3,037 results on '"Rivadeneira, Fernando"'
Search Results
2. Author Correction: LINE-1 RNA triggers matrix formation in bone cells via a PKR-mediated inflammatory response
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Mangiavacchi, Arianna, Morelli, Gabriele, Reppe, Sjur, Saera-Vila, Alfonso, Liu, Peng, Eggerschwiler, Benjamin, Zhang, Huoming, Bensaddek, Dalila, Casanova, Elisa A, Medina Gomez, Carolina, Prijatelj, Vid, Della Valle, Francesco, Atinbayeva, Nazerke, Izpisua Belmonte, Juan Carlos, Rivadeneira, Fernando, Cinelli, Paolo, Gautvik, Kaare Morten, and Orlando, Valerio
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- 2024
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3. Facilitators and constraints of physical activity in adults with achondroplasia: a scoping review
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Alves, Inês, Koromani, Fjorda, Lemos, Carolina, Tavares, Sofia, Fernandes, Orlando, Pereira, Cidália D., Castro, Maria António, and Rivadeneira, Fernando
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- 2024
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4. Author Correction: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes
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Bradfeld, Jonathan P., Kember, Rachel L., Ulrich, Anna, Balkhiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M., Bell, Joshua A., Broadaway, K. Alaine, Chen, Zhanghua, Chai, Jin-Fang, Davies, Neil M., Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke-Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M., Have, Christian Theil, Strachan, David P., Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H., Wang, Carol A., Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithiof-Bøjsøe, Christine, Gauderman, W. James, Glessner, Joseph T., Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L., Kaakinen, Marika, Kalkwarf, Heidi, Kelly, Andrea, Kindler, Joseph, Kähönen, Mika, Lanca, Carla, Lappe, Joan, Lee, Nanette R., McCormack, Shana, Mentch, Frank D., Mitchell, Jonathan A., Mononen, Nina, Niinikoski, Harri, Oken, Emily, Pahkala, Katja, Sim, Xueling, Teo, Yik-Ying, Baier, Leslie J., van Beijsterveldt, Toos, Adair, Linda S., Boomsma, Dorret I., de Geus, Eco, Guxens, Mònica, Eriksson, Johan G., Felix, Janine F., Gilliland, Frank D., Hansen, Torben, Hardy, Rebecca, Hivert, Marie-France, Holm, Jens-Christian, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Lehtimäki, Terho, Mackey, David A., Meyre, David, Mohlke, Karen L., Mykkänen, Juha, Oberfeld, Sharon, Pennell, Craig E., Perry, John R. B., Raitakari, Olli, Rivadeneira, Fernando, Saw, Seang-Mei, Sebert, Sylvain, Shepherd, John A., Standl, Marie, Sørensen, Thorkild I. A., Timpson, Nicholas J., Torrent, Maties, Willemsen, Gonneke, Hypponen, Elina, Power, Chris, McCarthy, Mark I., Freathy, Rachel M., Widén, Elisabeth, Hakonarson, Hakon, Prokopenko, Inga, Voight, Benjamin F., Zemel, Babette S., Grant, Struan F. A., and Cousminer, Diana L.
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- 2024
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5. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes
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Bradfield, Jonathan P., Kember, Rachel L., Ulrich, Anna, Balkhiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M., Bell, Joshua A., Broadaway, K. Alaine, Chen, Zhanghua, Chai, Jin-Fang, Davies, Neil M., Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke-Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M., Have, Christian Theil, Strachan, David P., Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H., Wang, Carol A., Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithioff-Bøjsøe, Christine, Gauderman, W. James, Glessner, Joseph T., Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L., Kaakinen, Marika, Kalkwarf, Heidi, Kelly, Andrea, Kindler, Joseph, Kähönen, Mika, Lanca, Carla, Lappe, Joan, Lee, Nanette R., McCormack, Shana, Mentch, Frank D., Mitchell, Jonathan A., Mononen, Nina, Niinikoski, Harri, Oken, Emily, Pahkala, Katja, Sim, Xueling, Teo, Yik-Ying, Baier, Leslie J., van Beijsterveldt, Toos, Adair, Linda S., Boomsma, Dorret I., de Geus, Eco, Guxens, Mònica, Eriksson, Johan G., Felix, Janine F., Gilliland, Frank D., Biobank, Penn Medicine, Hansen, Torben, Hardy, Rebecca, Hivert, Marie-France, Holm, Jens-Christian, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Lehtimäki, Terho, Mackey, David A., Meyre, David, Mohlke, Karen L., Mykkänen, Juha, Oberfield, Sharon, Pennell, Craig E., Perry, John R. B., Raitakari, Olli, Rivadeneira, Fernando, Saw, Seang-Mei, Sebert, Sylvain, Shepherd, John A., Standl, Marie, Sørensen, Thorkild I. A., Timpson, Nicholas J., Torrent, Maties, Willemsen, Gonneke, Hypponen, Elina, Power, Chris, McCarthy, Mark I., Freathy, Rachel M., Widén, Elisabeth, Hakonarson, Hakon, Prokopenko, Inga, Voight, Benjamin F., Zemel, Babette S., Grant, Struan F. A., and Cousminer, Diana L.
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- 2024
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6. Defining type 2 diabetes polygenic risk scores through colocalization and network-based clustering of metabolic trait genetic associations
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Ghatan, Samuel, van Rooij, Jeroen, van Hoek, Mandy, Boer, Cindy G., Felix, Janine F., Kavousi, Maryam, Jaddoe, Vincent W., Sijbrands, Eric J. G., Medina-Gomez, Carolina, Rivadeneira, Fernando, and Oei, Ling
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- 2024
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7. A meta-analysis of previous falls and subsequent fracture risk in cohort studies
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Vandenput, Liesbeth, Johansson, Helena, McCloskey, Eugene V., Liu, Enwu, Schini, Marian, Åkesson, Kristina E., Anderson, Fred A., Azagra, Rafael, Bager, Cecilie L., Beaudart, Charlotte, Bischoff-Ferrari, Heike A., Biver, Emmanuel, Bruyère, Olivier, Cauley, Jane A., Center, Jacqueline R., Chapurlat, Roland, Christiansen, Claus, Cooper, Cyrus, Crandall, Carolyn J., Cummings, Steven R., da Silva, José A. P., Dawson-Hughes, Bess, Diez-Perez, Adolfo, Dufour, Alyssa B., Eisman, John A., Elders, Petra J. M., Ferrari, Serge, Fujita, Yuki, Fujiwara, Saeko, Glüer, Claus-Christian, Goldshtein, Inbal, Goltzman, David, Gudnason, Vilmundur, Hall, Jill, Hans, Didier, Hoff, Mari, Hollick, Rosemary J., Huisman, Martijn, Iki, Masayuki, Ish-Shalom, Sophia, Jones, Graeme, Karlsson, Magnus K., Khosla, Sundeep, Kiel, Douglas P., Koh, Woon-Puay, Koromani, Fjorda, Kotowicz, Mark A., Kröger, Heikki, Kwok, Timothy, Lamy, Olivier, Langhammer, Arnulf, Larijani, Bagher, Lippuner, Kurt, McGuigan, Fiona E. A., Mellström, Dan, Merlijn, Thomas, Nguyen, Tuan V., Nordström, Anna, Nordström, Peter, O’Neill, Terence W., Obermayer-Pietsch, Barbara, Ohlsson, Claes, Orwoll, Eric S., Pasco, Julie A., Rivadeneira, Fernando, Schott, Anne-Marie, Shiroma, Eric J., Siggeirsdottir, Kristin, Simonsick, Eleanor M., Sornay-Rendu, Elisabeth, Sund, Reijo, Swart, Karin M. A., Szulc, Pawel, Tamaki, Junko, Torgerson, David J., van Schoor, Natasja M., van Staa, Tjeerd P., Vila, Joan, Wareham, Nicholas J., Wright, Nicole C., Yoshimura, Noriko, Zillikens, MCarola, Zwart, Marta, Harvey, Nicholas C., Lorentzon, Mattias, Leslie, William D., and Kanis, John A.
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- 2024
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8. The Rotterdam Study. Design update and major findings between 2020 and 2024
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Ikram, M. Arfan, Kieboom, Brenda C.T., Brouwer, Willem Pieter, Brusselle, Guy, Chaker, Layal, Ghanbari, Mohsen, Goedegebure, André, Ikram, M. Kamran, Kavousi, Maryam, de Knegt, Rob J., Luik, Annemarie I., van Meurs, Joyce, Pardo, Luba M., Rivadeneira, Fernando, van Rooij, Frank J.A., Vernooij, Meike W., Voortman, Trudy, and Terzikhan, Natalie
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- 2024
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9. Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth
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Beaumont, Robin N., Flatley, Christopher, Vaudel, Marc, Wu, Xiaoping, Chen, Jing, Moen, Gunn-Helen, Skotte, Line, Helgeland, Øyvind, Solé-Navais, Pol, Banasik, Karina, Albiñana, Clara, Ronkainen, Justiina, Fadista, João, Stinson, Sara Elizabeth, Trajanoska, Katerina, Wang, Carol A., Westergaard, David, Srinivasan, Sundararajan, Sánchez-Soriano, Carlos, Bilbao, Jose Ramon, Allard, Catherine, Groleau, Marika, Kuulasmaa, Teemu, Leirer, Daniel J., White, Frédérique, Jacques, Pierre-Étienne, Cheng, Haoxiang, Hao, Ke, Andreassen, Ole A., Åsvold, Bjørn Olav, Atalay, Mustafa, Bhatta, Laxmi, Bouchard, Luigi, Brumpton, Ben Michael, Brunak, Søren, Bybjerg-Grauholm, Jonas, Ebbing, Cathrine, Elliott, Paul, Engelbrechtsen, Line, Erikstrup, Christian, Estarlich, Marisa, Franks, Stephen, Gaillard, Romy, Geller, Frank, Grove, Jakob, Hougaard, David M., Kajantie, Eero, Morgen, Camilla S., Nohr, Ellen A., Nyegaard, Mette, Palmer, Colin N. A., Pedersen, Ole Birger, Rivadeneira, Fernando, Sebert, Sylvain, Shields, Beverley M., Stoltenberg, Camilla, Surakka, Ida, Thørner, Lise Wegner, Ullum, Henrik, Vaarasmaki, Marja, Vilhjalmsson, Bjarni J., Willer, Cristen J., Lakka, Timo A., Gybel-Brask, Dorte, Bustamante, Mariona, Hansen, Torben, Pearson, Ewan R., Reynolds, Rebecca M., Ostrowski, Sisse R., Pennell, Craig E., Jaddoe, Vincent W. V., Felix, Janine F., Hattersley, Andrew T., Melbye, Mads, Lawlor, Deborah A., Hveem, Kristian, Werge, Thomas, Nielsen, Henriette Svarre, Magnus, Per, Evans, David M., Jacobsson, Bo, Järvelin, Marjo-Riitta, Zhang, Ge, Hivert, Marie-France, Johansson, Stefan, Freathy, Rachel M., Feenstra, Bjarke, and Njølstad, Pål R.
