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1. G protein–coupled receptor kinase 5 regulates thrombin signaling in platelets via PAR-1

Author: Downes, Kate, Zhao, Xuefei, Gleadall, Nicholas S., McKinney, Harriet, Kempster, Carly, Batista, Joana, Thomas, Patrick L., Cooper, Matthew, Michael, James V., Kreuzhuber, Roman, Wedderburn, Katherine, Waller, Kathryn, Varney, Bianca, Verdier, Hippolyte, Kriek, Neline, Ashford, Sofie E., Stirrups, Kathleen E., Dunster, Joanne L., McKenzie, Steven E., Ouwehand, Willem H., Gibbins, Jonathan M., Yang, Jing, Astle, William J., and Ma, Peisong
Published: 2022
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2. Biallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration

Author: Arno, Gavin, Carss, Keren J, Hull, Sarah, Zihni, Ceniz, Robson, Anthony G, Fiorentino, Alessia, Hardcastle, Alison J, Holder, Graham E, Cheetham, Michael E, Plagnol, Vincent, Moore, Anthony, Raymond, F Lucy, Matter, Karl, Balda, Maria S, Webster, Andrew R, Black, Graeme, Hall, Georgina, Ingram, Stuart, Gillespie, Rachel, Manson, Forbes, Sergouniotis, Panagiotis, Inglehearn, Chris, Toomes, Carmel, Ali, Manir, McKibbin, Martin, Poulter, James, Khan, Kamron, Lord, Emma, Nemeth, Andrea, Downes, Susan, Halford, Stephanie, Yu, Jing, Lise, Stefano, Ponitkos, Nikos, Michaelides, Michel, Webster, Andrew, van Heyningen, Veronica, Aitman, Timothy, Alachkar, Hana, Ali, Sonia, Allen, Louise, Allsup, David, Ambegaonkar, Gautum, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arumugakani, Gururaj, Ashford, Sofie, Astle, William, Attwood, Antony, Austin, Steve, Bacchelli, Chiara, Bakchoul, Tamam, Bariana, Tadbir K, Baxendale, Helen, Bennett, David, Bethune, Claire, Bibi, Shahnaz, Bitner-Glindzicz, Maria, Bleda, Marta, Boggard, Harm, Bolton-Maggs, Paula, Booth, Claire, Bradley, John R, Brady, Angie, Brown, Matthew, Browning, Michael, Bryson, Christine, Burns, Siobhan, Calleja, Paul, Canham, Natalie, Carmichael, Jenny, Carss, Keren, Caulfield, Mark, Chalmers, Elizabeth, Chandra, Anita, Chinnery, Patrick, Chitre, Manali, Church, Colin, Clement, Emma, Clements-Brod, Naomi, Clowes, Virginia, Coghlan, Gerry, Collins, Peter, Cooper, Nichola, Creaser-Myers, Amanda, DaCosta, Rosa, Daugherty, Louise, Davies, Sophie, Davis, John, De Vries, Minka, Deegan, Patrick, Deevi, Sri VV, and Deshpande, Charu
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Ophthalmology and Optometry, Human Genome, Rare Diseases, Neurosciences, Eye Disease and Disorders of Vision, Aetiology, 2.1 Biological and endogenous factors, Eye, Adult, Alleles, Amino Acid Sequence, Cell Polarity, Epithelial Cells, Exome, Eye Proteins, Female, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Membrane Proteins, Middle Aged, Mutation, Missense, Nerve Tissue Proteins, Pedigree, Phenotype, Retina, Retinal Degeneration, Retinal Dystrophies, Rho Guanine Nucleotide Exchange Factors, rhoA GTP-Binding Protein, UK Inherited Retinal Disease Consortium, NIHR Bioresource - Rare Diseases Consortium, ARHGEF18, apicobasal polarity, inherited retinal dystrophy, p114RhoGEF, retinal degeneration, retinitis pigmentosa, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract: Mutations in more than 250 genes are implicated in inherited retinal dystrophy; the encoded proteins are involved in a broad spectrum of pathways. The presence of unsolved families after highly parallel sequencing strategies suggests that further genes remain to be identified. Whole-exome and -genome sequencing studies employed here in large cohorts of affected individuals revealed biallelic mutations in ARHGEF18 in three such individuals. ARHGEF18 encodes ARHGEF18, a guanine nucleotide exchange factor that activates RHOA, a small GTPase protein that is a key component of tight junctions and adherens junctions. This biological pathway is known to be important for retinal development and function, as mutation of CRB1, encoding another component, causes retinal dystrophy. The retinal structure in individuals with ARHGEF18 mutations resembled that seen in subjects with CRB1 mutations. Five mutations were found on six alleles in the three individuals: c.808A>G (p.Thr270Ala), c.1617+5G>A (p.Asp540Glyfs∗63), c.1996C>T (p.Arg666∗), c.2632G>T (p.Glu878∗), and c.2738_2761del (p.Arg913_Glu920del). Functional tests suggest that each disease genotype might retain some ARHGEF18 activity, such that the phenotype described here is not the consequence of nullizygosity. In particular, the p.Thr270Ala missense variant affects a highly conserved residue in the DBL homology domain, which is required for the interaction and activation of RHOA. Previously, knock-out of Arhgef18 in the medaka fish has been shown to cause larval lethality which is preceded by retinal defects that resemble those seen in zebrafish Crumbs complex knock-outs. The findings described here emphasize the peculiar sensitivity of the retina to perturbations of this pathway, which is highlighted as a target for potential therapeutic strategies.
Published: 2017

3. Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Author: Carss, Keren J, Arno, Gavin, Erwood, Marie, Stephens, Jonathan, Sanchis-Juan, Alba, Hull, Sarah, Megy, Karyn, Grozeva, Detelina, Dewhurst, Eleanor, Malka, Samantha, Plagnol, Vincent, Penkett, Christopher, Stirrups, Kathleen, Rizzo, Roberta, Wright, Genevieve, Josifova, Dragana, Bitner-Glindzicz, Maria, Scott, Richard H, Clement, Emma, Allen, Louise, Armstrong, Ruth, Brady, Angela F, Carmichael, Jenny, Chitre, Manali, Henderson, Robert HH, Hurst, Jane, MacLaren, Robert E, Murphy, Elaine, Paterson, Joan, Rosser, Elisabeth, Thompson, Dorothy A, Wakeling, Emma, Ouwehand, Willem H, Michaelides, Michel, Moore, Anthony T, Consortium, NIHR-BioResource Rare Diseases, Aitman, Timothy, Alachkar, Hana, Ali, Sonia, Allsup, David, Ambegaonkar, Gautum, Anderson, Julie, Antrobus, Richard, Arumugakani, Gururaj, Ashford, Sofie, Astle, William, Attwood, Antony, Austin, Steve, Bacchelli, Chiara, Bakchoul, Tamam, Bariana, Tadbir K, Baxendale, Helen, Bennett, David, Bethune, Claire, Bibi, Shahnaz, Bleda, Marta, Boggard, Harm, Bolton-Maggs, Paula, Booth, Claire, Bradley, John R, Brady, Angie, Brown, Matthew, Browning, Michael, Bryson, Christine, Burns, Siobhan, Calleja, Paul, Canham, Natalie, Carss, Keren, Caulfield, Mark, Chalmers, Elizabeth, Chandra, Anita, Chinnery, Patrick, Church, Colin, Clements-Brod, Naomi, Clowes, Virginia, Coghlan, Gerry, Collins, Peter, Cooper, Nichola, Creaser-Myers, Amanda, DaCosta, Rosa, Daugherty, Louise, Davies, Sophie, Davis, John, De Vries, Minka, Deegan, Patrick, Deevi, Sri VV, Deshpande, Charu, Devlin, Lisa, Doffinger, Rainer, Dormand, Natalie, Drewe, Elizabeth, and Edgar, David
Subjects: Genetics, Neurosciences, Eye Disease and Disorders of Vision, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Eye, Good Health and Well Being, Adaptor Proteins, Signal Transducing, Alleles, Base Sequence, Choroideremia, DNA Mutational Analysis, Ethnicity, Exome, Female, Genes, Recessive, Genetic Variation, Genome, Human, Humans, Introns, Male, Mutation, Rare Diseases, Retinal Diseases, NIHR-BioResource Rare Diseases Consortium, copy-number variants, rare sequence variant, retinal dystrophy, whole-genome sequence, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract: Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.
Published: 2017

4. Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription

Author: Marenne, Gaëlle, Hendricks, Audrey E., Perdikari, Aliki, Bounds, Rebecca, Payne, Felicity, Keogh, Julia M., Lelliott, Christopher J., Henning, Elana, Pathan, Saad, Ashford, Sofie, Bochukova, Elena G., Mistry, Vanisha, Daly, Allan, Hayward, Caroline, Wareham, Nicholas J., O’Rahilly, Stephen, Langenberg, Claudia, Wheeler, Eleanor, Zeggini, Eleftheria, Farooqi, I. Sadaf, and Barroso, Inês
Published: 2020
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5. The Genetic Links to Anxiety and Depression (GLAD) Study: Online recruitment into the largest recontactable study of depression and anxiety

Author: Davies, Molly R., Kalsi, Gursharan, Armour, Chérie, Jones, Ian R., McIntosh, Andrew M., Smith, Daniel J., Walters, James T.R., Bradley, John R., Kingston, Nathalie, Ashford, Sofie, Beange, Ioana, Brailean, Anamaria, Cleare, Anthony J., Coleman, Jonathan R.I., Curtis, Charles J., Curzons, Susannah C.B., Davis, Katrina A.S., Dowey, Le Roy C., Gault, Victor A., Goldsmith, Kimberley A., Bennett, Megan Hammond, Hirose, Yoriko, Hotopf, Matthew, Hübel, Christopher, Kanz, Carola, Leng, Jennifer, Lyall, Donald M., Mason, Bethany D., McAtarsney-Kovacs, Monika, Monssen, Dina, Moulton, Alexei, Ovington, Nigel, Palaiologou, Elisavet, Pariante, Carmine M., Parikh, Shivani, Peel, Alicia J., Price, Ruth K., Rimes, Katharine A., Rogers, Henry C., Sambrook, Jennifer, Skelton, Megan, Spaul, Anna, Suarez, Eddy L.A., Sykes, Bronte L., Thomas, Keith G., Young, Allan H., Vassos, Evangelos, Veale, David, White, Katie M., Wingrove, Janet, Eley, Thalia C., and Breen, Gerome
Published: 2019
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6. SMIM1 absence is associated with reduced energy expenditure and excess weight

Author: Banasik, Karina, Bay, Jakob, Boldsen, Jens Kjærgaard, Brodersen, Thorsten, Brunak, Søren, Burgdorf, Kristoffer, Chalmer, Mona Ameri, Didriksen, Maria, Dinh, Khoa Manh, Dowsett, Joseph, Erikstrup, Christian, Feenstra, Bjarke, Geller, Frank, Gudbjartsson, Daniel, Hansen, Thomas Folkmann, Hindhede, Lotte, Hjalgrim, Henrik, Jacobsen, Rikke Louise, Jemec, Gregor, Jensen, Bitten Aagaard, Kaspersen, Katrine, Kjerulff, Bertram Dalskov, Kogelman, Lisette, Hørup Larsen, Margit Anita, Louloudis, Ioannis, Lundgaard, Agnete, Susan, Mikkelsen, Christina, Nissen, Ioanna, Nyegaard, Mette, Ostrowski, Sisse Rye, Pedersen, Ole Birger, Henriksen, Alexander Pil, Rohde, Palle Duun, Rostgaard, Klaus, Schwinn, Michael, Stefansson, Kari, Stefánsson, Hreinn, Sørensen, Erik, þorsteinsdóttir, Unnur, Thørner, Lise Wegner, Bruun, Mie Topholm, Ullum, Henrik, Werge, Thomas, Westergaard, David, Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian’an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Katie Chan, Kei Hang, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Loz, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V.R., Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P., Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Southam, Lorraine, Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J.L., Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J.C., Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M. Arfan, Johnson, W. Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R.H.J., Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, Van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Goncalo R., Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Ida Chen, Yii-Der, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, Janaka de Silva, H., Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J. Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L.R., Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J.F., Magnusson, Patrik K.E., Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P. Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I.A., Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E. Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G.M., Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C.J., Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., Barroso, Inês, Stefanucci, Luca, Moslemi, Camous, Tomé, Ana R., Virtue, Samuel, Bidault, Guillaume, Gleadall, Nicholas S., Watson, Laura P.E., Kwa, Jing E., Burden, Frances, Farrow, Samantha, Võsa, Urmo, Burling, Keith, Walker, Lindsay, Ord, John, Barker, Peter, Warner, James, Frary, Amy, Renhstrom, Karola, Ashford, Sofie E., Piper, Jo, Biggs, Gail, Erber, Wendy N., Hoffman, Gary J., Schoenmakers, Nadia, Rieneck, Klaus, Dziegiel, Morten H., Azzu, Vian, Vacca, Michele, Aparicio, Hugo Javier, Hui, Qin, Cho, Kelly, Sun, Yan V., Wilson, Peter W., Bayraktar, Omer A., Vidal-Puig, Antonio, Ostrowski, Sisse R., Astle, William J., Olsson, Martin L., Storry, Jill R., Pedersen, Ole B., Ouwehand, Willem H., Chatterjee, Krishna, Vuckovic, Dragana, and Frontini, Mattia
Published: 2024
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7. A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss

Author: Stritt, Simon, Nurden, Paquita, Turro, Ernest, Greene, Daniel, Jansen, Sjoert B., Westbury, Sarah K., Petersen, Romina, Astle, William J., Marlin, Sandrine, Bariana, Tadbir K., Kostadima, Myrto, Lentaigne, Claire, Maiwald, Stephanie, Papadia, Sofia, Kelly, Anne M., Stephens, Jonathan C., Penkett, Christopher J., Ashford, Sofie, Tuna, Salih, Austin, Steve, Bakchoul, Tamam, Collins, Peter, Favier, Rémi, Lambert, Michele P., Mathias, Mary, Millar, Carolyn M., Mapeta, Rutendo, Perry, David J., Schulman, Sol, Simeoni, Ilenia, Thys, Chantal, Gomez, Keith, Erber, Wendy N., Stirrups, Kathleen, Rendon, Augusto, Bradley, John R., van Geet, Chris, Raymond, F.Lucy, Laffan, Michael A., Nurden, Alan T., Nieswandt, Bernhard, Richardson, Sylvia, Freson, Kathleen, Ouwehand, Willem H., and Mumford, Andrew D.
Published: 2016
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8. Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension

