Hattersley, Andrew T., Heliövaara, Markku, Hicks, Andrew A., Hingorani, Aroon D., Hoffmann, Wolfgang, Hofman, Albert, Homuth, Georg, Humphries, Steve E., Hyppönen, Elina, Illig, Thomas, Jarvelin, Marjo-Riitta, Johansen, Berit, Jousilahti, Pekka, Jula, Antti M., Kaprio, Jaakko, Kee, Frank, Keinanen-Kiukaanniemi, Sirkka M., Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Musk, Arthur W., Möhlenkamp, Stefan, Morris, Andrew D., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Palmer, Lyle J., Penninx, Brenda W., Peters, Annette, Pramstaller, Peter P., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schwarz, Peter E. H., Shuldiner, Alan R., Staessen, Jan A., Steinthorsdottir, Valgerdur, Stolk, Ronald P., Strauch, Konstantin, Tönjes, Anke, Tremblay, Angelo, Tremoli, Elena, Vohl, Marie-Claude, Völker, Uwe, Vollenweider, Peter, Wilson, James F., Witteman, Jacqueline C., Adair, Linda S., Bochud, Murielle, Boehm, Bernhard O., Bornstein, Stefan R., Bouchard, Claude, Cauchi, Stéphane, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Cooper, Richard S., Dedoussis, George, Ferrucci, Luigi, Froguel, Philippe, Grabe, Hans-Jörgen, Hamsten, Anders, Hui, Jennie, Hveem, Kristian, Jöckel, Karl-Heinz, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, März, Winfried, Munroe, Patricia B., Njølstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Pérusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sinisalo, Juha, Eline Slagboom, P., Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, van der Harst, Pim, Veronesi, Giovanni, Walker, Mark, Wareham, Nicholas J., Watkins, Hugh, Wichmann, H-Erich, Abecasis, Goncalo R., Assimes, Themistocles L., Berndt, Sonja I., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Franke, Lude, Frayling, Timothy M., Groop, Leif C., Hunter, David J., Kaplan, Robert C., O’Connell, Jeffrey R., Qi, Lu, Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Willer, Cristen J., Visscher, Peter M., Yang, Jian, Hirschhorn, Joel N., Carola Zillikens, M., McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Fox, Caroline S., Barroso, Inês, Franks, Paul W., Ingelsson, Erik, Heid, Iris M., Loos, Ruth J. F., Cupples, L. Adrienne, Morris, Andrew P., Lindgren, Cecilia M., Mohlke, Karen L, Devuyst, Olivier, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Shungin, Dmitry, Winkler, Thomas W., Croteau-Chonka, Damien C., Ferreira, Teresa, Locke, Adam E., Mägi, Reedik, Strawbridge, Rona J., Pers, Tune H., Fischer, Krista, Justice, Anne E., Workalemahu, Tsegaselassie, Wu, Joseph M. W., Buchkovich, Martin L., Heard-Costa, Nancy L., Roman, Tamara S., Drong, Alexander W., Song, Ci, Gustafsson, Stefan, Day, Felix R., Esko, Tonu, Fall, Tove, Kutalik, Zoltán, Luan, Jian’an, Randall, Joshua C., Scherag, André, Vedantam, Sailaja, Wood, Andrew R., Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Ehret, Georg B., Feitosa, Mary F., Goel, Anuj, Jackson, Anne U., Johnson, Toby, Kleber, Marcus E., Kristiansson, Kati, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Stančáková, Alena, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V., Yengo, Loïc, Zhang, Weihua, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M., Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blüher, Matthias, Böhringer, Stefan, Bonnet, Fabrice, Böttcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B., Caspersen, Ida H., Clarke, Robert, Warwick Daw, E., Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex S. F., Eklund, Niina, Erdos, Michael R., Estrada, Karol, Eury, Elodie, Friedrich, Nele, Garcia, Melissa E., Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Grallert, Harald, Grammer, Tanja B., Gräßler, Jürgen, Grewal, Jagvir, Groves, Christopher J., Haller, Toomas, Hallmans, Goran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heikkilä, Kauko, Herzig, Karl-Heinz, Helmer, Quinta, Hillege, Hans L., Holmen, Oddgeir, Hunt, Steven C., Isaacs, Aaron, Ittermann, Till, James, Alan L., Johansson, Ingegerd, Juliusdottir, Thorhildur, Kalafati, Ioanna-Panagiota, Kinnunen, Leena, Koenig, Wolfgang, Kooner, Ishminder