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- 2023
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10. Whole-exome sequence analysis of anthropometric traits illustrates challenges in identifying effects of rare genetic variants
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Young, Kristin L, Fisher, Virginia, Deng, Xuan, Brody, Jennifer A, Graff, Misa, Lim, Elise, Lin, Bridget M, Xu, Hanfei, Amin, Najaf, An, Ping, Aslibekyan, Stella, Fohner, Alison E, Hidalgo, Bertha, Lenzini, Petra, Kraaij, Robert, Medina-Gomez, Carolina, Prokić, Ivana, Rivadeneira, Fernando, Sitlani, Colleen, Tao, Ran, van Rooij, Jeroen, Zhang, Di, Broome, Jai G, Buth, Erin J, Heavner, Benjamin D, Jain, Deepti, Smith, Albert V, Barnes, Kathleen, Boorgula, Meher Preethi, Chavan, Sameer, Darbar, Dawood, De Andrade, Mariza, Guo, Xiuqing, Haessler, Jeffrey, Irvin, Marguerite R, Kalyani, Rita R, Kardia, Sharon LR, Kooperberg, Charles, Kim, Wonji, Mathias, Rasika A, McDonald, Merry-Lynn, Mitchell, Braxton D, Peyser, Patricia A, Regan, Elizabeth A, Redline, Susan, Reiner, Alexander P, Rich, Stephen S, Rotter, Jerome I, Smith, Jennifer A, Weiss, Scott, Wiggins, Kerri L, Yanek, Lisa R, Arnett, Donna, Heard-Costa, Nancy L, Leal, Suzanne, Lin, Danyu, McKnight, Barbara, Province, Michael, van Duijn, Cornelia M, North, Kari E, Cupples, L Adrienne, and Liu, Ching-Ti
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Biological Sciences ,Genetics ,Clinical Research ,Biotechnology ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Generic health relevance ,Good Health and Well Being ,Humans ,Genome-Wide Association Study ,Exome ,Body Mass Index ,Quantitative Trait Loci ,Anthropometry ,Intercellular Signaling Peptides and Proteins ,Cell Cycle Proteins ,body mass index ,central obesity ,exome sequencing ,height - Abstract
Anthropometric traits, measuring body size and shape, are highly heritable and significant clinical risk factors for cardiometabolic disorders. These traits have been extensively studied in genome-wide association studies (GWASs), with hundreds of genome-wide significant loci identified. We performed a whole-exome sequence analysis of the genetics of height, body mass index (BMI) and waist/hip ratio (WHR). We meta-analyzed single-variant and gene-based associations of whole-exome sequence variation with height, BMI, and WHR in up to 22,004 individuals, and we assessed replication of our findings in up to 16,418 individuals from 10 independent cohorts from Trans-Omics for Precision Medicine (TOPMed). We identified four trait associations with single-nucleotide variants (SNVs; two for height and two for BMI) and replicated the LECT2 gene association with height. Our expression quantitative trait locus (eQTL) analysis within previously reported GWAS loci implicated CEP63 and RFT1 as potential functional genes for known height loci. We further assessed enrichment of SNVs, which were monogenic or syndromic variants within loci associated with our three traits. This led to the significant enrichment results for height, whereas we observed no Bonferroni-corrected significance for all SNVs. With a sample size of ∼20,000 whole-exome sequences in our discovery dataset, our findings demonstrate the importance of genomic sequencing in genetic association studies, yet they also illustrate the challenges in identifying effects of rare genetic variants.
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- 2023
11. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease
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Holstege, Henne, Hulsman, Marc, Charbonnier, Camille, Grenier-Boley, Benjamin, Quenez, Olivier, Grozeva, Detelina, van Rooij, Jeroen GJ, Sims, Rebecca, Ahmad, Shahzad, Amin, Najaf, Norsworthy, Penny J, Dols-Icardo, Oriol, Hummerich, Holger, Kawalia, Amit, Amouyel, Philippe, Beecham, Gary W, Berr, Claudine, Bis, Joshua C, Boland, Anne, Bossù, Paola, Bouwman, Femke, Bras, Jose, Campion, Dominique, Cochran, J Nicholas, Daniele, Antonio, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Denning, Nicola, DeStefano, Anita L, Farrer, Lindsay A, Fernández, Maria Victoria, Fox, Nick C, Galimberti, Daniela, Genin, Emmanuelle, Gille, Johan JP, Le Guen, Yann, Guerreiro, Rita, Haines, Jonathan L, Holmes, Clive, Ikram, M Arfan, Ikram, M Kamran, Jansen, Iris E, Kraaij, Robert, Lathrop, Marc, Lemstra, Afina W, Lleó, Alberto, Luckcuck, Lauren, Mannens, Marcel MAM, Marshall, Rachel, Martin, Eden R, Masullo, Carlo, Mayeux, Richard, Mecocci, Patrizia, Meggy, Alun, Mol, Merel O, Morgan, Kevin, Myers, Richard M, Nacmias, Benedetta, Naj, Adam C, Napolioni, Valerio, Pasquier, Florence, Pastor, Pau, Pericak-Vance, Margaret A, Raybould, Rachel, Redon, Richard, Reinders, Marcel JT, Richard, Anne-Claire, Riedel-Heller, Steffi G, Rivadeneira, Fernando, Rousseau, Stéphane, Ryan, Natalie S, Saad, Salha, Sanchez-Juan, Pascual, Schellenberg, Gerard D, Scheltens, Philip, Schott, Jonathan M, Seripa, Davide, Seshadri, Sudha, Sie, Daoud, Sistermans, Erik A, Sorbi, Sandro, van Spaendonk, Resie, Spalletta, Gianfranco, Tesi, Niccolo’, Tijms, Betty, Uitterlinden, André G, van der Lee, Sven J, Visser, Pieter Jelle, Wagner, Michael, Wallon, David, Wang, Li-San, Zarea, Aline, Clarimon, Jordi, van Swieten, John C, Greicius, Michael D, Yokoyama, Jennifer S, Cruchaga, Carlos, Hardy, John, and Ramirez, Alfredo
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Biological Sciences ,Genetics ,Dementia ,Alzheimer's Disease ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Human Genome ,Prevention ,Acquired Cognitive Impairment ,Neurodegenerative ,Aging ,Clinical Research ,Biotechnology ,Brain Disorders ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Humans ,Adenosine Triphosphatases ,Alzheimer Disease ,ATP Binding Cassette Transporter 1 ,Genome-Wide Association Study ,Risk Factors ,Exosomes ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.
- Published
- 2022
12. List of contributors
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Adams, John S., primary, Amrein, Karin, additional, Anderson, Paul H., additional, Arnold, Leggy A., additional, Arora, Juhi, additional, Artusa, Patricio, additional, Ascherio, Alberto, additional, Asmussen, Niels C., additional, Astier, Anne L., additional, Bak, Min Ji, additional, Bauerle, Kevin T., additional, Belorusova, Anna Y., additional, Benkusky, Nancy A., additional, Bernal-Mizrachi, Carlos, additional, Bhattoa, Harjit P., additional, Bikle, Daniel D., additional, Bilezikian, John P., additional, Binkley, Neil C., additional, Bischoff-Ferrari, Heike A., additional, Bishop, Charles W., additional, Blomberg Jensen, Martin, additional, Boisen, Ida Marie, additional, Boucher, Barbara J., additional, Bouillon, Roger, additional, Boyan, Barbara D., additional, Bradford, Dana, additional, Brancatella, Alessandro, additional, Buburuzan, Laura, additional, Burne, Thomas H.J., additional, Buschittari, Damien, additional, Calkins, Hannah, additional, Calvo, Mona S., additional, Camargo, Carlos A., additional, Campbell, Moray J., additional, Cantorna, Margherita T., additional, Cappellani, Daniele, additional, Carlberg, Carsten, additional, Carmeliet, Geert, additional, Cashman, Kevin D., additional, Ceglia, Lisa, additional, Cetani, Filomena, additional, Chang, Wenhan, additional, Cheadle, Charlotte, additional, Chou, Sharon H., additional, Christakos, Sylvia, additional, Christopher, Kenneth B., additional, Chu, Emily Y., additional, Chun, Rene F., additional, Cleal, Jane K., additional, Cobice, Diego F., additional, Cooper, Cyrus, additional, Coort, Susan L.M., additional, Cui, Xiaoying, additional, Curtis, Elizabeth M., additional, Danilenko, Michael, additional, Darling, Andrea L., additional, David Roodman, G., additional, Dawson-Hughes, Bess, additional, de Jongh, Renate, additional, Demay, Marie B., additional, Dennison, Elaine M., additional, Dixon, Katie M., additional, Dong, Bingning, additional, Doroudi, Maryam, additional, Dusso, Adriana, additional, Dvorzhinskiy, Aleksey, additional, Ebeling, Peter R., additional, Erben, Reinhold G., additional, Evelo, Chris T.A., additional, Eyles, Darryl, additional, Feldman, David, additional, Ferrer-Mayorga, Gemma, additional, Fleet, James C., additional, Forcellati, Marianela, additional, Foster, Brian L., additional, Gafni, Rachel I., additional, Gayan-Ramirez, Ghislaine, additional, Giovannucci, Edward, additional, Girgis, Christian M., additional, Glencross, Drew A., additional, Glorieux, Francis H., additional, Gocek, Elzbieta, additional, Goldfarb, David S., additional, Goltzman, David, additional, González-Sancho, José Manuel, additional, Grant, William B., additional, Groves, Natalie J., additional, Gysemans, Conny, additional, Harrison, Stephanie, additional, Harvey, Nicholas C., additional, Haseltine, Katherine, additional, Hawrylowicz, Catherine M., additional, Hayes, Colleen E., additional, Heckel, John E., additional, Hershberger, Pamela A., additional, Hewison, Martin, additional, Högler, Wolfgang, additional, Holick, Michael F., additional, Hollis, Bruce W., additional, Holt, Rune, additional, Hujoel, Philippe P., additional, Hyppönen, Elina, additional, Ismailova, Aiten, additional, Jablonski, Nina G., additional, Jakobsen, Jette, additional, Janssens, Wim, additional, Jeffery, Louisa, additional, Jenkinson, Carl, additional, Jensen, Marie Bagge, additional, Jetten, Anton M., additional, Jiang, Heng, additional, Johnson, Candace S., additional, Jones, Glenville, additional, Jones, Kerry S., additional, Jüppner, Harald, additional, Kalia, Vandana, additional, Kallay, Enikö, additional, Karapalis, Andrew C., additional, Kaufmann, Martin, additional, Kiely, Mairead, additional, Kim, Hanseul, additional, Kim, Tiffany Y., additional, Kojima, Hiroyuki, additional, Kooij, Ireen, additional, Kovacs, Christopher S., additional, Kremer, Richard, additional, Krieger, Kirsten, additional, Kritmetapak, Kittrawee, additional, Krueger, Diane C., additional, Kumar, Rajiv, additional, Kurihara, Noriyoshi, additional, Lane, Joseph M., additional, Lanham-New, Susan A., additional, Latic, Nejla, additional, LeBoff, Meryl S., additional, Lee, Maija B., additional, Lee, Seong Min, additional, Levine, Michael A., additional, Lewis, Richard, additional, Lewis, Rohan M., additional, Li, Wei, additional, Li, Yan Chun, additional, Lincoln, Matthew R., additional, Lips, Paul, additional, Lisse, Thomas S., additional, Liu, Eva S., additional, López de Maturana, Evangelina, additional, Lugg, Sebastian T., additional, Machado, Christopher J., additional, Maes, Karen, additional, Maestro, Miguel A., additional, Malats, Núria, additional, Malloy, Peter J., additional, Manousaki, Despoina, additional, Marcinkowska, Ewa, additional, Marcocci, Claudio, additional, Martens, Pieter-Jan, additional, Martineau, Adrian R., additional, Mason, Rebecca S., additional, Mathieu, Chantal, additional, Mayne, Phoebe, additional, McGrath, John J., additional, Mehta, Mansi, additional, Mellanby, Richard John, additional, Merchant, Nadia, additional, Meyer, Mark B., additional, Miao, Dengshun, additional, Moon, Rebecca J., additional, Mortensen, Li Juel, additional, Motlaghzadeh, Yasaman, additional, Munger, Kassandra L., additional, Muñoz, Alberto, additional, Nakamichi, Yuko, additional, Narvaez, Carmen J., additional, Nikiphorou, Elena, additional, Nonn, Larisa, additional, Pal, Lubna, additional, Parekh, Dhruv, additional, Pettifor, John M., additional, Pike, J. Wesley, additional, Pilz, Stefan, additional, Pittas, Anastassios G., additional, Pludowski, Pawel, additional, Prosser, David E., additional, Pullagura, Sri Ramulu N., additional, Raphael, Joseph, additional, Rauz, Saaeha, additional, Raza, Karim, additional, Real, Francisco X., additional, Reichrath, Jörg, additional, Richards, J. Brent, additional, Rivadeneira, Fernando, additional, Rochel, Natacha, additional, Roizen, Jeffrey D., additional, Ryan, Brittany A., additional, Sarkar, Surojit, additional, Sarmadi, Fatemeh, additional, Schafer, Anne L., additional, Schepelmann, Martin, additional, Schoenmakers, Inez, additional, Schuit, Frans, additional, Schwartz, Zvi, additional, Scott, Kayla M., additional, Sellmeyer, Deborah E., additional, Sempos, Christopher T., additional, Sepiashvili, Lusia, additional, Seshadri, Mukund, additional, Shane, Elizabeth, additional, Shaurova, Tatiana, additional, Shieh, Albert, additional, Shui, Irene, additional, Singh, Ravinder J., additional, Slominski, Andrzej T., additional, Smith, Karl W., additional, St-Arnaud, René, additional, Stein, Emily M., additional, Studzinski, George P., additional, Suda, Tatsuo, additional, Takahashi, Naoyuki, additional, Taylor, Hugh S., additional, Tebben, Peter J., additional, Thacher, Tom D., additional, Thandrayen, Kebashni, additional, Thickett, David R., additional, Tiosano, Dov, additional, Trajanoska, Katerina, additional, Tu, Chia-Ling, additional, Tuckey, Robert C., additional, Tutaworn, Teerapat, additional, Udagawa, Nobuyuki, additional, Uday, Suma, additional, Unnanuntana, Aasis, additional, van Driel, Marjolein, additional, van Leeuwen, Johannes P.T.M., additional, van Schoor, Natasja, additional, Verlinden, Lieve, additional, Vieth, Reinhold, additional, Vimaleswaran, Karina S., additional, Wagner, Carol L., additional, Wallace, Graham R., additional, Weaver, Connie M., additional, Webb, Daniel A., additional, Welsh, JoEllen, additional, White, John H., additional, Whiting, Susan J., additional, Williams, Emma L., additional, Yahyavi, Sam Kafai, additional, Yamamoto, Keiko, additional, Yates, Clayton, additional, Zagorac, Sladjana, additional, Zhang, Rong Mei, additional, Zhao, Hengguang, additional, Zhou, Ang, additional, and Zittermann, Armin, additional
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- 2024
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13. Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