Author: Hadinnapola, Charaka, Bleda, Marta, Haimel, Matthias, Screaton, Nicholas, Swift, Andrew, Dorfmüller, Peter, Preston, Stephen D., Southwood, Mark, Hernandez-Sanchez, Jules, Martin, Jennifer, Treacy, Carmen, Yates, Katherine, Bogaard, Harm, Church, Colin, Coghlan, Gerry, Condliffe, Robin, Corris, Paul A., Gibbs, Simon, Girerd, Barbara, Holden, Simon, Humbert, Marc, Kiely, David G., Lawrie, Allan, Machado, Rajiv, MacKenzie Ross, Robert, Moledina, Shahin, Montani, David, Newnham, Michael, Peacock, Andrew, Pepke-Zaba, Joanna, Rayner-Matthews, Paula, Shamardina, Olga, Soubrier, Florent, Southgate, Laura, Suntharalingam, Jay, Toshner, Mark, Trembath, Richard, Noordegraaf, Anton Vonk, Wilkins, Martin R., Wort, Stephen J., Wharton, John, Gräf, Stefan, Morrell, Nicholas W., Aitman, Timothy, Bennett, David, Caulfield, Mark, Chinnery, Patrick, Gale, Daniel, Koziell, Ania, Kuijpers, Taco W, Laffan, Michael A, Maher, Eamonn, Markus, Hugh S, Ouwehand, Willem H, Perry, David, Raymond, F Lucy, Roberts, Irene, Smith, Kenneth, Thrasher, Adrian, Watkins, Hugh, Williamson, Catherine, Woods, Geoffrey, Ashford, Sofie, Bradley, John R, Fletcher, Debra, Hammerton, Tracey, James, Roger, Kingston, Nathalie, Ouwehand, Willem H, Penkett, Christopher J, Raymond, F Lucy, Stirrups, Kathleen, Veltman, Marijke, Young, Tim, Ashford, Sofie, Brown, Matthew, Clements-Brod, Naomi, Davis, John, Dewhurst, Eleanor, Erwood, Marie, Frary, Amy, Linger, Rachel, Papadia, Sofia, Rehnstrom, Karola, Stark, Hannah, Allsup, David, Austin, Steve, Bakchoul, Tamam, Bariana, Tadbir K, Bolton-Maggs, Paula, Chalmers, Elizabeth, Collins, Peter, Erber, Wendy N, Everington, Tamara, Favier, Remi, Freson, Kathleen, Furie, Bruce, Gattens, Michael, Gomez, Keith, Greene, Daniel, Greinacher, Andreas, Hart, Daniel, Heemskerk, Johan WM, Henskens, Yvonne, Kazmi, Rashid, Keeling, David, Kelly, Anne M, Laffan, Michael A, Lambert, Michele P, Lentaigne, Claire, Liesner, Ri, Mangles, Sarah, Mathias, Mary, Millar, Carolyn M, Mumford, Andrew, Nurden, Paquita, Ouwehand, Willem H, Papadia, Sofia, Payne, Jeanette, Pasi, John, Perry, David J, Peerlinck, Kathelijne, Richards, Michael, Rondina, Matthew, Roughley, Catherine, Schulman, Sol, Schulze, Harald, Scully, Marie, Sivapalaratnam, Suthesh, Tait, R Campbell, Talks, Kate, Thachil, Jecko, Turro, Ernest, Toh, Cheng-Hock, Van Geet, Chris, De Vries, Minka, Warner, Timothy Q, Westbury, Sarah, Furnell, Abigail, Mapeta, Rutendo, Simeoni, Ilenia, Staines, Simon, Stephens, Jonathan, Stirrups, Kathleen, Whitehorn, Deborah, Watt, Christopher, Attwood, Antony, Daugherty, Louise, Deevi, Sri VV, Halmagyi, Csaba, Hu, Fengyuan, James, Roger, Matser, Vera, Meacham, Stuart, Megy, Karyn, Penkett, Christopher J, Stirrups, Kathleen, Titterton, Catherine, Tuna, Salih, Yu, Ping, von Ziegenweldt, Julie, Astle, William, Carss, Keren, Greene, Daniel, Lango-Allen, Hana, Turro, Ernest, Astle, William, Greene, Daniel, Richardson, Sylvia, Turro, Ernest, Calleja, Paul, Rankin, Stuart, Turek, Wojciech, Bryson, Christine, Anderson, Julie, Fletcher, Debra, McJannet, Coleen, Stock, Sophie, Young, Tim, Wassmer, Evangeline, Sohal, Aman, Santra, Saikat, Vogt, Julie, Chitre, Manali, Krishnakumar, Deepa, Ambegaonkar, Gautum, Maw, Anna, Armstrong, Ruth, Park, Soo-Mi, Mehta, Sarju, Paterson, Joan, Carmichael, Jenny, Allen, Louise, Hensiek, Anke, Firth, Helen, Stein, Penelope, Deegan, Patrick, Doffinger, Rainer, Parker, Alasdair, Bitner-Glindzicz, Maria, Scott, Richard, Hurst, Jane, Rosser, Elisabeth, Lees, Melissa, Clement, Emma, Henderson, Robert, Thompson, Dorothy, Gardham, Alice, Gissen, Paul, Josifova, Dragana, Thomas, Ellen, Patch, Chris, Deshpande, Charu, Flinter, Frances, Holder, Muriel, Canham, Natalie, Wakeling, Emma, Holder, Susan, Ghali, Neeti, Brady, Angie, Clowes, Virginia, MacLaren, Robert, Webster, Andrew, Moore, Anthony, Arno, Gavin, Michaelides, Michel, Rankin, Julia, Kurian, Manju, Murphy, Elaine, Carss, Keren, Sanchis-Juan, Alba, Erwood, Marie, Dewhurst, Eleanor, Grozeva, Detelina, Raymond, F Lucy, Reid, Evan, Woods, Geoff, Tischkowitz, Marc, Sandford, Richard, Ali, Sonia, Creaser-Myers, Amanda, Cookson, Victoria, DaCosta, Rosa, Dormand, Natalie, Ghataorhe, Pavandeep K, Greenhalgh, Alan, Huis in’t Veld, Anna, Kennedy, Fiona, Mackenzie Ross, Rob, Masati, Larahmie, Meehan, Sharon, Othman, Shokri, Pollock, Val, Polwarth, Gary, Rhodes, Christopher J, Rue-Albrecht, Kevin, Schotte, Gwen, Shipley, Debbie, Tan, Yvonne, Wanjiku, Ivy, Wort, John, Smith, Kenneth, Kuijpers, Taco, Thrasher, Adrian, Thaventhiran, James, Brown, Matthew, Lango Allen, Hana, Simeoni, Ilenia, Staples, Emily, Samarghitean, Crina, Alachkar, Hana, Antrobus, Richard, Arumugakani, Gururaj, Bacchelli, Chiara, Baxendale, Helen, Bethune, Claire, Bibi, Shahnaz, Booth, Claire, Browning, Michael, Burns, Siobhan, Chandra, Anita, Cooper, Nichola, Davies, Sophie, Devlin, Lisa, Doffinger, Rainer, Drewe, Elizabeth, Edgar, David, Egner, William, Ghurye, Rohit, Gilmour, Kimberley, Goddard, Sarah, Gordins, Pavel, Grigoriadou, Sofia, Hackett, Scott, Hague, Rosie, Hayman, Grant, Herwadkar, Archana, Huissoon, Aarnoud, Jolles, Stephen, Kelleher, Peter, Kumararatne, Dinakantha, Lear, Sara, Longhurst, Hilary, Lorenzo, Lorena, Maimaris, Jesmeen, Manson, Ania, McDermott, Elizabeth, Murng, Sai, Nejentsev, Sergey, Noorani, Sadia, Oksenhendler, Eric, Ponsford, Mark, Qasim, Waseem, Quinti, Isabella, Richter, Alex, Sargur, Ravishankar, Savic, Sinisa, Seneviratne, Suranjith, Sewell, Carrock, Stauss, Hans, Thomas, Moira, Welch, Steve, Willcocks, Lisa, Yeatman, Nigel, and Yong, Patrick
Published: 2017
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9. Common genetic variation drives molecular heterogeneity in human iPSCs