K., Kratzer, Wolfgang, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindström, Jaana, Lobbens, Stéphane, Lorentzon, Mattias, Mach, François, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Moayyeri, Alireza, Monda, Keri L., Mooijaart, Simon P., Mühleisen, Thomas W., Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Nagaraja, Ramaiah, Nalls, Michael A., Narisu, Narisu, Glorioso, Nicola, Nolte, Ilja M., Olden, Matthias, Rayner, Nigel W., Renstrom, Frida, Ried, Janina S., Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Sennblad, Bengt, Seufferlein, Thomas, Sitlani, Colleen M., Vernon Smith, Albert, Stirrups, Kathleen, Stringham, Heather M., Sundström, Johan, Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tomaschitz, Andreas, Troffa, Chiara, van Oort, Floor V. A., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Wennauer, Roman, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Zhang, Qunyuan, Hua Zhao, Jing, Brennan, Eoin P., Choi, Murim, Eriksson, Per, Folkersen, Lasse, Franco-Cereceda, Anders, Gharavi, Ali G., Hedman, Åsa K., Hivert, Marie-France, Huang, Jinyan, Kanoni, Stavroula, Karpe, Fredrik, Keildson, Sarah, Kiryluk, Krzysztof, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McKnight, Amy J., McPherson, Ruth, Metspalu, Andres, Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Olsson, Christian, Perry, John R. B., Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Schadt, Eric E., Scott, Robert A., Stolk, Lisette, Vallejo, Edgar E., Westra, Harm-Jan, Zondervan, Krina T., Amouyel, Philippe, Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Brown, Morris J., Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chines, Peter S., Claudi-Boehm, Simone, Collins, Francis S., Crawford, Dana C., Danesh, John, de Faire, Ulf, de Geus, Eco J. C., Dörr, Marcus, Erbel, Raimund, Eriksson, Johan G., Farrall, Martin, Ferrannini, Ele, Ferrières, Jean, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gieger, Christian, Gudnason, Vilmundur, Haiman, Christopher A., Harris, Tamara B., Hattersley, Andrew T., Heliövaara, Markku, Hicks, Andrew A., Hingorani, Aroon D., Hoffmann, Wolfgang, Hofman, Albert, Homuth, Georg, Humphries, Steve E., Hyppönen, Elina, Illig, Thomas, Jarvelin, Marjo-Riitta, Johansen, Berit, Jousilahti, Pekka, Jula, Antti M., Kaprio, Jaakko, Kee, Frank, Keinanen-Kiukaanniemi, Sirkka M., Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Musk, Arthur W., Möhlenkamp, Stefan, Morris, Andrew D., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Palmer, Lyle J., Penninx, Brenda W., Peters, Annette, Pramstaller, Peter P., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schwarz, Peter E. H., Shuldiner, Alan R., Staessen, Jan A., Steinthorsdottir, Valgerdur, Stolk, Ronald P., Strauch, Konstantin, Tönjes, Anke, Tremblay, Angelo, Tremoli, Elena, Vohl, Marie-Claude, Völker, Uwe, Vollenweider, Peter, Wilson, James F., Witteman, Jacqueline C., Adair, Linda S., Bochud, Murielle, Boehm, Bernhard O., Bornstein, Stefan R., Bouchard, Claude, Cauchi, Stéphane, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Cooper, Richard S., Dedoussis, George, Ferrucci, Luigi, Froguel, Philippe, Grabe, Hans-Jörgen, Hamsten, Anders, Hui, Jennie, Hveem, Kristian, Jöckel, Karl-Heinz, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, März, Winfried, Munroe, Patricia B., Njølstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Pérusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sinisalo, Juha, Eline Slagboom, P., Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, van der Harst, Pim, Veronesi, Giovanni, Walker, Mark, Wareham, Nicholas J., Watkins, Hugh, Wichmann, H-Erich, Abecasis, Goncalo R., Assimes, Themistocles L., Berndt, Sonja I., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Franke, Lude, Frayling, Timothy M., Groop, Leif C., Hunter, David J., Kaplan, Robert C., O’Connell, Jeffrey R., Qi, Lu, Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Willer, Cristen J., Visscher, Peter M., Yang, Jian, Hirschhorn, Joel N., Carola Zillikens, M., McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Fox, Caroline S., Barroso, Inês, Franks, Paul W., Ingelsson, Erik, Heid, Iris M., Loos, Ruth J. F., Cupples, L. Adrienne, Morris, Andrew P., Lindgren, Cecilia M., Mohlke, Karen L, and Devuyst, Olivier