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Jami, Eshim S, Hammerschlag, Anke R, Ip, Hill F, Allegrini, Andrea G, Benyamin, Beben, Border, Richard, Diemer, Elizabeth W, Jiang, Chang, Karhunen, Ville, Lu, Yi, Lu, Qing, Mallard, Travis T, Mishra, Pashupati P, Nolte, Ilja M, Palviainen, Teemu, Peterson, Roseann E, Sallis, Hannah M, Shabalin, Andrey A, Tate, Ashley E, Thiering, Elisabeth, Vilor-Tejedor, Natàlia, Wang, Carol, Zhou, Ang, Adkins, Daniel E, Alemany, Silvia, Ask, Helga, Chen, Qi, Corley, Robin P, Ehli, Erik A, Evans, Luke M, Havdahl, Alexandra, Hagenbeek, Fiona A, Hakulinen, Christian, Henders, Anjali K, Hottenga, Jouke Jan, Korhonen, Tellervo, Mamun, Abdullah, Marrington, Shelby, Neumann, Alexander, Rimfeld, Kaili, Rivadeneira, Fernando, Silberg, Judy L, van Beijsterveldt, Catharina E, Vuoksimaa, Eero, Whipp, Alyce M, Tong, Xiaoran, Andreassen, Ole A, Boomsma, Dorret I, Brown, Sandra A, Burt, S Alexandra, Copeland, William, Dick, Danielle M, Harden, K Paige, Harris, Kathleen Mullan, Hartman, Catharina A, Heinrich, Joachim, Hewitt, John K, Hopfer, Christian, Hypponen, Elina, Jarvelin, Marjo-Riitta, Kaprio, Jaakko, Keltikangas-Järvinen, Liisa, Klump, Kelly L, Krauter, Kenneth, Kuja-Halkola, Ralf, Larsson, Henrik, Lehtimäki, Terho, Lichtenstein, Paul, Lundström, Sebastian, Maes, Hermine H, Magnus, Per, Munafò, Marcus R, Najman, Jake M, Njølstad, Pål R, Oldehinkel, Albertine J, Pennell, Craig E, Plomin, Robert, Reichborn-Kjennerud, Ted, Reynolds, Chandra, Rose, Richard J, Smolen, Andrew, Snieder, Harold, Stallings, Michael, Standl, Marie, Sunyer, Jordi, Tiemeier, Henning, Wadsworth, Sally J, Wall, Tamara L, Whitehouse, Andrew JO, Williams, Gail M, Ystrøm, Eivind, Nivard, Michel G, Bartels, Meike, and Middeldorp, Christel M
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Biological Psychology ,Psychology ,Serious Mental Illness ,Brain Disorders ,Pediatric ,Human Genome ,Genetics ,Behavioral and Social Science ,Depression ,Mental Health ,Mental Illness ,2.1 Biological and endogenous factors ,2.3 Psychological ,social and economic factors ,Mental health ,Adolescent ,Adult ,Aggression ,Anxiety ,Attention Deficit Disorder with Hyperactivity ,Autistic Disorder ,Bipolar Disorder ,Child ,Child ,Preschool ,Genome-Wide Association Study ,Humans ,Loneliness ,Polymorphism ,Single Nucleotide ,Schizophrenia ,Sleep Initiation and Maintenance Disorders ,depression ,anxiety ,repeated measures ,genetic epidemiology ,molecular genetics ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Developmental & Child Psychology ,Clinical sciences ,Paediatrics ,Applied and developmental psychology - Abstract
ObjectiveTo investigate the genetic architecture of internalizing symptoms in childhood and adolescence.MethodIn 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.ResultsThe meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa.ConclusionGenetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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- 2022
14. A perspective on muscle phenotyping in musculoskeletal research
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Foessl, Ines, Ackert-Bicknell, Cheryl L., Kague, Erika, Laskou, Faidra, Jakob, Franz, Karasik, David, Obermayer-Pietsch, Barbara, Alonso, Nerea, Bjørnerem, Åshild, Brandi, Maria Luisa, Busse, Björn, Calado, Ângelo, Cebi, Alper Han, Christou, Maria, Curran, Kathleen M., Hald, Jannie Dahl, Semeraro, Maria Donatella, Douni, Eleni, Duncan, Emma L., Duran, Ivan, Formosa, Melissa M., Gabet, Yankel, Ghatan, Samuel, Gkitakou, Artemis, Hassler, Eva Maria, Högler, Wolfgang, Heino, Terhi J., Hendrickx, Gretl, Khashayar, Patricia, Kiel, Douglas P., Koromani, Fjorda, Langdahl, Bente, Lopes, Philippe, Mäkitie, Outi, Maurizi, Antonio, Medina-Gomez, Carolina, Ntzani, Evangelia, Ohlsson, Claes, Prijatelj, Vid, Rabionet, Raquel, Reppe, Sjur, Rivadeneira, Fernando, Roshchupkin, Gennady, Sharma, Neha, Søe, Kent, Styrkarsdottir, Unnur, Szulc, Pavel, Teti, Anna, Tobias, Jon, Valjevac, Amina, van de Peppel, Jeroen, van der Eerden, Bram, van Rietbergen, Bert, Zekic, Tatjana, and Zillikens, M. Carola
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- 2024
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15. Bone health index in the assessment of bone health: The Generation R Study
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Prijatelj, Vid, Grgic, Olja, Uitterlinden, André G., Wolvius, Eppo B., Rivadeneira, Fernando, and Medina-Gomez, Carolina
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- 2024
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16. Oral microbiota of adolescents with dental caries: A systematic review
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Veenman, Francien, van Dijk, Anne, Arredondo, Alexandre, Medina-Gomez, Carolina, Wolvius, Eppo, Rivadeneira, Fernando, Àlvarez, Gerard, Blanc, Vanessa, and Kragt, Lea
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- 2024
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17. Early-life stress and the gut microbiome: A comprehensive population-based investigation
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Mulder, Rosa H., Kraaij, Robert, Schuurmans, Isabel K., Frances-Cuesta, Carlos, Sanz, Yolanda, Medina-Gomez, Carolina, Duijts, Liesbeth, Rivadeneira, Fernando, Tiemeier, Henning, Jaddoe, Vincent W.V., Felix, Janine F., and Cecil, Charlotte A.M.
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- 2024
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18. Oral and craniofacial research in the Generation R study: an executive summary
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van Meijeren-van Lunteren, Agatha W., Liu, Xianjing, Veenman, Francien C. H., Grgic, Olja, Dhamo, Brunilda, van der Tas, Justin T., Prijatelj, Vid, Roshchupkin, Gennady V., Rivadeneira, Fernando, Wolvius, Eppo B., and Kragt, Lea
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- 2023
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19. Genomic analysis of diet composition finds novel loci and associations with health and lifestyle
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Meddens, S Fleur W, de Vlaming, Ronald, Bowers, Peter, Burik, Casper AP, Linnér, Richard Karlsson, Lee, Chanwook, Okbay, Aysu, Turley, Patrick, Rietveld, Cornelius A, Fontana, Mark Alan, Ghanbari, Mohsen, Imamura, Fumiaki, McMahon, George, van der Most, Peter J, Voortman, Trudy, Wade, Kaitlin H, Anderson, Emma L, Braun, Kim VE, Emmett, Pauline M, Esko, Tonũ, Gonzalez, Juan R, Kiefte-de Jong, Jessica C, Langenberg, Claudia, Luan, Jian’an, Muka, Taulant, Ring, Susan, Rivadeneira, Fernando, Snieder, Harold, van Rooij, Frank JA, Wolffenbuttel, Bruce HR, Smith, George Davey, Franco, Oscar H, Forouhi, Nita G, Ikram, M Arfan, Uitterlinden, Andre G, van Vliet-Ostaptchouk, Jana V, Wareham, Nick J, Cesarini, David, Harden, K Paige, Lee, James J, Benjamin, Daniel J, Chow, Carson C, and Koellinger, Philipp D
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Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Prevention ,Behavioral and Social Science ,Genetics ,Obesity ,Human Genome ,Nutrition ,Diabetes ,Aetiology ,2.1 Biological and endogenous factors ,Cardiovascular ,Metabolic and endocrine ,Body Mass Index ,Diabetes Mellitus ,Type 2 ,Diet ,Genome-Wide Association Study ,Genomics ,Humans ,Life Style ,23andMe Research Team ,EPIC- InterAct Consortium ,Lifelines Cohort Study ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Biological psychology ,Clinical and health psychology - Abstract
We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P
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- 2021
20. Large-scale association analyses identify host factors influencing human gut microbiome composition
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Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I, Raygoza Garay, Juan Antonio, Finnicum, Casey T, Liu, Xingrong, Zhernakova, Daria V, Bonder, Marc Jan, Hansen, Tue H, Frost, Fabian, Rühlemann, Malte C, Turpin, Williams, Moon, Jee-Young, Kim, Han-Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A, Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D, Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T, Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I, Burk, Robert D, Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E, van Duijn, Cornelia M, Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A, Ijzerman, Richard G, Jackson, Matthew A, Jaddoe, Vincent WV, Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J, Lieb, Wolfgang, Lusis, Aldons J, Masclee, Ad AM, Moll, Henriette A, Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J, Steves, Claire J, Thorsen, Jonathan, Timpson, Nicholas J, Tito, Raul Y, Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H, Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U, Weissbrod, Omer, Westra, Harm-Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy MAE, Arias Vasquez, Alejandro, de Geus, Eco JC, Meyer, Katie A, Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung-Lae, Kaplan, Robert C, Spector, Tim D, Uitterlinden, Andre G, Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M, Franke, Lude, Sanna, Serena, D’Amato, Mauro, and Pedersen, Oluf
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Microbiology ,Biological Sciences ,Genetics ,Human Genome ,Biotechnology ,Clinical Research ,Digestive Diseases ,Nutrition ,2.1 Biological and endogenous factors ,Aetiology ,Oral and gastrointestinal ,Adolescent ,Adult ,Bifidobacterium ,Child ,Child ,Preschool ,Cohort Studies ,Female ,Gastrointestinal Microbiome ,Genetic Variation ,Genome-Wide Association Study ,Humans ,Lactase ,Linkage Disequilibrium ,Male ,Mendelian Randomization Analysis ,Metabolism ,Quantitative Trait Loci ,RNA ,Ribosomal ,16S ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P
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- 2021
21. Genome-wide association study identifies 48 common genetic variants associated with handedness
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Cuellar-Partida, Gabriel, Tung, Joyce Y, Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A, Barroso, Inês, Beckmann, Jacques S, Boks, Marco P, Boomsma, Dorret I, Boyd, Heather A, Breteler, Monique MB, Campbell, Harry, Chasman, Daniel I, Cherkas, Lynn F, Davies, Gail, de Geus, Eco JC, Deary, Ian J, Deloukas, Panos, Dick, Danielle M, Duffy, David L, Eriksson, Johan G, Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D, Han, Jiali, Hansen, Thomas F, Hartmann, Annette M, Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A, Hirschhorn, Joel N, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Liang-Dar, Ikram, M Arfan, Kaprio, Jaakko, Kemp, John P, Khaw, Kay-Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth JF, Luciano, Michelle, Magnusson, Sigurdur H, Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G, McArdle, Wendy L, McCarthy, Mark I, Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A, Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R, O’Connell, Kevin S, Ophoff, Roel A, Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda WJH, Polasek, Ozren, Pramstaller, Peter P, Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H, Smith, George Davey, Smoller, Jordan W, Soranzo, Nicole, Spector, Tim D, Pourcain, Beate St, Starr, John M, Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J, Uitterlinden, André G, van Duijn, Cornelia M, van Rooij, Frank JA, Vink, Jaqueline M, Vollenweider, Peter, Vuoksimaa, Eero, and Waeber, Gérard
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Biological Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Psychology ,Human Genome ,Mental Health ,Brain Disorders ,Neurosciences ,Schizophrenia ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Adult ,Aged ,Female ,Functional Laterality ,Gene Frequency ,Genetic Loci ,Genetic Variation ,Genome-Wide Association Study ,Humans ,Linkage Disequilibrium ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Quantitative Trait ,Heritable ,Sex Factors ,Biomedical and clinical sciences ,Health sciences - Abstract
Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P
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- 2021
22. Plasma circulating microRNAs associated with obesity, body fat distribution, and fat mass: the Rotterdam Study
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Abozaid, Yasir J., Zhang, Xiaofang, Mens, Michelle M. J., Ahmadizar, Fariba, Limpens, Marlou, Ikram, M. Arfan, Rivadeneira, Fernando, Voortman, Trudy, Kavousi, Maryam, and Ghanbari, Mohsen
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- 2022
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23. Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
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Hahn, Julie, Fu, Yi-Ping, Brown, Michael R, Bis, Joshua C, de Vries, Paul S, Feitosa, Mary F, Yanek, Lisa R, Weiss, Stefan, Giulianini, Franco, Smith, Albert Vernon, Guo, Xiuqing, Bartz, Traci M, Becker, Diane M, Becker, Lewis C, Boerwinkle, Eric, Brody, Jennifer A, Chen, Yii-Der Ida, Franco, Oscar H, Grove, Megan, Harris, Tamara B, Hofman, Albert, Hwang, Shih-Jen, Kral, Brian G, Launer, Lenore J, Markus, Marcello RP, Rice, Kenneth M, Rich, Stephen S, Ridker, Paul M, Rivadeneira, Fernando, Rotter, Jerome I, Sotoodehnia, Nona, Taylor, Kent D, Uitterlinden, André G, Völker, Uwe, Völzke, Henry, Yao, Jie, Chasman, Daniel I, Dörr, Marcus, Gudnason, Vilmundur, Mathias, Rasika A, Post, Wendy, Psaty, Bruce M, Dehghan, Abbas, O’Donnell, Christopher J, and Morrison, Alanna C
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Heart Disease ,Heart Disease - Coronary Heart Disease ,Human Genome ,Aging ,Clinical Research ,Cardiovascular ,2.4 Surveillance and distribution ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Coronary Artery Disease ,Cross-Sectional Studies ,Europe ,Genetic Loci ,Genome-Wide Association Study ,Humans ,Myocardial Infarction ,Polymorphism ,Single Nucleotide ,Prospective Studies ,White People ,General Science & Technology - Abstract
BackgroundGenome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome.Methods and resultsUsing samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event.ConclusionThis study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.