Author: Kilpinen, Helena, Goncalves, Angela, Leha, Andreas, Afzal, Vackar, Alasoo, Kaur, Ashford, Sofie, Bala, Sendu, Bensaddek, Dalila, Casale, Francesco Paolo, Culley, Oliver J., Danecek, Petr, Faulconbridge, Adam, Harrison, Peter W., Kathuria, Annie, McCarthy, Davis, McCarthy, Shane A., Meleckyte, Ruta, Memari, Yasin, Moens, Nathalie, Soares, Filipa, Mann, Alice, Streeter, Ian, Agu, Chukwuma A., Alderton, Alex, Nelson, Rachel, Harper, Sarah, Patel, Minal, White, Alistair, Patel, Sharad R., Clarke, Laura, Halai, Reena, Kirton, Christopher M., Kolb-Kokocinski, Anja, Beales, Philip, Birney, Ewan, Danovi, Davide, Lamond, Angus I., Ouwehand, Willem H., Vallier, Ludovic, Watt, Fiona M., Durbin, Richard, Stegle, Oliver, and Gaffney, Daniel J.
Subjects: Genetic variation -- Health aspects, Stem cells -- Genetic aspects -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 546% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells., Author(s): Helena Kilpinen [1]; Angela Goncalves [2]; Andreas Leha [2]; Vackar Afzal [3]; Kaur Alasoo [2]; Sofie Ashford [4]; Sendu Bala [2]; Dalila Bensaddek [3]; Francesco Paolo Casale [1]; Oliver [...]
Published: 2017
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10. GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Author: Dixon, Peter H., Levine, Adam P., Cebola, Inês, Chan, Melanie M. Y., Amin, Aliya S., Aich, Anshul, Mozere, Monika, Maude, Hannah, Mitchell, Alice L., Zhang, Jun, Adlard, Julian, Ahmed, Munaza, Aitman, Tim, Alachkar, Hana, Allsup, David, Almeida-King, Jeff, Ancliff, Philip, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Ashford, Sofie, Astle, William, Attwood, Anthony, Babbs, Chris, Bakchoul, Tamam, Bariana, Tadbir, Barwell, Julian, Bennett, David, Bentley, David, Bierzynska, Agnieszka, Biss, Tina, Bleda, Marta, Bogaard, Harm, Bourne, Christian, Boyce, Sara, Bradley, John, Breen, Gerome, Brennan, Paul, Brewer, Carole, Brown, Matthew, Browning, Michael, Buchan, Rachel, Buckland, Matthew, Bueser, Teofila, Burns, Siobhan, Burren, Oliver, Calleja, Paul, Carr-White, Gerald, Carss, Keren, Casey, Ruth, Caulfield, Mark, Chambers, John, Chambers, Jennifer, Cheng, Floria, Chinnery, Patrick F., Christian, Martin, Church, Colin, Brod, Naomi Clements, Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor, Collins, Janine, Collins, Peter, Colombo, Camilla, Condliffe, Robin, Cook, Stuart, Cook, Terry, Cooper, Nichola, Corris, Paul, Crisp-Hihn, Abigail, Curry, Nicola, Danesino, Cesare, Daniels, Matthew, Daugherty, Louise, Davis, John, Deevi, Sri V. V., Dent, Timothy, Dewhurst, Eleanor, Dixon, Peter, Downes, Kate, Drazyk, Anna, Drewe, Elizabeth, Dutt, Tina, Edgar, David, Edwards, Karen, Egner, William, Erber, Wendy, Erwood, Marie, Estiu, Maria C., Evans, Gillian, Evans, Dafydd Gareth, Everington, Tamara, Eyries, Mélanie, Favier, Remi, Fletcher, Debra, Fox, James, Frary, Amy, French, Courtney, Freson, Kathleen, Frontini, Mattia, Gale, Daniel, Gall, Henning, Geoghegan, Claire, Gerighty, Terry, Ghio, Stefano, Ghofrani, Hossein-Ardeschir, Gibbs, Simon, Gilmour, Kimberley, Girerd, Barbara, Goddard, Sarah, Gomez, Keith, Gordins, Pavels, Gosal, David, Gräf, Stefan, Grassi, Luigi, Greene, Daniel, Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip, Grigoriadou, Sofia, Grocock, Russell, Grozeva, Detelina, Hackett, Scott, Hadinnapola, Charaka, Hague, William, Haimel, Matthias, Hall, Matthew, Hanson, Helen, Harkness, Kirsty, Harper, Andrew, Harris, Claire, Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Henderson, Alex, Hoffmann, Jonathan, Horvath, Rita, Houweling, Arjan, Howard, Luke, Hu, Fengyuan, Hudson, Gavin, Hughes, Joseph, Huissoon, Aarnoud, Humbert, Marc, Humphray, Sean, Hunter, Sarah, Hurles, Matthew, Izatt, Louise, James, Roger, Johnson, Sally, Jolles, Stephen, Jolley, Jennifer, Jurkute, Neringa, Kasanicki, Mary, Kazkaz, Hanadi, Kazmi, Rashid, Kelleher, Peter, Kiely, David, Kingston, Nathalie, Klima, Robert, Kostadima, Myrto, Kovacs, Gabor, Koziell, Ania, Kreuzhuber, Roman, Kuijpers, Taco, Kumar, Ajith, Kumararatne, Dinakantha, Kuria, Manju, Laffa, Michael, Lalloo, Fiona, Lamber, Michele, Alle, Hana Lango, Lawrie, Allan, Layton, Mark, Lentaigne, Claire, Levine, Adam, Linger, Rachel, Longhurst, Hilary, Louka, Eleni, Ross, Robert MacKenzie, Madan, Bella, Maher, Eamonn, Maimaris, Jesmeen, Mangles, Sarah, Mapeta, Rutendo, Marchbank, Kevin, Marks, Stephen, Markus, Hugh S., Marshall, Andrew, Martin, Jennifer, Mathias, Mary, Matthews, Emma, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark, Meacham, Stuart, Mead, Adam, Megy, Karyn, Mehta, Sarju, Michaelides, Michel, Millar, Carolyn, Moledina, Shahin, Montani, David, Moor, Tony, Morrell, Nicholas, Muir, Keith, Mumford, Andrew, Newnham, Michael, O'Sullivan, Jennifer, Obaji, Samya, Okoli, Steven, Olschewski, Andrea, Olschewski, Horst, Ong, Kai Ren, Ormondroy, Elizabeth, Ouwehan, Willem, Papadi, Sofia, Park, Soo-Mi, Parry, David, Paterson, Joan, Peacock, Andrew, Peden, John, Peerlinck, Kathelijne, Penkett, Christopher, Pepke-Zaba, Joanna, Petersen, Romina, Pyle, Angela, Rankin, Stuart, Rao, Anupama, Raymond, F. Lucy, Rayner-Matthew, Paula, Rees, Christine, Rendon, Augusto, Renton, Tara, Rice, Andrew, Richardson, Sylvia, Richter, Alex, Roberts, Irene, Roughley, Catherine, Roy, Noemi, Sadeghi-Alavijeh, Omid, Saleem, Moin, Samani, Nilesh, Sanchis-Juan, Alba, Sargur, Ravishankar, Satchell, Simon, Savic, Sinisa, Scelsi, Laura, Schulman, Sol, Scully, Marie, Searle, Claire, Seeger, Werner, Sewell, Carrock, Seyres, Denis, Shapiro, Susie, Sharmardina, Olga, Shtoyerman, Rakefet, Sibson, Keith, Side, Lucy, Simeoni, Ilenia, Simpson, Michael, Sivapalaratnam, Suthesh, Skytte, Anne-Bine, Smith, Katherine, Smith, Kenneth G. C., Snape, Katie, Soubrier, Florent, Staines, Simon, Staples, Emily, Stark, Hannah, Stephens, Jonathan, Stirrups, Kathleen, Stock, Sophie, Suntharalingam, Jay, Swietlik, Emilia, Tait, R. Campbell, Talks, Kate, Tan, Rhea, Thaventhiran, James, Themistocleous, Andreas, Thomas, Moira, Thomson, Kate, Thrasher, Adrian, Thys, Chantal, Tischkowitz, Marc, Titterton, Catherine, Toh, Cheng-Hock, Toshner, Mark, Traylor, Matthew, Treacy, Carmen, Trembath, Richard, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Vale, Tom, Van Geet, Chris, Van Zuydam, Natalie, Vazquez-Lopez, Marta, von Ziegenweidt, Julie, Noordegraaf, Anton Vonk, Waisfisz, Quintin, Walker, Suellen, Ware, James, Watkins, Hugh, Watt, Christopher, Webster, Andrew, Wei, Wei, Welch, Steven, Wessels, Julie, Westbury, Sarah, Westwood, John-Paul, Wharton, John, Whitehorn, Deborah, Whitworth, James, Wilkins, Martin R., Wong, Edwin, Wood, Nicholas, Wood, Yvette, Woods, Geoff, Woodward, Emma, Wort, Stephen, Worth, Austen, Yates, Katherine, Yong, Patrick, Young, Tim, Yu, Ping, Yu-Wai-Man, Patrick, Ambrose, J. C., Arumugam, P., Bevers, R., Bleda, M., Boardman-Pretty, F., Boustred, C. R., Brittain, H., Brown, M. A., Caulfield, M. J., Chan, G. C., Fowler, T., Giess, A., Hamblin, A., Henderson, S., Hubbard, T. J. P., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Kousathanas, A., Lahnstein, L., Leigh, S. E. A., Leong, I. U. S., Lopez, F. J., Maleady-Crowe, F., McEntagart, M., Minneci, F., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A. C., O'Donovan, P., Odhams, C. A., Patch, C., Perez-Gil, D., Pereira, M. B., Pullinger, J., Rahim, T., Rendon, A., Rogers, T., Savage, K., Sawant, K., Scott, R. H., Siddiq, A., Sieghart, A., Smith, S. C., Sosinsky, A., Stuckey, A., Tanguy, M., Taylor Tavares, A. L., Thomas, E. R. A., Thompson, S. R., Tucci, A., Welland, M. J., Williams, E., Witkowska, K., Wood, S. M., Chambers, Jenny, Syngelaki, Argyro, Donnelly, Jennifer, Cooley, Sharon, Geary, Michael, Nicolaides, Kypros, Thorsell, Malin, Hague, William M., Estiu, Maria Cecilia, Marschall, Hanns-Ulrich, Gale, Daniel P., Williamson, Catherine, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Human genetics, ACS - Atherosclerosis & ischemic syndromes, Pediatrics, Foundation for the National Institutes of Health (FNIH), The Academy of Medical Sciences, British Heart Foundation, Imperial College Healthcare NHS Trust- BRC Funding, Paediatric Infectious Diseases / Rheumatology / Immunology, and ARD - Amsterdam Reproduction and Development
Subjects: VARIANT, LOCI, INTEGRATIVE ANALYSIS, General Physics and Astronomy, Cholestasis, Intrahepatic, TRIGLYCERIDE LEVELS, DISEASE, General Biochemistry, Genetics and Molecular Biology, Bile Acids and Salts, Pregnancy, Humans, MUTATION, Science & Technology, Multidisciplinary, Genomics England Research Consortium Collaborators, Infant, Newborn, NIHR BioResource, General Chemistry, GLUCOCORTICOID-RECEPTOR, Multidisciplinary Sciences, ALKALINE SPHINGOMYELINASE, Pregnancy Complications, INSIGHTS, Science & Technology - Other Topics, Premature Birth, Female, FASTING GLUCOSE, Genome-Wide Association Study
Abstract: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility. ispartof: NATURE COMMUNICATIONS vol:13 issue:1 ispartof: location:England status: published
Published: 2022