Published
2015

33. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Author

CMM Groep Kaaij, CMM Groep Kloosterman, Child Health, Cancer, ZL Neuromusculaire Ziekten Medisch, Experimentele Afd. Cardiologie 1, CMM Groep Cuppen, JC onderzoeksprogramma Methodologie, Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., de Bakker, Paul I W, CMM Groep Kaaij, CMM Groep Kloosterman, Child Health, Cancer, ZL Neuromusculaire Ziekten Medisch, Experimentele Afd. Cardiologie 1, CMM Groep Cuppen, JC onderzoeksprogramma Methodologie, Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., and de Bakker, Paul I W

Published
2015

34. Correction: Corrigendum: DNA methylation signatures link prenatal famine exposure to growth and metabolism

Author

Tobi, Elmar W., primary, Goeman, Jelle J., additional, Monajemi, Ramin, additional, Gu, Hongcang, additional, Putter, Hein, additional, Zhang, Yanju, additional, Slieker, Roderick C., additional, Stok, Arthur P., additional, Thijssen, Peter E., additional, Müller, Fabian, additional, van Zwet, Erik W., additional, Bock, Christoph, additional, Meissner, Alexander, additional, Lumey, L. H., additional, Eline Slagboom, P., additional, and Heijmans, Bastiaan T., additional

Published
2015
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35. Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels

Author

Draisma, Harmen H. M., primary, Pool, René, additional, Kobl, Michael, additional, Jansen, Rick, additional, Petersen, Ann-Kristin, additional, Vaarhorst, Anika A. M., additional, Yet, Idil, additional, Haller, Toomas, additional, Demirkan, Ayşe, additional, Esko, Tõnu, additional, Zhu, Gu, additional, Böhringer, Stefan, additional, Beekman, Marian, additional, van Klinken, Jan Bert, additional, Römisch-Margl, Werner, additional, Prehn, Cornelia, additional, Adamski, Jerzy, additional, de Craen, Anton J. M., additional, van Leeuwen, Elisabeth M., additional, Amin, Najaf, additional, Dharuri, Harish, additional, Westra, Harm-Jan, additional, Franke, Lude, additional, de Geus, Eco J. C., additional, Hottenga, Jouke Jan, additional, Willemsen, Gonneke, additional, Henders, Anjali K., additional, Montgomery, Grant W., additional, Nyholt, Dale R., additional, Whitfield, John B., additional, Penninx, Brenda W., additional, Spector, Tim D., additional, Metspalu, Andres, additional, Eline Slagboom, P., additional, van Dijk, Ko Willems, additional, ‘t Hoen, Peter A. C., additional, Strauch, Konstantin, additional, Martin, Nicholas G., additional, van Ommen, Gert-Jan B., additional, Illig, Thomas, additional, Bell, Jordana T., additional, Mangino, Massimo, additional, Suhre, Karsten, additional, McCarthy, Mark I., additional, Gieger, Christian, additional, Isaacs, Aaron, additional, van Duijn, Cornelia M., additional, and Boomsma, Dorret I., additional

Published
2015
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36. Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers

Author

Deelen, Joris, primary, Beekman, Marian, additional, Codd, Veryan, additional, Trompet, Stella, additional, Broer, Linda, additional, Hägg, Sara, additional, Fischer, Krista, additional, Thijssen, Peter E, additional, Suchiman, H Eka D, additional, Postmus, Iris, additional, Uitterlinden, André G, additional, Hofman, Albert, additional, de Craen, Anton J M, additional, Metspalu, Andres, additional, Pedersen, Nancy L, additional, van Duijn, Cornelia M, additional, Wouter Jukema, J, additional, Houwing-Duistermaat, Jeanine J, additional, Samani, Nilesh J, additional, and Eline Slagboom, P, additional

Published
2014
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37. Genetica: een panacea II

Author

Boomsma, Dorret, Eline Slagboom, P., APH - Methodology, APH - Mental Health, and Biological Psychology

Subjects
Netherlands Twin Register (NTR)
Published
1998

39. Genetic and environmental influences interact with age and sex in shaping the human methylome.

Author

van Dongen, Jenny, Nivard, Michel G., Willemsen, Gonneke, Hottenga, Jouke-Jan, Helmer, Quinta, Dolan, Conor V., Ehli, Erik A., Davies, Gareth E., van Iterson, Maarten, Breeze, Charles E., Beck, Stephan, Eka Suchiman, H., Jansen, Rick, van Meurs, Joyce B., Heijmans, Bastiaan T., Eline Slagboom, P., Boomsma, Dorret I., Hoen, Peter A. C. 't, Pool, René, and van Greevenbroek, Marleen M. J.