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- 2020
24. The gut microbiome and child mental health: A population-based study
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Kraaij, Robert, Schuurmans, Isabel K., Radjabzadeh, Djawad, Tiemeier, Henning, Dinan, Timothy G., Uitterlinden, André G., Hillegers, Manon, Jaddoe, Vincent W.V., Duijts, Liesbeth, Moll, Henriette, Rivadeneira, Fernando, Medina-Gomez, Carolina, Jansen, Pauline W., and Cecil, Charlotte A.M.
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- 2023
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25. A saturated map of common genetic variants associated with human height
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Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., and Hirschhorn, Joel N.
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- 2022
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26. Dietary advanced glycation end-products (dAGEs) intake and its relation to sarcopenia and frailty – The Rotterdam Study
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Waqas, Komal, Chen, Jinluan, Lu, T., van der Eerden, B.C.J., Rivadeneira, Fernando, Uitterlinden, André G., Voortman, Trudy, and Zillikens, M. Carola
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- 2022
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27. Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
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Liu, Xueping, Helenius, Dorte, Skotte, Line, Beaumont, Robin N, Wielscher, Matthias, Geller, Frank, Juodakis, Julius, Mahajan, Anubha, Bradfield, Jonathan P, Lin, Frederick TJ, Vogelezang, Suzanne, Bustamante, Mariona, Ahluwalia, Tarunveer S, Pitkänen, Niina, Wang, Carol A, Bacelis, Jonas, Borges, Maria C, Zhang, Ge, Bedell, Bruce A, Rossi, Robert M, Skogstrand, Kristin, Peng, Shouneng, Thompson, Wesley K, Appadurai, Vivek, Lawlor, Debbie A, Kalliala, Ilkka, Power, Christine, McCarthy, Mark I, Boyd, Heather A, Marazita, Mary L, Hakonarson, Hakon, Hayes, M Geoffrey, Scholtens, Denise M, Rivadeneira, Fernando, Jaddoe, Vincent WV, Vinding, Rebecca K, Bisgaard, Hans, Knight, Bridget A, Pahkala, Katja, Raitakari, Olli, Helgeland, Øyvind, Johansson, Stefan, Njølstad, Pål R, Fadista, João, Schork, Andrew J, Nudel, Ron, Miller, Daniel E, Chen, Xiaoting, Weirauch, Matthew T, Mortensen, Preben Bo, Børglum, Anders D, Nordentoft, Merete, Mors, Ole, Hao, Ke, Ryckman, Kelli K, Hougaard, David M, Kottyan, Leah C, Pennell, Craig E, Lyytikainen, Leo-Pekka, Bønnelykke, Klaus, Vrijheid, Martine, Felix, Janine F, Lowe, William L, Grant, Struan FA, Hyppönen, Elina, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Muglia, Louis J, Murray, Jeffrey C, Freathy, Rachel M, Werge, Thomas M, Melbye, Mads, Buil, Alfonso, and Feenstra, Bjarke
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Chromosomes ,Human ,Pair 2 ,Fetus ,Humans ,Premature Birth ,Cytokines ,Gestational Age ,Pregnancy ,Polymorphism ,Single Nucleotide ,Genome ,Human ,Infant ,Newborn ,Female ,Genome-Wide Association Study ,Chromosomes ,Human ,Pair 2 ,Polymorphism ,Single Nucleotide ,Genome ,Infant ,Newborn - Abstract
The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
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- 2019
28. Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels
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Sabater-Lleal, Maria, Huffman, Jennifer E, de Vries, Paul S, Marten, Jonathan, Mastrangelo, Michael A, Song, Ci, Pankratz, Nathan, Ward-Caviness, Cavin K, Yanek, Lisa R, Trompet, Stella, Delgado, Graciela E, Guo, Xiuqing, Bartz, Traci M, Martinez-Perez, Angel, Germain, Marine, de Haan, Hugoline G, Ozel, Ayse B, Polasek, Ozren, Smith, Albert V, Eicher, John D, Reiner, Alex P, Tang, Weihong, Davies, Neil M, Stott, David J, Rotter, Jerome I, Tofler, Geoffrey H, Boerwinkle, Eric, de Maat, Moniek PM, Kleber, Marcus E, Welsh, Paul, Brody, Jennifer A, Chen, Ming-Huei, Vaidya, Dhananjay, Soria, José Manuel, Suchon, Pierre, van Hylckama Vlieg, Astrid, Desch, Karl C, Kolcic, Ivana, Joshi, Peter K, Launer, Lenore J, Harris, Tamara B, Campbell, Harry, Rudan, Igor, Becker, Diane M, Li, Jun Z, Rivadeneira, Fernando, Uitterlinden, André G, Hofman, Albert, Franco, Oscar H, Cushman, Mary, Psaty, Bruce M, Morange, Pierre-Emmanuel, McKnight, Barbara, Chong, Michael R, Fernandez-Cadenas, Israel, Rosand, Jonathan, Lindgren, Arne, Consortium, INVENT Consortium MEGASTROKE Consortium of the International Stroke Genetics, Gudnason, Vilmundur, Wilson, James F, Hayward, Caroline, Ginsburg, David, Fornage, Myriam, Rosendaal, Frits R, Souto, Juan Carlos, Becker, Lewis C, Jenny, Nancy S, März, Winfried, Jukema, J Wouter, Dehghan, Abbas, Trégouët, David-Alexandre, Morrison, Alanna C, Johnson, Andrew D, O’Donnell, Christopher J, Strachan, David P, Lowenstein, Charles J, and Smith, Nicholas L
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Epidemiology ,Health Sciences ,Hematology ,Biotechnology ,Rare Diseases ,Genetics ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Blood ,Cardiovascular ,Arterial Occlusive Diseases ,Biomarkers ,Blood Coagulation ,Blood Coagulation Disorders ,Inherited ,Factor VIII ,Genetic Loci ,Genetic Markers ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Mendelian Randomization Analysis ,Phenotype ,Ribosomal Protein L3 ,Risk Factors ,Venous Thrombosis ,von Willebrand Factor ,cardiovascular diseases ,factor VIII ,genome-wide association studies ,genetics ,risk factors ,von Willebrand factor ,INVENT Consortium ,MEGASTROKE Consortium of the International Stroke Genetics Consortium ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences ,Sports science and exercise - Abstract
BackgroundFactor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are associated with risk of arterial and venous thrombosis and with hemorrhagic disorders. We aimed to identify and functionally test novel genetic associations regulating plasma FVIII and VWF.MethodsWe meta-analyzed genome-wide association results from 46 354 individuals of European, African, East Asian, and Hispanic ancestry. All studies performed linear regression analysis using an additive genetic model and associated ≈35 million imputed variants with natural log-transformed phenotype levels. In vitro gene silencing in cultured endothelial cells was performed for candidate genes to provide additional evidence on association and function. Two-sample Mendelian randomization analyses were applied to test the causal role of FVIII and VWF plasma levels on the risk of arterial and venous thrombotic events.ResultsWe identified 13 novel genome-wide significant ( P≤2.5×10-8) associations, 7 with FVIII levels ( FCHO2/TMEM171/TNPO1, HLA, SOX17/RP1, LINC00583/NFIB, RAB5C-KAT2A, RPL3/TAB1/SYNGR1, and ARSA) and 11 with VWF levels ( PDHB/PXK/KCTD6, SLC39A8, FCHO2/TMEM171/TNPO1, HLA, GIMAP7/GIMAP4, OR13C5/NIPSNAP, DAB2IP, C2CD4B, RAB5C-KAT2A, TAB1/SYNGR1, and ARSA), beyond 10 previously reported associations with these phenotypes. Functional validation provided further evidence of association for all loci on VWF except ARSA and DAB2IP. Mendelian randomization suggested causal effects of plasma FVIII activity levels on venous thrombosis and coronary artery disease risk and plasma VWF levels on ischemic stroke risk.ConclusionsThe meta-analysis identified 13 novel genetic loci regulating FVIII and VWF plasma levels, 10 of which we validated functionally. We provide some evidence for a causal role of these proteins in thrombotic events.
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- 2019
29. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.