11. Loss of function variant in SMIM1 is associated with reduced energy expenditure and weight gain

Author: Frontini, Mattia, primary, Stefanucci, Luca, additional, Moslemi, Camous, additional, Tome, Ana, additional, Virtue, Samuel, additional, Gleadall, Nicholas, additional, Watson, Laura, additional, Kwa, Jing, additional, Burden, Frances, additional, Farrow, Samantha, additional, Chen, Ji, additional, Võsa, Urmo, additional, Burling, Keith, additional, Baker, Peter, additional, Warner, James, additional, Frary, Amy, additional, Rehnstrom, Karola, additional, Ashford, Sofie, additional, Piper, Jo, additional, Biggs, Gail, additional, Erber, Wendy, additional, Hoffman, Gary, additional, Schoenmakers, Nadia, additional, Erikstrup, Christian, additional, Rieneck, Klaus, additional, Dziegiel, Morten, additional, Ullum, Henrik, additional, Azzu, Vian, additional, Vacca, Michele, additional, Bayraktar, Omer Ali, additional, Vidal-Puig, Antonio, additional, Ostrowski, Sisse, additional, Astle, William, additional, Olsson, Martin L., additional, Storry, Jill R., additional, Pedersen, Ole, additional, Ouwehand, Willem, additional, Chatterjee, Krishna, additional, and Vuckovic, Dragana, additional
Published: 2022
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12. Whole-genome sequencing of patients with rare diseases in a national health system