Published
2016
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41. This title is unavailable for guests, please login to see more information.

Author

Van Meurs, Joyce B.J., Arp, Pascal P., Fang, Yue, Eline Slagboom, P., Meulenbelt, Ingrid, Van Leeuwen, Johannes P.T.M., Pols, Huibert A.P., Uitterlinden, André G., Van Meurs, Joyce B.J., Arp, Pascal P., Fang, Yue, Eline Slagboom, P., Meulenbelt, Ingrid, Van Leeuwen, Johannes P.T.M., Pols, Huibert A.P., and Uitterlinden, André G.

Abstract

The variable number of tandem repeat (VNTR) 3' of the collagen type II (COL2A1) gene has been shown to be highly variable with a complex molecular structure. In a previous pilot experiment we observed discordance between methods to genotype this informative marker. To further investigate the extent and molecular nature of this discordance, we genotyped a random sample of 207 Caucasian individuals with two genotyping methods and sequenced new alleles. We compared single-strand (SS) analysis, which is based on detection of size differences between the different alleles, and heteroduplex analysis (HA), which is sensitive to both size and sequence differences. Overall, 26% of discordance between the two methods was detected. Approximately two thirds of this discordance was caused by subdivision of SS-alleles 13R1 and 14R2 into HA-alleles 4A + 4B and 3B + 3C, respectively. Sequence analysis of the COL2A1-VNTR alleles 4B and 3C showed that these alleles differed in sequence, but not in size, from already described SS-alleles, which explains why they escape detection by SS. The 4B allele is a frequent allele in the population (14%) and is, therefore, important to distinguish in association studies. We conclude that HA is a reliable method when the described optimized electrophoretic conditions are used. HA is a sensitive genotyping method to document allelic diversity at this locus, which can distinguish more alleles compared to the SS method.

Published
2000

45. Variation in the SHC1 gene and longevity in humans

Author

Mooijaart, Simon P, primary, van Heemst, Diana, additional, Schreuder, Jeroen, additional, van Gerwen, Suzan, additional, Beekman, Marian, additional, Brandt, Bernd W, additional, Eline Slagboom, P, additional, and Westendorp, Rudi G.J, additional

Published
2004
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46. Identification and systematic annotation of tissue-specific differentially methylated regions using the Illumina 450k array.

Author

Slieker, Roderick C., Bos, Steffan D., Goeman, Jelle J., Bovée, Judith V.M.G., Talens, Rudolf P., van der Breggen, Ruud, Suchiman, H. Eka D., Lameijer, Eric-Wubbo, Putter, Hein, van den Akker, Erik B., Zhang, Yanju, Wouter Jukema, J., Eline Slagboom, P, Meulenbelt, Ingrid, and Heijmans, Bastiaan T.

Subjects
DNA methylation, CELL differentiation, GENOMICS, TRANSCRIPTION factors, EXONS (Genetics)
Abstract

Background: DNA methylation has been recognized as a key mechanism in cell differentiation. Various studies have compared tissues to characterize epigenetically regulated genomic regions, but due to differences in study design and focus there still is no consensus as to the annotation of genomic regions predominantly involved in tissue-specific methylation. We used a new algorithm to identify and annotate tissue-specific differentially methylated regions (tDMRs) from Illumina 450k chip data for four peripheral tissues (blood, saliva, buccal swabs and hair follicles) and six internal tissues (liver, muscle, pancreas, subcutaneous fat, omentum and spleen with matched blood samples). Results: The majority of tDMRs, in both relative and absolute terms, occurred in CpG-poor regions. Further analysis revealed that these regions were associated with alternative transcription events (alternative first exons, mutually exclusive exons and cassette exons). Only a minority of tDMRs mapped to gene-body CpG islands (13%) or CpG islands shores (25%) suggesting a less prominent role for these regions than indicated previously. Implementation of ENCODE annotations showed enrichment of tDMRs in DNase hypersensitive sites and transcription factor binding sites. Despite the predominance of tissue differences, inter-individual differences in DNA methylation in internal tissues were correlated with those for blood for a subset of CpG sites in a locus- and tissue-specific manner. Conclusions: We conclude that tDMRs preferentially occur in CpG-poor regions and are associated with alternative transcription. Furthermore, our data suggest the utility of creating an atlas cataloguing variably methylated regions in internal tissues that correlate to DNA methylation measured in easy accessible peripheral tissues. [ABSTRACT FROM AUTHOR]