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Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S, Finan, Chris, Bis, Joshua C, Huntley, Rachael P, Lovering, Ruth C, Tajuddin, Salman M, Winkler, Thomas W, Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V, Hofer, Edith, van Leeuwen, Elisabeth M, Nolte, Ilja M, Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkänen, Niina, Franzén, Oscar, Joshi, Peter K, Noordam, Raymond, Marioni, Riccardo E, Hwang, Shih-Jen, Musani, Solomon K, Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B, Hofman, Albert, Teumer, Alexander, Cox, Amanda J, Uitterlinden, André G, Wong, Andrew, Smit, Andries J, Newman, Anne B, Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W, Langefeld, Carl D, Wassel, Christina L, Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H, Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E, Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Völzke, Henry, Markus, Hugh S, Deary, Ian J, Jukema, J Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C, Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D, Dhana, Klodian, Kiemeney, Lambertus ALM, Lind, Lars, Raffield, Laura M, Launer, Lenore J, Holdt, Lesca M, Dörr, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A, Melander, Olle, Raitakari, Olli, Franco, Oscar H, Rueda-Ochoa, Oscar L, Roussos, Panos, Whincup, Peter H, Amouyel, Philippe, and Giral, Philippe
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MEGASTROKE Consortium ,Humans ,Coronary Disease ,Genetic Predisposition to Disease ,Amino Acid Oxidoreductases ,Protein-Lysine 6-Oxidase ,Risk Factors ,Lod Score ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Genome-Wide Association Study ,Plaque ,Atherosclerotic ,Carotid Intima-Media Thickness ,ADAMTS9 Protein ,Plaque ,Atherosclerotic ,Polymorphism ,Single Nucleotide - Abstract
Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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- 2018
30. The health effects of vitamin D supplementation: evidence from human studies
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Bouillon, Roger, Manousaki, Despoina, Rosen, Cliff, Trajanoska, Katerina, Rivadeneira, Fernando, and Richards, J. Brent
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- 2022
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31. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
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Winkler, Thomas W., Rasheed, Humaira, Teumer, Alexander, Gorski, Mathias, Rowan, Bryce X., Stanzick, Kira J., Thomas, Laurent F., Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y., Tayo, Bamidele, Thio, Chris H. L., Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B., Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano, Wuttke, Matthias, van der Most, Peter J., Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abbas, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P. J., Zonderman, Alan B., Smith, Albert V., Oldehinkel, Albertine J., De Grandi, Alessandro, Rosenkranz, Alexander R., Franke, Andre, Teren, Andrej, Metspalu, Andres, Hicks, Andrew A., Morris, Andrew P., Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I., Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I., Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K., Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H., Ning, Boting, Penninx, Brenda W. J. H., Vanderwerff, Brett R., Psaty, Bruce M., Kammerer, Candace M., Langefeld, Carl D., Hayward, Caroline, Spracklen, Cassandra N., Robinson-Cohen, Cassianne, Hartman, Catharina A., Lindgren, Cecilia M., Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M., Schulz, Christina-Alexandra, Willer, Cristen J., Chasman, Daniel I., Gudbjartsson, Daniel F., Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J., Waterworth, Dawn M., Mascalzoni, Deborah, Mook-Kanamori, Dennis O., Reilly, Dermot F., Daw, E. Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N., Delgado, Graciela E., Montgomery, Grant W., Snieder, Harold, Campbell, Harry, White, Harvey D., Gao, He, Stringham, Heather M., Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holgen, Kramer, Holly, Rudan, Igor, Nolte, Ilja M., Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P., Wilson, James F., Halbritter, Jan, Felix, Janine F., Divers, Jasmin, Kooner, Jaspal S., Lee, Jeannette Jen-Mai, O’Connell, Jeffrey, Rotter, Jerome I., Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C., Whitfield, John B., Gaziano, John M., Marten, Jonathan, Coresh, Josef, Jonas, Jost B., Mychaleckyj, Josyf C., Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L., Endlich, Karlhans, Dittrich, Katalin, Ryan, Kathleen A., Rice, Kenneth M., Taylor, Kent D., Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lars, Wallentin, Lars, Yerges-Armstrong, Laura M., Raffield, Laura M., Phillips, Lawrence S., Launer, Lenore J., Lyytikäinen, Leo-Pekka, Lange, Leslie A., Citterio, Lorena, Klaric, Lucija, Ikram, M. Arfan, Ising, Marcus, Kleber, Marcus E., Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Markus, Perola, Markus, de Borst, Martin H., Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F., Biggs, Mary L., Wojczynski, Mary K., Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthias, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H., Stumvoll, Michael, Province, Michael A., Evans, Michele K., O’Donoghue, Michelle L., Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A., Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G., Tan, Nicholas Y. Q., Palmer, Nicholette D., Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T., Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P., Sulem, Patrick, Magnusson, Patrik K. E., Elliott, Paul, Ridker, Paul M., Hamet, Pavel, Svensson, Per O., Joshi, Peter K., Kovacs, Peter, Pramstaller, Peter P., Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z. H., Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M., Carroll, Robert J., Gansevoort, Ron T., Loos, Ruth J. F., Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A., Graham, Sarah E., Gordon, Scott D., Hwang, Shih-Jen, Kerr, Shona M., Vaccargiu, Simona, Patil, Snehal B., Hallan, Stein, Bakker, Stephan J. L., Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S., Lehtimäki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tõnu, Haller, Toomas, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmantas, Gudnason, Vilmundur, Jaddoe, Vincent W. V., Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Stark, Klaus J., Stefansson, Kari, Böger, Carsten A., Hung, Adriana M., Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, and Heid, Iris M.
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- 2022
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32. Combining genome-wide association studies highlight novel loci involved in human facial variation
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Xiong, Ziyi, Gao, Xingjian, Chen, Yan, Feng, Zhanying, Pan, Siyu, Lu, Haojie, Uitterlinden, Andre G., Nijsten, Tamar, Ikram, Arfan, Rivadeneira, Fernando, Ghanbari, Mohsen, Wang, Yong, Kayser, Manfred, and Liu, Fan
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- 2022
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33. Bone fragility in diabetes: novel concepts and clinical implications
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Hofbauer, Lorenz C, Busse, Björn, Eastell, Richard, Ferrari, Serge, Frost, Morten, Müller, Ralph, Burden, Andrea M, Rivadeneira, Fernando, Napoli, Nicola, and Rauner, Martina
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- 2022
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34. A comparison of genotyping arrays
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Verlouw, Joost A. M., Clemens, Eva, de Vries, Jard H., Zolk, Oliver, Verkerk, Annemieke J. M. H., am Zehnhoff-Dinnesen, Antoinette, Medina-Gomez, Carolina, Lanvers-Kaminsky, Claudia, Rivadeneira, Fernando, Langer, Thorsten, van Meurs, Joyce B. J., van den Heuvel-Eibrink, Marry M., Uitterlinden, André G., and Broer, Linda
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- 2021
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35. Genome‐Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent
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Smith, Caren E, Follis, Jack L, Dashti, Hassan S, Tanaka, Toshiko, Graff, Mariaelisa, Fretts, Amanda M, Kilpeläinen, Tuomas O, Wojczynski, Mary K, Richardson, Kris, Nalls, Mike A, Schulz, Christina‐Alexandra, Liu, Yongmei, Frazier‐Wood, Alexis C, van Eekelen, Esther, Wang, Carol, de Vries, Paul S, Mikkilä, Vera, Rohde, Rebecca, Psaty, Bruce M, Hansen, Torben, Feitosa, Mary F, Lai, Chao‐Qiang, Houston, Denise K, Ferruci, Luigi, Ericson, Ulrika, Wang, Zhe, de Mutsert, Renée, Oddy, Wendy H, de Jonge, Ester AL, Seppälä, Ilkka, Justice, Anne E, Lemaitre, Rozenn N, Sørensen, Thorkild IA, Province, Michael A, Parnell, Laurence D, Garcia, Melissa E, Bandinelli, Stefania, Orho‐Melander, Marju, Rich, Stephen S, Rosendaal, Frits R, Pennell, Craig E, Jong, Jessica C Kiefte‐de, Kähönen, Mika, Young, Kristin L, Pedersen, Oluf, Aslibekyan, Stella, Rotter, Jerome I, Mook‐Kanamori, Dennis O, Zillikens, M Carola, Raitakari, Olli T, North, Kari E, Overvad, Kim, Arnett, Donna K, Hofman, Albert, Lehtimäki, Terho, Tjønneland, Anne, Uitterlinden, André G, Rivadeneira, Fernando, Franco, Oscar H, German, J Bruce, Siscovick, David S, Cupples, L Adrienne, and Ordovás, José M
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Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Genetics ,Prevention ,Nutrition ,Obesity ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Cancer ,Metabolic and endocrine ,Actins ,Adult ,Aged ,Body Mass Index ,Cohort Studies ,Cross-Sectional Studies ,Dairy Products ,Female ,Gene Frequency ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,Middle Aged ,Myosin-Light-Chain Phosphatase ,Polymorphism ,Single Nucleotide ,White People ,body mass index ,CHARGE consortium ,dairy intake ,genome-wide interaction study ,meta-analysis ,Food Sciences ,Public Health and Health Services ,Food Science ,Nutrition & Dietetics ,Food sciences ,Nutrition and dietetics - Abstract
ScopeBody weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption.Methods and resultsA genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction
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- 2018
36. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
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Jiang, Xia, O’Reilly, Paul F, Aschard, Hugues, Hsu, Yi-Hsiang, Richards, J Brent, Dupuis, Josée, Ingelsson, Erik, Karasik, David, Pilz, Stefan, Berry, Diane, Kestenbaum, Bryan, Zheng, Jusheng, Luan, Jianan, Sofianopoulou, Eleni, Streeten, Elizabeth A, Albanes, Demetrius, Lutsey, Pamela L, Yao, Lu, Tang, Weihong, Econs, Michael J, Wallaschofski, Henri, Völzke, Henry, Zhou, Ang, Power, Chris, McCarthy, Mark I, Michos, Erin D, Boerwinkle, Eric, Weinstein, Stephanie J, Freedman, Neal D, Huang, Wen-Yi, Van Schoor, Natasja M, van der Velde, Nathalie, Groot, Lisette CPGM de, Enneman, Anke, Cupples, L Adrienne, Booth, Sarah L, Vasan, Ramachandran S, Liu, Ching-Ti, Zhou, Yanhua, Ripatti, Samuli, Ohlsson, Claes, Vandenput, Liesbeth, Lorentzon, Mattias, Eriksson, Johan G, Shea, M Kyla, Houston, Denise K, Kritchevsky, Stephen B, Liu, Yongmei, Lohman, Kurt K, Ferrucci, Luigi, Peacock, Munro, Gieger, Christian, Beekman, Marian, Slagboom, Eline, Deelen, Joris, Heemst, Diana van, Kleber, Marcus E, März, Winfried, de Boer, Ian H, Wood, Alexis C, Rotter, Jerome I, Rich, Stephen S, Robinson-Cohen, Cassianne, den Heijer, Martin, Jarvelin, Marjo-Riitta, Cavadino, Alana, Joshi, Peter K, Wilson, James F, Hayward, Caroline, Lind, Lars, Michaëlsson, Karl, Trompet, Stella, Zillikens, M Carola, Uitterlinden, Andre G, Rivadeneira, Fernando, Broer, Linda, Zgaga, Lina, Campbell, Harry, Theodoratou, Evropi, Farrington, Susan M, Timofeeva, Maria, Dunlop, Malcolm G, Valdes, Ana M, Tikkanen, Emmi, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Raitakari, Olli T, Mikkilä, Vera, Ikram, M Arfan, Sattar, Naveed, Jukema, J Wouter, Wareham, Nicholas J, Langenberg, Claudia, Forouhi, Nita G, Gundersen, Thomas E, Khaw, Kay-Tee, Butterworth, Adam S, Danesh, John, and Spector, Timothy
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Amidohydrolases ,Autoimmune Diseases ,Cohort Studies ,Female ,Genome-Wide Association Study ,Humans ,Male ,Polymorphism ,Single Nucleotide ,Vesicular Transport Proteins ,Vitamin D ,White People - Abstract
Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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- 2018
37. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals
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Bihlmeyer, Nathan A, Brody, Jennifer A, Smith, Albert Vernon, Warren, Helen R, Lin, Honghuang, Isaacs, Aaron, Liu, Ching-Ti, Marten, Jonathan, Radmanesh, Farid, Hall, Leanne M, Grarup, Niels, Mei, Hao, Müller-Nurasyid, Martina, Huffman, Jennifer E, Verweij, Niek, Guo, Xiuqing, Yao, Jie, Li-Gao, Ruifang, van den Berg, Marten, Weiss, Stefan, Prins, Bram P, van Setten, Jessica, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Bis, Joshua C, Austin, Tom, Chen, Yii-Der Ida, Psaty, Bruce M, Harrris, Tamara B, Launer, Lenore J, Padmanabhan, Sandosh, Dominiczak, Anna, Huang, Paul L, Xie, Zhijun, Ellinor, Patrick T, Kors, Jan A, Campbell, Archie, Murray, Alison D, Nelson, Christopher P, Tobin, Martin D, Bork-Jensen, Jette, Hansen, Torben, Pedersen, Oluf, Linneberg, Allan, Sinner, Moritz F, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Perz, Siegfried, Kolcic, Ivana, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Lin, Henry J, Taylor, Kent D, de Mutsert, Renée, Trompet, Stella, Jukema, J Wouter, Maan, Arie C, Stricker, Bruno HC, Rivadeneira, Fernando, Uitterlinden, André, Völker, Uwe, Homuth, Georg, Völzke, Henry, Felix, Stephan B, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Raitakari, Olli T, Kähönen, Mika, Mononen, Nina, Gudnason, Vilmundur, Munroe, Patricia B, Lubitz, Steven A, van Duijn, Cornelia M, Newton-Cheh, Christopher H, Hayward, Caroline, Rosand, Jonathan, Samani, Nilesh J, Kanters, Jørgen K, Wilson, James G, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Rotter, Jerome I, Mook-Kanamori, Dennis O, Eijgelsheim, Mark, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Arking, Dan E, and Sotoodehnia, Nona
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Heart Disease ,Prevention ,Genetics ,Cardiovascular ,2.1 Biological and endogenous factors ,Aetiology ,Antiporters ,DNA-Binding Proteins ,Electrocardiography ,Exome ,Genome-Wide Association Study ,Humans ,Long QT Syndrome ,Oligonucleotide Array Sequence Analysis ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Receptors ,Calcium-Sensing ,Transcription Factors ,arrhythmias ,cardiac ,death ,sudden ,cardiac ,genetics ,genome ,humans ,Medical Biotechnology ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundQT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest.Methods and resultsWe performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci.ConclusionsOur analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.