Author: Turro, Ernest, Astle, William J., Megy, Karyn, Gräf, Stefan, Greene, Daniel, Shamardina, Olga, Allen, Hana Lango, Sanchis-Juan, Alba, Frontini, Mattia, Thys, Chantal, Stephens, Jonathan, Mapeta, Rutendo, Burren, Oliver S., Downes, Kate, Haimel, Matthias, Tuna, Salih, Deevi, Sri V.V., Aitman, Timothy J., Bennett, David L., Calleja, Paul, Carss, Keren, Caulfield, Mark J., Chinnery, Patrick F., Dixon, Peter H., Gale, Daniel P., James, Roger, Koziell, Ania, Laffan, Michael A., Levine, Adam P., Maher, Eamonn R., Markus, Hugh S., Morales, Joannella, Morrell, Nicholas W., Mumford, Andrew D., Ormondroyd, Elizabeth, Rankin, Stuart, Rendon, Augusto, Richardson, Sylvia, Roberts, Irene, Roy, Noemi B.A., Saleem, Moin A., Smith, Kenneth G.C., Stark, Hannah, Tan, Rhea Y.Y., Themistocleous, Andreas C., Thrasher, Adrian J., Watkins, Hugh, Webster, Andrew R., Wilkins, Martin R., Williamson, Catherine, Whitworth, James, Humphray, Sean, Bentley, David R., Abbs, Stephen, Abulhoul, Lara, Adlard, Julian, Ahmed, Munaza, Alachkar, Hana, Allsup, David J., Almeida-King, Jeff, Ancliff, Philip, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Ashford, Sofie, Attwood, Anthony, Aurora, Paul, Babbs, Christian, Bacchelli, Chiara, Bakchoul, Tamam, Banka, Siddharth, Bariana, Tadbir, Barwell, Julian, Batista, Joana, Baxendale, Helen E., Beales, Phil L., Bierzynska, Agnieszka, Biss, Tina, Bitner-Glindzicz, Maria A.K., Black, Graeme C., Bleda, Marta, Blesneac, Iulia, Bockenhauer, Detlef, Bogaard, Harm, Bourne, Christian J., Boyce, Sara, Bradley, John R., Bragin, Eugene, Breen, Gerome, Brennan, Paul, Brewer, Carole, Brown, Matthew, Browning, Andrew C., Browning, Michael J., Buchan, Rachel J., Buckland, Matthew S., Bueser, Teofila, Diz, Carmen Bugarin, Burn, John, Burns, Siobhan O., Burrows, Nigel, Campbell, Carolyn, Carr-White, Gerald, Casey, Ruth, Chambers, Jenny, Chambers, John, Chan, Melanie M.Y., Cheah, Calvin, Cheng, Floria, Chitre, Manali, Christian, Martin T., Church, Colin, Clayton-Smith, Jill, Cleary, Maureen, Brod, Naomi Clements, Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor R.P., Collins, Janine, Collins, Peter W., Colombo, Camilla, Compton, Cecilia J., Condliffe, Robin, Cook, Stuart, Cook, H. Terence, Cooper, Nichola, Corris, Paul A A., Furnell, Abigail, Cunningham, Fiona, Curry, Nicola S., Cutler, Antony J., Daniels, Matthew J., Dattani, Mehul, Daugherty, Louise C., Davis, John, De Soyza, Anthony, Dent, Timothy, Deshpande, Charu, Dewhurst, Eleanor F., Douzgou, Sofia, Drazyk, Anna M., Drewe, Elizabeth, Duarte, Daniel, Dutt, Tina, Edgar, J. David M., Edwards, Karen, Egner, William, Ekani, Melanie N., Elliott, Perry, Erber, Wendy N., Erwood, Marie, Estiu, Maria C., Evans, Dafydd Gareth, Evans, Gillian, Everington, Tamara, Eyries, Mélanie, Fassihi, Hiva, Favier, Remi, Findhammer, Jack, Fletcher, Debra, Flinter, Frances A., Floto, R. Andres, Fowler, Tom, Fox, James, Frary, Amy J., French, Courtney E., Freson, Kathleen, Gall, Henning, Ganesan, Vijeya, Gattens, Michael, Geoghegan, Claire, Gerighty, Terence S.A., Gharavi, Ali G., Ghio, Stefano, Ghofrani, Hossein Ardeschir, Gibbs, J. Simon R., Gibson, Kate, Gilmour, Kimberly C., Girerd, Barbara, Gleadall, Nicholas S., Goddard, Sarah, Goldstein, David B., Gomez, Keith, Gordins, Pavels, Gosal, David, Graham, Jodie, Grassi, Luigi, Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip, Grigoriadou, Sofia, Grocock, Russell J., Grozeva, Detelina, Gurnell, Mark, Hackett, Scott, Hadinnapola, Charaka, Hague, William M., Hague, Rosie, Hall, Matthew, Hanson, Helen L., Haque, Eshika, Harkness, Kirsty, Harper, Andrew R., Harris, Claire L L., Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Henderson, Alex, Herwadkar, Archana, Hoffman, Jonathan, Holden, Simon, Horvath, Rita, Houlden, Henry, Houweling, Arjan C C., Howard, Luke S., Hu, Fengyuan, Hudson, Gavin, Hughes, Joseph, Huissoon, Aarnoud P., Humbert, Marc, Hunter, Sarah, Hurles, Matthew, Irving, Melita, Izatt, Louise, Johnson, Sally A., Jolles, Stephen, Jolley, Jennifer, Josifova, Dragana, Jurkute, Neringa, Karten, Tim, Karten, Johannes, Kasanicki, Mary A., Kazkaz, Hanadi, Kazmi, Rashid, Kelleher, Peter, Kelly, Anne M., Kelsall, Wilf, Kempster, Carly, Kiely, David G., Kingston, Nathalie, Klima, Robert, Koelling, Nils, Kostadima, Myrto, Kovacs, Gabor, Kreuzhuber, Roman, Kuijpers, Taco W., Kumar, Ajith, Kumararatne, Dinakantha, Kurian, Manju A., Lalloo, Fiona, Lambert, Michele, Lawrie, Allan, Layton, D. Mark, Lench, Nick, Lentaigne, Claire, Lester, Tracy, Linger, Rachel, Longhurst, Hilary, Lorenzo, Lorena E., Louka, Eleni, Lyons, Paul A., Machado, Rajiv D., MacKenzie Ross, Robert V., Madan, Bella, Maimaris, Jesmeen, Malka, Samantha, Mangles, Sarah, Marchbank, Kevin J., Marks, Stephen, Marschall, Hanns