Published
2013
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47. Prenatal Famine and Genetic Variation Are Independently and Additively Associated with DNA Methylation at Regulatory Loci within IGF2/H19.

Author

Tobi, Elmar W., Eline Slagboom, P., Van Dongen, Jenny, Kremer, Dennis, Stein, Aryeh D., Putter, Hein, Heijmans, Bastiaan T., and Lumey, L. H.

Subjects
*HUMAN genetic variation, *DNA methylation, *GENETIC regulation, *INSULIN-like growth factor-binding proteins, *GENETIC polymorphisms, *EPIGENETICS
Abstract

Both the early environment and genetic variation may affect DNA methylation, which is one of the major molecular marks of the epigenome. The combined effect of these factors on a well-defined locus has not been studied to date. We evaluated the association of periconceptional exposure to the Dutch Famine of 1944-45, as an example of an early environmental exposure, and single nucleotide polymorphisms covering the genetic variation (tagging SNPs) with DNA methylation at the imprinted IGF2/H19 region, a model for an epigenetically regulated genomic region. DNA methylation was measured at five differentially methylated regions (DMRs) that regulate the imprinted status of the IGF2/H19 region. Small but consistent differences in DNA methylation were observed comparing 60 individuals with periconceptional famine exposure with unexposed same-sex siblings at all IGF2 DMRs (PBH<0.05 after adjustment for multiple testing), but not at the H19 DMR. IGF2 DMR0 methylation was associated with IGF2 SNP rs2239681 (PBH = 0.027) and INS promoter methylation with INS SNPs, including rs689, which tags the INS VNTR, suggesting a mechanism for the reported effect of the VNTR on INS expression (PBH = 3.4×10-3). Prenatal famine and genetic variation showed similar associations with IGF2/H19 methylation and their contributions were additive. They were small in absolute terms (<3%), but on average 0.5 standard deviations relative to the variation in the population. Our analyses suggest that environmental and genetic factors could have independent and additive similarly sized effects on DNA methylation at the same regulatory site. [ABSTRACT FROM AUTHOR]

Published
2012
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48. Genome-Wide Study of Gene Variants Associated with Differential Cardiovascular Event Reduction by Pravastatin Therapy.

Author

Shiffman, Dov, Trompet, Stella, Louie, Judy Z., Rowland, Charles M., Catanese, Joseph J., Iakoubova, Olga A., Kirchgessner, Todd G., Westendorp, Rudi G. J., De Craen, Anton J. M., Eline Slagboom, P., Buckley, Brendan M., Stott, David J., Sattar, Naveed, Devlin, James J., Packard, Christopher J., Ford, Ian, Sacks, Frank M., and Wouter Jukema, J.

Subjects
PRAVASTATIN, GENOMES, CORONARY heart disease treatment, STATINS (Cardiovascular agents), PLACEBOS, GENOTYPE-environment interaction
Abstract

Statin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin. In a combined case-only analysis, 79 single nucleotide polymorphisms (SNPs) were associated with differential CHD event reduction by pravastatin according to genotype (P<0.0001), and these SNPs were analyzed in a second stage that included cases as well as non-cases from CARE and WOSCOPS and patients from the PROspective Study of Pravastatin in the Elderly at Risk/PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease (PROSPER/PHASE), a randomized placebo controlled study of pravastatin in the elderly. We found that one of these SNPs (rs13279522) was associated with differential CHD event reduction by pravastatin therapy in all 3 studies: P = 0.002 in CARE, P = 0.01 in WOSCOPS, P = 0.002 in PROSPER/PHASE. In a combined analysis of CARE, WOSCOPS, and PROSPER/PHASE, the hazard ratio for CHD when comparing pravastatin with placebo decreased by a factor of 0.63 (95% CI: 0.52 to 0.75) for each extra copy of the minor allele (P = 4.8×10-7). This SNP is located in DnaJ homolog subfamily C member 5B (DNAJC5B) and merits investigation in additional randomized studies of pravastatin and other statins. [ABSTRACT FROM AUTHOR]

Published
2012
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49. Mental Performance in Old Age Dependent on Cortisol and Genetic Variance in the Mineralocorticoid and Glucocorticoid Receptors.