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- 2018
38. Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
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Medina-Gomez, Carolina, Kemp, John P, Trajanoska, Katerina, Luan, Jian’an, Chesi, Alessandra, Ahluwalia, Tarunveer S, Mook-Kanamori, Dennis O, Ham, Annelies, Hartwig, Fernando P, Evans, Daniel S, Joro, Raimo, Nedeljkovic, Ivana, Zheng, Hou-Feng, Zhu, Kun, Atalay, Mustafa, Liu, Ching-Ti, Nethander, Maria, Broer, Linda, Porleifsson, Gudmar, Mullin, Benjamin H, Handelman, Samuel K, Nalls, Mike A, Jessen, Leon E, Heppe, Denise HM, Richards, J Brent, Wang, Carol, Chawes, Bo, Schraut, Katharina E, Amin, Najaf, Wareham, Nick, Karasik, David, Van der Velde, Nathalie, Ikram, M Arfan, Zemel, Babette S, Zhou, Yanhua, Carlsson, Christian J, Liu, Yongmei, McGuigan, Fiona E, Boer, Cindy G, Bønnelykke, Klaus, Ralston, Stuart H, Robbins, John A, Walsh, John P, Zillikens, M Carola, Langenberg, Claudia, Li-Gao, Ruifang, Williams, Frances MK, Harris, Tamara B, Akesson, Kristina, Jackson, Rebecca D, Sigurdsson, Gunnar, Heijer, Martin den, van der Eerden, Bram CJ, van de Peppel, Jeroen, Spector, Timothy D, Pennell, Craig, Horta, Bernardo L, Felix, Janine F, Zhao, Jing Hua, Wilson, Scott G, de Mutsert, Renée, Bisgaard, Hans, Styrkársdóttir, Unnur, Jaddoe, Vincent W, Orwoll, Eric, Lakka, Timo A, Scott, Robert, Grant, Struan FA, Lorentzon, Mattias, van Duijn, Cornelia M, Wilson, James F, Stefansson, Kari, Psaty, Bruce M, Kiel, Douglas P, Ohlsson, Claes, Ntzani, Evangelia, van Wijnen, Andre J, Forgetta, Vincenzo, Ghanbari, Mohsen, Logan, John G, Williams, Graham R, Bassett, JH Duncan, Croucher, Peter I, Evangelou, Evangelos, Uitterlinden, Andre G, Ackert-Bicknell, Cheryl L, Tobias, Jonathan H, Evans, David M, and Rivadeneira, Fernando
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Rare Diseases ,Aging ,Human Genome ,Osteoporosis ,Clinical Research ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Musculoskeletal ,Good Health and Well Being ,Adolescent ,Age Factors ,Animals ,Bone Density ,Child ,Child ,Preschool ,Genetic Loci ,Genome-Wide Association Study ,Humans ,Infant ,Infant ,Newborn ,Mice ,Knockout ,Polymorphism ,Single Nucleotide ,Quantitative Trait ,Heritable ,Regression Analysis ,BMD ,CREB3L1 ,ESR1 ,GWASs ,RANKL ,age-dependent effects ,bone mineral density ,fracture ,genetic correlation ,genome-wide association studies ,meta-regression ,total-body DXA ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.
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- 2018
39. Association between BMD and coronary artery calcification: an observational and Mendelian randomization study
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Lu, Haojie, primary, Lary, Christine W, additional, Hodonsky, Chani J, additional, Peyser, Patricia A, additional, Bos, Daniel, additional, van der Laan, Sander W, additional, Miller, Clint L, additional, Rivadeneira, Fernando, additional, Kiel, Douglas P, additional, Kavousi, Maryam, additional, and Medina-Gomez, Carolina, additional
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- 2024
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40. Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood
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Zheng, Yan, Huang, Tao, Wang, Tiange, Mei, Zhendong, Sun, Zhonghan, Zhang, Tao, Ellervik, Christina, Chai, Jin-Fang, Sim, Xueling, van Dam, Rob M., Tai, E-Shyong, Koh, Woon-Puay, Dorajoo, Rajkumar, Saw, Seang-Mei, Sabanayagam, Charumathi, Wong, Tien Yin, Gupta, Preeti, Rossing, Peter, Ahluwalia, Tarunveer S., Vinding, Rebecca K., Bisgaard, Hans, Bønnelykke, Klaus, Wang, Yujie, Graff, Mariaelisa, Voortman, Trudy, van Rooij, Frank J. A., Hofman, Albert, van Heemst, Diana, Noordam, Raymond, Estampador, Angela C., Varga, Tibor V., Enzenbach, Cornelia, Scholz, Markus, Thiery, Joachim, Burkhardt, Ralph, Orho-Melander, Marju, Schulz, Christina-Alexandra, Ericson, Ulrika, Sonestedt, Emily, Kubo, Michiaki, Akiyama, Masato, Zhou, Ang, Kilpeläinen, Tuomas O., Hansen, Torben, Kleber, Marcus E., Delgado, Graciela, McCarthy, Mark, Lemaitre, Rozenn N., Felix, Janine F., Jaddoe, Vincent W. V., Wu, Ying, Mohlke, Karen L., Lehtimäki, Terho, Wang, Carol A., Pennell, Craig E., Schunkert, Heribert, Kessler, Thorsten, Zeng, Lingyao, Willenborg, Christina, Peters, Annette, Lieb, Wolfgang, Grote, Veit, Rzehak, Peter, Koletzko, Berthold, Erdmann, Jeanette, Munz, Matthias, Wu, Tangchun, He, Meian, Yu, Caizheng, Lecoeur, Cécile, Froguel, Philippe, Corella, Dolores, Moreno, Luis A., Lai, Chao-Qiang, Pitkänen, Niina, Boreham, Colin A., Ridker, Paul M., Rosendaal, Frits R., de Mutsert, Renée, Power, Chris, Paternoster, Lavinia, Sørensen, Thorkild I. A., Tjønneland, Anne, Overvad, Kim, Djousse, Luc, Rivadeneira, Fernando, Lee, Nanette R., Raitakari, Olli T., Kähönen, Mika, Viikari, Jorma, Langhendries, Jean-Paul, Escribano, Joaquin, Verduci, Elvira, Dedoussis, George, König, Inke, Balkau, Beverley, Coltell, Oscar, Dallongeville, Jean, Meirhaeghe, Aline, Amouyel, Philippe, Gottrand, Frédéric, Pahkala, Katja, Niinikoski, Harri, Hyppönen, Elina, März, Winfried, Mackey, David A., Gruszfeld, Dariusz, Tucker, Katherine L., Fumeron, Frédéric, Estruch, Ramon, Ordovas, Jose M., Arnett, Donna K., Mook-Kanamori, Dennis O., Mozaffarian, Dariush, Psaty, Bruce M., North, Kari E., Chasman, Daniel I., and Qi, Lu
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- 2020
41. Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis
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Manousaki, Despoina, Dudding, Tom, Haworth, Simon, Hsu, Yi-Hsiang, Liu, Ching-Ti, Medina-Gómez, Carolina, Voortman, Trudy, van der Velde, Nathalie, Melhus, Håkan, Robinson-Cohen, Cassianne, Cousminer, Diana L, Nethander, Maria, Vandenput, Liesbeth, Noordam, Raymond, Forgetta, Vincenzo, Greenwood, Celia MT, Biggs, Mary L, Psaty, Bruce M, Rotter, Jerome I, Zemel, Babette S, Mitchell, Jonathan A, Taylor, Bruce, Lorentzon, Mattias, Karlsson, Magnus, Jaddoe, Vincent VW, Tiemeier, Henning, Campos-Obando, Natalia, Franco, Oscar H, Utterlinden, Andre G, Broer, Linda, van Schoor, Natasja M, Ham, Annelies C, Ikram, M Arfan, Karasik, David, de Mutsert, Renée, Rosendaal, Frits R, Heijer, Martin den, Wang, Thomas J, Lind, Lars, Orwoll, Eric S, Mook-Kanamori, Dennis O, Michaëlsson, Karl, Kestenbaum, Bryan, Ohlsson, Claes, Mellström, Dan, de Groot, Lisette CPGM, Grant, Struan FA, Kiel, Douglas P, Zillikens, M Carola, Rivadeneira, Fernando, Sawcer, Stephen, Timpson, Nicholas J, and Richards, J Brent
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Biological Sciences ,Health Sciences ,Genetics ,Prevention ,Multiple Sclerosis ,Nutrition ,Autoimmune Disease ,Neurodegenerative ,Human Genome ,Neurosciences ,Brain Disorders ,2.1 Biological and endogenous factors ,Neurological ,Cholestanetriol 26-Monooxygenase ,Cytochrome P450 Family 2 ,Gene Frequency ,Genetic Predisposition to Disease ,Genome ,Human ,Genome-Wide Association Study ,Humans ,Polymorphism ,Single Nucleotide ,Risk Factors ,Vitamin D ,Vitamin D Deficiency ,GWAS ,low-frequency genetic variants ,multiple sclerosis ,vitamin D ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 × 10-88). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 × 10-12). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 × 10-5) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.
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- 2017
42. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness.