Ulrich, Marshall, Andrew, Martin, Jennifer, Mathias, Mary, Matthews, Emma, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark I., McKinney, Harriet, McMahon, Aoife, Meacham, Stuart, Mead, Adam J., Castello, Ignacio Medina, Mehta, Sarju G G., Michaelides, Michel, Millar, Carolyn, Mohammed, Shehla N., Moledina, Shahin, Montani, David, Moore, Anthony T., Mozere, Monika, Muir, Keith W., Nemeth, Andrea H., Newman, William G., Newnham, Michael, Noorani, Sadia, Nurden, Paquita, O’Sullivan, Jennifer, Obaji, Samya, Odhams, Chris, Okoli, Steven, Olschewski, Andrea, Olschewski, Horst, Ong, Kai Ren, Oram, S. Helen, Ouwehand, Willem H., Palles, Claire, Papadia, Sofia, Park, Soo Mi, Parry, David, Patel, Smita, Paterson, Joan, Peacock, Andrew, Pearce, Simon H H., Peden, John, Peerlinck, Kathelijne, Penkett, Christopher J., Pepke-Zaba, Joanna, Petersen, Romina, Pilkington, Clarissa, Poole, Kenneth E.S., Prathalingam, Radhika, Psaila, Bethan, Pyle, Angela, Quinton, Richard, Rahman, Shamima, Rao, Anupama, Raymond, F. Lucy, Rayner-Matthews, Paula J., Rees, Christine, Renton, Tara, Rhodes, Christopher J., Rice, Andrew S.C., Richter, Alex, Robert, Leema, Rogers, Anthony, Rose, Sarah J., Ross-Russell, Robert, Roughley, Catherine, Roy, Noemi B. A, Ruddy, Deborah M., Sadeghi-Alavijeh, Omid, Samani, Nilesh, Samarghitean, Crina, Sargur, Ravishankar B., Sarkany, Robert N., Satchell, Simon, Savic, Sinisa, Sayer, John A., Sayer, Genevieve, Scelsi, Laura, Schaefer, Andrew M., Schulman, Sol, Scott, Richard, Scully, Marie, Searle, Claire, Seeger, Werner, Sen, Arjune, Sewell, W. A.Carrock, Seyres, Denis, Shah, Neil, Shapiro, Susan E., Shaw, Adam C., Short, Patrick J., Sibson, Keith, Side, Lucy, Simeoni, Ilenia, Simpson, Michael A A., Sims, Matthew C., Sivapalaratnam, Suthesh, Smedley, Damian, Smith, Katherine R., Snape, Katie, Soranzo, Nicole, Soubrier, Florent, Southgate, Laura, Spasic-Boskovic, Olivera, Staines, Simon, Staples, Emily, Steward, Charles, Stirrups, Kathleen E., Stuckey, Alex, Suntharalingam, Jay, Swietlik, Emilia M., Syrris, Petros, Tait, R. Campbell, Talks, Kate, Tate, Katie, Taylor, John M., Taylor, Jenny C., Thaventhiran, James E., Thomas, Ellen, Thomas, David, Thomas, Moira J., Thomas, Patrick, Thomson, Kate, Threadgold, Glen, Tilly, Tobias, Tischkowitz, Marc, Titterton, Catherine, Todd, John A., Toh, Cheng Hock, Tolhuis, Bas, Tomlinson, Ian P., Toshner, Mark, Traylor, Matthew, Treacy, Carmen, Treadaway, Paul, Trembath, Richard, Turek, Wojciech, Twiss, Philip, Vale, Tom, Geet, Chris Van, Zuydam, Natalie van, Vandekuilen, Maarten, Vandersteen, Anthony M., Vazquez-Lopez, Marta, von Ziegenweidt, Julie, Vonk Noordegraaf, Anton, Wagner, Annette, Waisfisz, Quinten, Walker, Suellen M., Walker, Neil, Walter, Klaudia, Ware, James S., Watt, Christopher, Wedderburn, Lucy, Wei, Wei, Welch, Steven B., Wessels, Julie, Westbury, Sarah K., Westwood, John Paul, Wharton, John, Whitehorn, Deborah, Wilkie, Andrew O. M, Wilson, Brian T., Wong, Edwin K.S., Wood, Nicholas, Wood, Yvette, Woods, Christopher Geoffrey, Woodward, Emma R R., Wort, Stephen J., Worth, Austen, Wright, Michael, Yates, Katherine, Yong, Patrick F.K., Young, Timothy, Yu, Ping, Yu-Wai-Man, Patrick, Zlamalova, Eliska, University of Cambridge [UK] (CAM), John Wyeth & Brother Limited, Medical Research Council (MRC), Wellcome Trust, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Human genetics, ACS - Atherosclerosis & ischemic syndromes, Landsteiner Laboratory, Paediatric Infectious Diseases / Rheumatology / Immunology, ARD - Amsterdam Reproduction and Development, and Project, NIHR BioResource for the 100,000 Genomes
Subjects: 0301 basic medicine, Erythrocytes, Internationality, Databases, Factual, National Health Programs, [SDV]Life Sciences [q-bio], Disease, VARIANTS, Genome, State Medicine, NIHR BioResource for the 100,000 Genomes Project, 0302 clinical medicine, Medicine, GATA1 Transcription Factor, Genetics, Multidisciplinary, Translational bioinformatics, ASSOCIATION, 3. Good health, Multidisciplinary Sciences, Phenotype, 030220 oncology & carcinogenesis, disease genetics, Medical genetics, Science & Technology - Other Topics, Receptors, Thrombopoietin, medicine.medical_specialty, General Science & Technology, Quantitative Trait Loci, Genomics, Computational biology, Biology, DIAGNOSIS, computational biology and bioinformatics, Actin-Related Protein 2-3 Complex, Article, LRBA, LINKS, 03 medical and health sciences, Rare Diseases, Humans, Alleles, Adaptor Proteins, Signal Transducing, Whole genome sequencing, National health, Science & Technology, Whole Genome Sequencing, MUTATIONS, business.industry, THROMBOCYTOPENIA, United Kingdom, MACROTHROMBOCYTOPENIA, genetics research, 030104 developmental biology, business, Rare disease
Abstract: Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
Published: 2021