Author

Kuningas, Maris, de Rijk, Roel H, Westendorp, Rudi G J, Jolles, Jelle, Eline Slagboom, P, and van Heemst, Diana

Subjects
COGNITION, MINERALOCORTICOIDS, GLUCOCORTICOID receptors, HYDROCORTISONE, GENETIC polymorphisms, NEUROPSYCHOPHARMACOLOGY
Abstract

Depression and cognitive decline have been associated with changes in circulating cortisol concentrations. Cortisol exerts its functions through mineralocorticoid (MR) and glucocorticoid (GR) receptors. However, data on the influence of variations in the MR and GR genes on depressive symptoms and cognitive functioning in older adults are scarce. Therefore, we explored the impact of MR-215G/C, MR-I180V, GR-ER22/23EK, GR-N363S, and GR-BclI polymorphisms on these end points in the population-based Leiden 85-plus Study. This prospective study includes 563 participants aged 85 years and older, with a mean follow-up of 4.2 years. In this study, high morning cortisol levels (per 1 SD cortisol) associated with impairments in global cognitive functioning (p=0.002) at baseline (age 85). These impairments were mainly attributable to lower attention (p=0.057) and slower processing speed (p=0.014). Similar effects were also observed during follow-up (age 85–90), where participants with higher cortisol levels (per 1 SD cortisol) had impaired global cognitive functioning (p=0.003), as well as impairments in attention (p=0.034) and processing speed (p=0.013). Changes in depressive symptoms were observed for the MR-I180V single-nucleotide polymorphism (SNP), where during follow-up the prevalence of depressive symptoms was higher in the 180V-allele carriers (p=0.049) compared to noncarriers. Dependent on these polymorphisms, no differences in overall and in specific domains of cognitive functioning were observed. In conclusion, the MR-I180V SNP has a specific effect on depressive symptoms, independent from cognitive functioning, and other polymorphisms in the MR and GR genes. In contrast, these genetic variants in the MR and GR genes do not influence cognitive functioning in old age.Neuropsychopharmacology (2007) 32, 1295–1301. doi:10.1038/sj.npp.1301260; published online 29 November 2006 [ABSTRACT FROM AUTHOR]

Published
2007
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50. Association between leptin, adiponectin and resistin and long-term progression of hand osteoarthritis.

Author

Yusuf, Erlangga, Ioan-Facsinay, Andreea, Bijsterbosch, Jessica, Klein-Wieringa, Inge, Kwekkeboom, Joanneke, Eline Slagboom, P., Huizinga, Tom W. J., and Kloppenburg, Margreet

Abstract

Objective To investigate the association between baseline serum adipokines levels—leptin, adiponectin and resistin—and long-term progression of hand osteoarthritis (HOA). Methods Baseline and 6-year radiographs of 164 patients (mean age 60 years, 81% women) with HOA (defined as a Kellgren and Lawrence score ⩾2 in at least two hand joints) were assessed for joint space narrowing (JSN) in 32 hand joints using the Osteoarthritis Research Society International atlas. Progression was defined as a change in the sum of the JSN score above the smallest detectable change of 2, reflecting change above measurement error. Serum adipokines were measured at baseline and patients were categorised by adipokine tertiles. RRs (and 95% CI) of HOA progression for patients in the second and third tertiles were calculated relative to the first tertile, using generalised estimating equations. Adjustments were made for age, sex and body mass index. Results Patients in the two highest tertiles of adiponectin had a decreased risk of 70% (RR=0.3 (0.2 to 0.7)) for HOA progression in comparison with patients in the lowest tertile. Leptin and resistin levels were not associated with progression. Conclusion Adiponectin levels are associated with progression of HOA, suggesting that adiponectin may be involved in the pathophysiology of OA. [ABSTRACT FROM AUTHOR]

Published
2011
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