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Willems, Sara M, Wright, Daniel J, Day, Felix R, Trajanoska, Katerina, Joshi, Peter K, Morris, John A, Matteini, Amy M, Garton, Fleur C, Grarup, Niels, Oskolkov, Nikolay, Thalamuthu, Anbupalam, Mangino, Massimo, Liu, Jun, Demirkan, Ayse, Lek, Monkol, Xu, Liwen, Wang, Guan, Oldmeadow, Christopher, Gaulton, Kyle J, Lotta, Luca A, Miyamoto-Mikami, Eri, Rivas, Manuel A, White, Tom, Loh, Po-Ru, Aadahl, Mette, Amin, Najaf, Attia, John R, Austin, Krista, Benyamin, Beben, Brage, Søren, Cheng, Yu-Ching, Cięszczyk, Paweł, Derave, Wim, Eriksson, Karl-Fredrik, Eynon, Nir, Linneberg, Allan, Lucia, Alejandro, Massidda, Myosotis, Mitchell, Braxton D, Miyachi, Motohiko, Murakami, Haruka, Padmanabhan, Sandosh, Pandey, Ashutosh, Papadimitriou, Ioannis, Rajpal, Deepak K, Sale, Craig, Schnurr, Theresia M, Sessa, Francesco, Shrine, Nick, Tobin, Martin D, Varley, Ian, Wain, Louise V, Wray, Naomi R, Lindgren, Cecilia M, MacArthur, Daniel G, Waterworth, Dawn M, McCarthy, Mark I, Pedersen, Oluf, Khaw, Kay-Tee, Kiel, Douglas P, GEFOS Any-Type of Fracture Consortium, Pitsiladis, Yannis, Fuku, Noriyuki, Franks, Paul W, North, Kathryn N, van Duijn, Cornelia M, Mather, Karen A, Hansen, Torben, Hansson, Ola, Spector, Tim, Murabito, Joanne M, Richards, J Brent, Rivadeneira, Fernando, Langenberg, Claudia, Perry, John RB, Wareham, Nick J, and Scott, Robert A
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GEFOS Any-Type of Fracture Consortium ,Hand ,Humans ,Actins ,Transforming Growth Factor alpha ,Membrane Proteins ,Neoplasm Proteins ,Nuclear Proteins ,Repressor Proteins ,Hand Strength ,Cohort Studies ,Genetics ,Population ,Polymorphism ,Single Nucleotide ,Adult ,Aged ,Middle Aged ,European Continental Ancestry Group ,Female ,Male ,Genome-Wide Association Study ,Genetic Loci ,United Kingdom ,Prevention ,Genetics ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Musculoskeletal - Abstract
Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P
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- 2017
43. Discovery of novel heart rate-associated loci using the Exome Chip
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van den Berg, Marten E, Warren, Helen R, Cabrera, Claudia P, Verweij, Niek, Mifsud, Borbala, Haessler, Jeffrey, Bihlmeyer, Nathan A, Fu, Yi-Ping, Weiss, Stefan, Lin, Henry J, Grarup, Niels, Li-Gao, Ruifang, Pistis, Giorgio, Shah, Nabi, Brody, Jennifer A, Müller-Nurasyid, Martina, Lin, Honghuang, Mei, Hao, Smith, Albert V, Lyytikäinen, Leo-Pekka, Hall, Leanne M, van Setten, Jessica, Trompet, Stella, Prins, Bram P, Isaacs, Aaron, Radmanesh, Farid, Marten, Jonathan, Entwistle, Aiman, Kors, Jan A, Silva, Claudia T, Alonso, Alvaro, Bis, Joshua C, de Boer, Rudolf, de Haan, Hugoline G, de Mutsert, Renée, Dedoussis, George, Dominiczak, Anna F, Doney, Alex SF, Ellinor, Patrick T, Eppinga, Ruben N, Felix, Stephan B, Guo, Xiuqing, Hagemeijer, Yanick, Hansen, Torben, Harris, Tamara B, Heckbert, Susan R, Huang, Paul L, Hwang, Shih-Jen, Kähönen, Mika, Kanters, Jørgen K, Kolcic, Ivana, Launer, Lenore J, Li, Man, Yao, Jie, Linneberg, Allan, Liu, Simin, Macfarlane, Peter W, Mangino, Massimo, Morris, Andrew D, Mulas, Antonella, Murray, Alison D, Nelson, Christopher P, Orrú, Marco, Padmanabhan, Sandosh, Peters, Annette, Porteous, David J, Poulter, Neil, Psaty, Bruce M, Qi, Lihong, Raitakari, Olli T, Rivadeneira, Fernando, Roselli, Carolina, Rudan, Igor, Sattar, Naveed, Sever, Peter, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Timothy D, Stanton, Alice V, Stirrups, Kathleen E, Taylor, Kent D, Tobin, Martin D, Uitterlinden, André, Vaartjes, Ilonca, Hoes, Arno W, van der Meer, Peter, Völker, Uwe, Waldenberger, Melanie, Xie, Zhijun, Zoledziewska, Magdalena, Tinker, Andrew, Polasek, Ozren, Rosand, Jonathan, Jamshidi, Yalda, van Duijn, Cornelia M, Zeggini, Eleftheria, Jukema, J Wouter, Asselbergs, Folkert W, Samani, Nilesh J, and Lehtimäki, Terho
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Biological Sciences ,Genetics ,Human Genome ,Biotechnology ,Heart Disease ,Prevention ,Cardiovascular ,Stem Cell Research ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Alleles ,Exome ,Female ,Gene Frequency ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Heart Rate ,Humans ,Male ,Middle Aged ,Oligonucleotide Array Sequence Analysis ,Polymorphism ,Single Nucleotide ,Risk Factors ,White People ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.
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- 2017
44. Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function
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Wild, Philipp S, Felix, Janine F, Schillert, Arne, Teumer, Alexander, Chen, Ming-Huei, Leening, Maarten JG, Völker, Uwe, Großmann, Vera, Brody, Jennifer A, Irvin, Marguerite R, Shah, Sanjiv J, Pramana, Setia, Lieb, Wolfgang, Schmidt, Reinhold, Stanton, Alice V, Malzahn, Dörthe, Smith, Albert Vernon, Sundström, Johan, Minelli, Cosetta, Ruggiero, Daniela, Lyytikäinen, Leo-Pekka, Tiller, Daniel, Smith, J Gustav, Monnereau, Claire, Di Tullio, Marco R, Musani, Solomon K, Morrison, Alanna C, Pers, Tune H, Morley, Michael, Kleber, Marcus E, Aragam, Jayashri, Benjamin, Emelia J, Bis, Joshua C, Bisping, Egbert, Broeckel, Ulrich, Cheng, Susan, Deckers, Jaap W, Del Greco M, Fabiola, Edelmann, Frank, Fornage, Myriam, Franke, Lude, Friedrich, Nele, Harris, Tamara B, Hofer, Edith, Hofman, Albert, Huang, Jie, Hughes, Alun D, Kähönen, Mika, investigators, KNHI, Kruppa, Jochen, Lackner, Karl J, Lannfelt, Lars, Laskowski, Rafael, Launer, Lenore J, Leosdottir, Margrét, Lin, Honghuang, Lindgren, Cecilia M, Loley, Christina, MacRae, Calum A, Mascalzoni, Deborah, Mayet, Jamil, Medenwald, Daniel, Morris, Andrew P, Müller, Christian, Müller-Nurasyid, Martina, Nappo, Stefania, Nilsson, Peter M, Nuding, Sebastian, Nutile, Teresa, Peters, Annette, Pfeufer, Arne, Pietzner, Diana, Pramstaller, Peter P, Raitakari, Olli T, Rice, Kenneth M, Rivadeneira, Fernando, Rotter, Jerome I, Ruohonen, Saku T, Sacco, Ralph L, Samdarshi, Tandaw E, Schmidt, Helena, Sharp, Andrew SP, Shields, Denis C, Sorice, Rossella, Sotoodehnia, Nona, Stricker, Bruno H, Surendran, Praveen, Thom, Simon, Töglhofer, Anna M, Uitterlinden, André G, Wachter, Rolf, Völzke, Henry, Ziegler, Andreas, Münzel, Thomas, März, Winfried, Cappola, Thomas P, Hirschhorn, Joel N, Mitchell, Gary F, Smith, Nicholas L, and Fox, Ervin R
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Human Genome ,Clinical Research ,Prevention ,Heart Disease ,Cardiovascular ,2.1 Biological and endogenous factors ,Aetiology ,Female ,Genetic Loci ,Genome-Wide Association Study ,Heart Diseases ,Humans ,Male ,Myocardium ,Polymorphism ,Single Nucleotide ,Quantitative Trait ,Heritable ,Medical and Health Sciences ,Immunology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundUnderstanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function.MethodsA GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function.ResultsThe discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue.ConclusionThe additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.FundingFor detailed information per study, see Acknowledgments.
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- 2017
45. Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study
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de Vries, Paul S, Sabater-Lleal, Maria, Chasman, Daniel I, Trompet, Stella, Ahluwalia, Tarunveer S, Teumer, Alexander, Kleber, Marcus E, Chen, Ming-Huei, Wang, Jie Jin, Attia, John R, Marioni, Riccardo E, Steri, Maristella, Weng, Lu-Chen, Pool, Rene, Grossmann, Vera, Brody, Jennifer A, Venturini, Cristina, Tanaka, Toshiko, Rose, Lynda M, Oldmeadow, Christopher, Mazur, Johanna, Basu, Saonli, Frånberg, Mattias, Yang, Qiong, Ligthart, Symen, Hottenga, Jouke J, Rumley, Ann, Mulas, Antonella, de Craen, Anton JM, Grotevendt, Anne, Taylor, Kent D, Delgado, Graciela E, Kifley, Annette, Lopez, Lorna M, Berentzen, Tina L, Mangino, Massimo, Bandinelli, Stefania, Morrison, Alanna C, Hamsten, Anders, Tofler, Geoffrey, de Maat, Moniek PM, Draisma, Harmen HM, Lowe, Gordon D, Zoledziewska, Magdalena, Sattar, Naveed, Lackner, Karl J, Völker, Uwe, McKnight, Barbara, Huang, Jie, Holliday, Elizabeth G, McEvoy, Mark A, Starr, John M, Hysi, Pirro G, Hernandez, Dena G, Guan, Weihua, Rivadeneira, Fernando, McArdle, Wendy L, Slagboom, P Eline, Zeller, Tanja, Psaty, Bruce M, Uitterlinden, André G, de Geus, Eco JC, Stott, David J, Binder, Harald, Hofman, Albert, Franco, Oscar H, Rotter, Jerome I, Ferrucci, Luigi, Spector, Tim D, Deary, Ian J, März, Winfried, Greinacher, Andreas, Wild, Philipp S, Cucca, Francesco, Boomsma, Dorret I, Watkins, Hugh, Tang, Weihong, Ridker, Paul M, Jukema, Jan W, Scott, Rodney J, Mitchell, Paul, Hansen, Torben, O'Donnell, Christopher J, Smith, Nicholas L, Strachan, David P, and Dehghan, Abbas
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Genome-Wide Association Study ,HapMap Project ,Humans ,General Science & Technology - Abstract
An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10-8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10-8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.
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- 2017
46. Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2
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Nielson, Carrie M, Liu, Ching‐Ti, Smith, Albert V, Ackert‐Bicknell, Cheryl L, Reppe, Sjur, Jakobsdottir, Johanna, Wassel, Christina, Register, Thomas C, Oei, Ling, Alonso, Nerea, Oei, Edwin H, Parimi, Neeta, Samelson, Elizabeth J, Nalls, Mike A, Zmuda, Joseph, Lang, Thomas, Bouxsein, Mary, Latourelle, Jeanne, Claussnitzer, Melina, Siggeirsdottir, Kristin, Srikanth, Priya, Lorentzen, Erik, Vandenput, Liesbeth, Langefeld, Carl, Raffield, Laura, Terry, Greg, Cox, Amanda J, Allison, Matthew A, Criqui, Michael H, Bowden, Don, Ikram, M Arfan, Mellström, Dan, Karlsson, Magnus K, Carr, John, Budoff, Matthew, Phillips, Caroline, Cupples, L Adrienne, Chou, Wen‐Chi, Myers, Richard H, Ralston, Stuart H, Gautvik, Kaare M, Cawthon, Peggy M, Cummings, Steven, Karasik, David, Rivadeneira, Fernando, Gudnason, Vilmundur, Orwoll, Eric S, Harris, Tamara B, Ohlsson, Claes, Kiel, Douglas P, and Hsu, Yi‐Hsiang
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Biological Sciences ,Biomedical and Clinical Sciences ,Clinical Sciences ,Genetics ,Human Genome ,Aging ,Osteoporosis ,Biomedical Imaging ,Aetiology ,2.1 Biological and endogenous factors ,Musculoskeletal ,Animals ,Biopsy ,Bone Density ,Cancellous Bone ,Excitatory Amino Acid Transporter 1 ,Gene Expression Regulation ,Genetic Association Studies ,Genetic Predisposition to Disease ,Humans ,Linkage Disequilibrium ,Lumbar Vertebrae ,Mice ,Molecular Sequence Annotation ,Organ Size ,Osteoblasts ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Receptor ,EphB2 ,Risk Factors ,Spinal Fractures ,Spine ,BONE QCT ,CT ,ANALYSIS ,QUANTITATION OF BONE ,OSTEOPOROSIS ,DISEASES AND DISORDERS OF ,RELATED TO BONE ,GENERAL POPULATION STUDIES ,EPIDEMIOLOGY ,HUMAN ASSOCIATION STUDIES ,GENETIC RESEARCH ,FRACTURE RISK ASSESSMENT ,ANALYSIS/QUANTITATION OF BONE ,BONE QCT/μCT ,DISEASES AND DISORDERS OF/RELATED TO BONE ,EPIDEMIOLOGY ,HUMAN ASSOCIATION STUDIES ,Engineering ,Medical and Health Sciences ,Anatomy & Morphology ,Biological sciences ,Biomedical and clinical sciences - Abstract
Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n = 21,701) and clinical vertebral fracture (n = 5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF] = 3%) was associated with higher vBMD (β = 0.22, p = 1.9 × 10-8 ) and decreased risk of radiographic vertebral fracture (odds ratio [OR] = 0.75; false discovery rate [FDR] p = 0.01). In 1p36.12, rs12742784 (MAF = 21%) was associated with higher vBMD (β = 0.09, p = 1.2 × 10-10 ) and decreased risk of clinical vertebral fracture (OR = 0.82; FDR p = 7.4 × 10-4 ). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β = 0.28, FDR p = 0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β = 0.12, FDR p = 1.7 × 10-3 , functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence. © 2016 American Society for Bone and Mineral Research.
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- 2016
47. Targeted sequencing of genome wide significant loci associated with bone mineral density (BMD) reveals significant novel and rare variants: the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) targeted sequencing study.
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Hsu, Yi-Hsiang, Li, Guo, Liu, Ching-Ti, Brody, Jennifer A, Karasik, David, Chou, Wen-Chi, Demissie, Serkalem, Nandakumar, Kannabiran, Zhou, Yanhua, Cheng, Chia-Ho, Gill, Richard, Gibbs, Richard A, Muzny, Donna, Santibanez, Jireh, Estrada, Karol, Rivadeneira, Fernando, Harris, Tamara, Gudnason, Vilmundur, Uitterlinden, Andre, Psaty, Bruce M, Robbins, John A, Adrienne Cupples, L, and Kiel, Douglas P
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Biological Sciences ,Genetics ,Human Genome ,Osteoporosis ,2.1 Biological and endogenous factors ,Aetiology ,Aging ,Bone Density ,Cardiovascular Diseases ,Cohort Studies ,Epidemiologic Studies ,Female ,Femur Neck ,GTPase-Activating Proteins ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,MEF2 Transcription Factors ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Medical and Health Sciences ,Genetics & Heredity - Abstract
BackgroundBone mineral density (BMD) is a heritable phenotype that predicts fracture risk. We performed fine-mapping by targeted sequencing at WLS, MEF2C, ARHGAP1/F2 and JAG1 loci prioritized by eQTL and bioinformatic approaches among 56 BMD loci from our previous GWAS meta-analysis. Targeted sequencing was conducted in 1,291 Caucasians from the Framingham Heart Study ( n = 925) and Cardiovascular Health Study ( n = 366), including 206 women and men with extreme low femoral neck (FN) BMD. A total of 4,964 sequence variants (SNVs) were observed and 80% were rare with MAF
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- 2016
48. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis
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Natarajan, Pradeep, Bis, Joshua C, Bielak, Lawrence F, Cox, Amanda J, Dörr, Marcus, Feitosa, Mary F, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, Isaacs, Aaron, Jhun, Min A, Kavousi, Maryam, Li-Gao, Ruifang, Lyytikäinen, Leo-Pekka, Marioni, Riccardo E, Schminke, Ulf, Stitziel, Nathan O, Tada, Hayato, van Setten, Jessica, Smith, Albert V, Vojinovic, Dina, Yanek, Lisa R, Yao, Jie, Yerges-Armstrong, Laura M, Amin, Najaf, Baber, Usman, Borecki, Ingrid B, Carr, J Jeffrey, Chen, Yii-Der Ida, Cupples, L Adrienne, de Jong, Pim A, de Koning, Harry, de Vos, Bob D, Demirkan, Ayse, Fuster, Valentin, Franco, Oscar H, Goodarzi, Mark O, Harris, Tamara B, Heckbert, Susan R, Heiss, Gerardo, Hoffmann, Udo, Hofman, Albert, Išgum, Ivana, Jukema, J Wouter, Kähönen, Mika, Kardia, Sharon LR, Kral, Brian G, Launer, Lenore J, Massaro, Joe, Mehran, Roxana, Mitchell, Braxton D, Mosley, Thomas H, de Mutsert, Renée, Newman, Anne B, Nguyen, Khanh-Dung, North, Kari E, O'Connell, Jeffrey R, Oudkerk, Matthijs, Pankow, James S, Peloso, Gina M, Post, Wendy, Province, Michael A, Raffield, Laura M, Raitakari, Olli T, Reilly, Dermot F, Rivadeneira, Fernando, Rosendaal, Frits, Sartori, Samantha, Taylor, Kent D, Teumer, Alexander, Trompet, Stella, Turner, Stephen T, Uitterlinden, Andre G, Vaidya, Dhananjay, van der Lugt, Aad, Völker, Uwe, Wardlaw, Joanna M, Wassel, Christina L, Weiss, Stefan, Wojczynski, Mary K, Becker, Diane M, Becker, Lewis C, Boerwinkle, Eric, Bowden, Donald W, Deary, Ian J, Dehghan, Abbas, Felix, Stephan B, Gudnason, Vilmundur, Lehtimäki, Terho, Mathias, Rasika, Mook-Kanamori, Dennis O, Psaty, Bruce M, Rader, Daniel J, Rotter, Jerome I, Wilson, James G, van Duijn, Cornelia M, Völzke, Henry, Kathiresan, Sekar, Peyser, Patricia A, and O'Donnell, Christopher J
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Heart Disease - Coronary Heart Disease ,Aging ,Human Genome ,Atherosclerosis ,Cardiovascular ,Heart Disease ,Clinical Research ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Apolipoprotein B-100 ,Apolipoprotein E2 ,Asymptomatic Diseases ,Black People ,Carotid Artery Diseases ,Carotid Intima-Media Thickness ,Cholesterol ,LDL ,Computed Tomography Angiography ,Coronary Angiography ,Coronary Artery Disease ,Exome ,Gene Frequency ,Genetic Markers ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Odds Ratio ,Oligonucleotide Array Sequence Analysis ,Phenotype ,Prognosis ,Risk Assessment ,Risk Factors ,Vascular Calcification ,White People ,carotid intima-media thickness ,coronary artery calcification ,exome ,genome-wide association study ,genomics ,CHARGE Consortium ,carotid intima–media thickness ,Medical Biotechnology ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundThe burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent coronary heart disease.Methods and resultsWe studied a total of 25 109 European ancestry and African ancestry participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52 869 participants with common carotid intima-media thickness measured by ultrasonography within the CHARGE Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology). Participants were genotyped for 247 870 DNA sequence variants (231 539 in exons) across the genome. A meta-analysis of exome-wide association studies was performed across cohorts for CAC and carotid intima-media thickness. APOB p.Arg3527Gln was associated with 4-fold excess CAC (P=3×10-10). The APOE ε2 allele (p.Arg176Cys) was associated with both 22.3% reduced CAC (P=1×10-12) and 1.4% reduced carotid intima-media thickness (P=4×10-14) in carriers compared with noncarriers. In secondary analyses conditioning on low-density lipoprotein cholesterol concentration, the ε2 protective association with CAC, although attenuated, remained strongly significant. Additionally, the presence of ε2 was associated with reduced risk for coronary heart disease (odds ratio 0.77; P=1×10-11).ConclusionsExome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical atherosclerosis. APOE ε2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities, as well as clinical coronary heart disease.
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- 2016
49. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
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Postmus, Iris, Warren, Helen R, Trompet, Stella, Arsenault, Benoit J, Avery, Christy L, Bis, Joshua C, Chasman, Daniel I, de Keyser, Catherine E, Deshmukh, Harshal A, Evans, Daniel S, Feng, QiPing, Li, Xiaohui, Smit, Roelof AJ, Smith, Albert V, Sun, Fangui, Taylor, Kent D, Arnold, Alice M, Barnes, Michael R, Barratt, Bryan J, Betteridge, John, Boekholdt, S Matthijs, Boerwinkle, Eric, Buckley, Brendan M, Chen, Y-D Ida, de Craen, Anton JM, Cummings, Steven R, Denny, Joshua C, Dubé, Marie Pierre, Durrington, Paul N, Eiriksdottir, Gudny, Ford, Ian, Guo, Xiuqing, Harris, Tamara B, Heckbert, Susan R, Hofman, Albert, Hovingh, G Kees, Kastelein, John JP, Launer, Leonore J, Liu, Ching-Ti, Liu, Yongmei, Lumley, Thomas, McKeigue, Paul M, Munroe, Patricia B, Neil, Andrew, Nickerson, Deborah A, Nyberg, Fredrik, O'Brien, Eoin, O'Donnell, Christopher J, Post, Wendy, Poulter, Neil, Vasan, Ramachandran S, Rice, Kenneth, Rich, Stephen S, Rivadeneira, Fernando, Sattar, Naveed, Sever, Peter, Shaw-Hawkins, Sue, Shields, Denis C, Slagboom, P Eline, Smith, Nicholas L, Smith, Joshua D, Sotoodehnia, Nona, Stanton, Alice, Stott, David J, Stricker, Bruno H, Stürmer, Til, Uitterlinden, André G, Wei, Wei-Qi, Westendorp, Rudi GJ, Whitsel, Eric A, Wiggins, Kerri L, Wilke, Russell A, Ballantyne, Christie M, Colhoun, Helen M, Cupples, L Adrienne, Franco, Oscar H, Gudnason, Vilmundur, Hitman, Graham, Palmer, Colin NA, Psaty, Bruce M, Ridker, Paul M, Stafford, Jeanette M, Stein, Charles M, Tardif, Jean-Claude, Caulfield, Mark J, Jukema, J Wouter, Rotter, Jerome I, and Krauss, Ronald M
- Subjects
Atherosclerosis ,Genetics ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Stroke ,Good Health and Well Being ,Cholesterol Ester Transfer Proteins ,Cholesterol ,HDL ,Female ,Genome-Wide Association Study ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Male ,Pharmacogenomic Variants ,Polymorphism ,Single Nucleotide ,Treatment Outcome ,White People ,Genome-wide association study ,HDL-cholesterol ,Statins ,pharmacogenetics ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
BackgroundIn addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.Methods and resultsWe performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p
- Published
- 2016
50. Bone mineral density and the risk of incident dementia:A meta-analysis
- Author
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Lary, Christine W., Ghatan, Samuel, Gerety, Meghan, Hinton, Alexandra, Nagarajan, Archana, Rosen, Clifford, Ross, Ryan D., Bennett, David A., DeStefano, Anita L., Ikram, Mohammad A., Rivadeneira, Fernando, Kiel, Douglas P., Seshadri, Sudha, Beiser, Alexa, Lary, Christine W., Ghatan, Samuel, Gerety, Meghan, Hinton, Alexandra, Nagarajan, Archana, Rosen, Clifford, Ross, Ryan D., Bennett, David A., DeStefano, Anita L., Ikram, Mohammad A., Rivadeneira, Fernando, Kiel, Douglas P., Seshadri, Sudha, and Beiser, Alexa
- Abstract
Background: It is not known whether bone mineral density (BMD) measured at baseline or as the rate of decline prior to baseline (prior bone loss) is a stronger predictor of incident dementia or Alzheimer's disease (AD). Methods:We performed a meta-analysis of three longitudinal studies, the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Rush Memory and Aging Project (MAP), modeling the time to diagnosis of dementia as a function of BMD measures accounting for covariates. We included individuals with one or two BMD assessments, aged ≥60 years, and free of dementia at baseline with follow-up available. BMD was measured at the hip femoral neck using dual-energy X-ray absorptiometry (DXA), or at the heel calcaneus using quantitative ultrasound to calculate estimated BMD (eBMD). BMD at study baseline (“baseline BMD”) and annualized percentage change in BMD prior to baseline (“prior bone loss”) were included as continuous measures. The primary outcome was incident dementia diagnosis within 10 years of baseline, and incident AD was a secondary outcome. Baseline covariates included age, sex, body mass index, ApoE4 genotype, and education. Results: The combined sample size across all three studies was 4431 with 606 incident dementia diagnoses, 498 of which were AD. A meta-analysis of baseline BMD across three studies showed higher BMD to have a significant protective association with incident dementia with a hazard ratio of 0.47 (95% CI: 0.23–0.96; p = 0.038) per increase in g/cm2, or 0.91 (95% CI: 0.84–0.995) per standard deviation increase. We observed a significant association between prior bone loss and incident dementia with a hazard ratio of 1.30 (95% CI: 1.12–1.51; p < 0.001) per percent increase in prior bone loss only in the FHS cohort. Conclusions: Baseline BMD but not prior bone loss was associated with incident dementia in a meta-analysis across three st
- Published
- 2024
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