13. LDL-cholesterol concentrations: a genome-wide association study

Author: Sandhu, Manjinder S, Waterworth, Dawn M, Debenham, Sally L, Wheeler, Eleanor, Papadakis, Konstantinos, Zhao, Jing Hua, Song, Kijoung, Yuan, Xin, Johnson, Toby, Ashford, Sofie, Inouye, Michael, Luben, Robert, Sims, Matthew, Hadley, David, McArdle, Wendy, Barter, Philip, Kesäniemi, Y Antero, Mahley, Robert W, McPherson, Ruth, Grundy, Scott M, Bingham, Sheila A, Khaw, Kay-Tee, Loos, Ruth JF, Waeber, Gérard, Barroso, Inês, Strachan, David P, Deloukas, Panagiotis, Vollenweider, Peter, Wareham, Nicholas J, and Mooser, Vincent
Published: 2008
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14. Bayesian Inference Associates Rare KDR Variants With Specific Phenotypes in Pulmonary Arterial Hypertension

Author: Swietlik, Emilia M., primary, Greene, Daniel, additional, Zhu, Na, additional, Megy, Karyn, additional, Cogliano, Marcella, additional, Rajaram, Smitha, additional, Pandya, Divya, additional, Tilly, Tobias, additional, Lutz, Katie A., additional, Welch, Carrie C.L., additional, Pauciulo, Michael W., additional, Southgate, Laura, additional, Martin, Jennifer M., additional, Treacy, Carmen M., additional, Penkett, Christopher J., additional, Stephens, Jonathan C., additional, Bogaard, Harm J., additional, Church, Colin, additional, Coghlan, Gerry, additional, Coleman, Anna W., additional, Condliffe, Robin, additional, Eichstaedt, Christina A., additional, Eyries, Mélanie, additional, Gall, Henning, additional, Ghio, Stefano, additional, Girerd, Barbara, additional, Grünig, Ekkehard, additional, Holden, Simon, additional, Howard, Luke, additional, Humbert, Marc, additional, Kiely, David G., additional, Kovacs, Gabor, additional, Lordan, Jim, additional, Machado, Rajiv D., additional, MacKenzie Ross, Robert V., additional, McCabe, Colm, additional, Moledina, Shahin, additional, Montani, David, additional, Olschewski, Horst, additional, Pepke-Zaba, Joanna, additional, Price, Laura, additional, Rhodes, Christopher J., additional, Seeger, Werner, additional, Soubrier, Florent, additional, Suntharalingam, Jay, additional, Toshner, Mark R., additional, Vonk Noordegraaf, Anton, additional, Wharton, John, additional, Wild, James M., additional, Wort, Stephen John, additional, Lawrie, Allan, additional, Wilkins, Martin R., additional, Trembath, Richard C., additional, Shen, Yufeng, additional, Chung, Wendy K., additional, Swift, Andrew J., additional, Nichols, William C., additional, Morrell, Nicholas W., additional, Gräf, Stefan, additional, Abbs, Stephen, additional, Abulhoul, Lara, additional, Adlard, Julian, additional, Ahmed, Munaza, additional, Aitman, Timothy J., additional, Alachkar, Hana, additional, Allsup, David J., additional, Ancliff, Philip, additional, Antrobus, Richard, additional, Armstrong, Ruth, additional, Arno, Gavin, additional, Ashford, Sofie, additional, Astle, William J., additional, Attwood, Anthony, additional, Aurora, Paul, additional, Babbs, Christian, additional, Bacchelli, Chiara, additional, Bakchoul, Tamam, additional, Banka, Siddharth, additional, Bariana, Tadbir, additional, Barwell, Julian, additional, Batista, Joana, additional, Baxendale, Helen E., additional, Beales, Phil L., additional, Bennett, David L., additional, Bierzynska, Agnieszka, additional, Biss, Tina, additional, Bitner-Glindzicz, Maria A.K., additional, Black, Graeme C., additional, Bleda, Marta, additional, Blesneac, Iulia, additional, Bockenhauer, Detlef, additional, Boyce, Sara, additional, Bradley, John R., additional, Breen, Gerome, additional, Brennan, Paul, additional, Brewer, Carole, additional, Brown, Matthew, additional, Browning, Andrew C., additional, Browning, Michael J., additional, Buchan, Rachel J., additional, Buckland, Matthew S., additional, Bueser, Teofila, additional, Diz, Carmen Bugarin, additional, Burn, John, additional, Burns, Siobhan O., additional, Burren, Oliver S., additional, Burrows, Nigel, additional, Campbell, Carolyn, additional, Carr-White, Gerald, additional, Carss, Keren, additional, Casey, Ruth, additional, Caulfield, Mark J., additional, Chambers, Jenny, additional, Chambers, John, additional, Chan, Melanie M.Y., additional, Cheng, Floria, additional, Chinnery, Patrick F., additional, Chitre, Manali, additional, Christian, Martin T., additional, Clayton-Smith, Jill, additional, Cleary, Maureen, additional, Brod, Naomi Clements, additional, Colby, Elizabeth, additional, Cole, Trevor R.P., additional, Collins, Janine, additional, Collins, Peter W., additional, Compton, Cecilia J., additional, Cook, H. Terence, additional, Cook, Stuart, additional, Cooper, Nichola, additional, Corris, Paul A., additional, Curry, Nicola S., additional, Daniels, Matthew J., additional, Dattani, Mehul, additional, Daugherty, Louise C., additional, Davis, John, additional, De Soyza, Anthony, additional, Deevi, Sri V.V., additional, Dent, Timothy, additional, Deshpande, Charu, additional, Dewhurst, Eleanor F., additional, Dixon, Peter H., additional, Douzgou, Sofia, additional, Downes, Kate, additional, Drazyk, Anna M., additional, Drewe, Elizabeth, additional, Duarte, Daniel, additional, Dutt, Tina, additional, Edgar, J. David M., additional, Edwards, Karen, additional, Egner, William, additional, Ekani, Melanie N., additional, Elliott, Perry, additional, Erber, Wendy N., additional, Erwood, Marie, additional, Estiu, Maria C., additional, Evans, Dafydd Gareth, additional, Evans, Gillian, additional, Everington, Tamara, additional, Fassihi, Hiva, additional, Favier, Remi, additional, Fletcher, Debra, additional, Flinter, Frances A., additional, Floto, R. Andres, additional, Fowler, Tom, additional, Fox, James, additional, Frary, Amy J., additional, French, Courtney E., additional, Freson, Kathleen, additional, Frontini, Mattia, additional, Furnell, Abigail, additional, Gale, Daniel P., additional, Ganesan, Vijeya, additional, Gattens, Michael, additional, Ghofrani, Hossein-Ardeschir, additional, Gibbs, J. Simon R., additional, Gibson, Kate, additional, Gilmour, Kimberly C., additional, Gleadall, Nicholas S., additional, Goddard, Sarah, additional, Gomez, Keith, additional, Gordins, Pavels, additional, Gosal, David, additional, Graham, Jodie, additional, Grassi, Luigi, additional, Greenhalgh, Lynn, additional, Greinacher, Andreas, additional, Gresele, Paolo, additional, Griffiths, Philip, additional, Grigoriadou, Sofia, additional, Grozeva, Detelina, additional, Gurnell, Mark, additional, Hackett, Scott, additional, Hadinnapola, Charaka, additional, Hague, Rosie, additional, Hague, William M., additional, Haimel, Matthias, additional, Hall, Matthew, additional, Hanson, Helen L., additional, Haque, Eshika, additional, Harkness, Kirsty, additional, Harper, Andrew R., additional, Harris, Claire L., additional, Hart, Daniel, additional, Hassan, Ahamad, additional, Hayman, Grant, additional, Henderson, Alex, additional, Herwadkar, Archana, additional, Hoffman, Jonathan, additional, Horvath, Rita, additional, Houlden, Henry, additional, Houweling, Arjan C., additional, Hu, Fengyuan, additional, Hudson, Gavin, additional, Huissoon, Aarnoud P., additional, Hurles, Matthew, additional, Irving, Melita, additional, Izatt, Louise, additional, James, Roger, additional, Johnson, Sally A., additional, Jolles, Stephen, additional, Jolley, Jennifer, additional, Josifova, Dragana, additional, Jurkute, Neringa, additional, Kasanicki, Mary A., additional, Kazkaz, Hanadi, additional, Kazmi, Rashid, additional, Kelleher, Peter, additional, Kelly, Anne M, additional, Kelsall, Wilf, additional, Kempster, Carly, additional, Kingston, Nathalie, additional, Koelling, Nils, additional, Kostadima, Myrto, additional, Koziell, Ania, additional, Kreuzhuber, Roman, additional, Kuijpers, Taco W., additional, Kumar, Ajith, additional, Kumararatne, Dinakantha, additional, Kurian, Manju A., additional, Laffan, Michael A., additional, Lalloo, Fiona, additional, Lambert, Michele, additional, Allen, Hana Lango, additional, Layton, D. Mark, additional, Lentaigne, Claire, additional, Lester, Tracy, additional, Levine, Adam P., additional, Linger, Rachel, additional, Longhurst, Hilary, additional, Lorenzo, Lorena E., additional, Louka, Eleni, additional, Lyons, Paul A., additional, Madan, Bella, additional, Maher, Eamonn R., additional, Maimaris, Jesmeen, additional, Malka, Samantha, additional, Mangles, Sarah, additional, Mapeta, Rutendo, additional, Marchbank, Kevin J., additional, Marks, Stephen, additional, Markus, Hugh S., additional, Marschall, Hanns-Ulrich, additional, Marshall, Andrew, additional, Mathias, Mary, additional, Matthews, Emma, additional, Maxwell, Heather, additional, McAlinden, Paul, additional, McCarthy, Mark I., additional, McKinney, Harriet, additional, Meacham, Stuart, additional, Mead, Adam J., additional, Mehta, Sarju G., additional, Michaelides, Michel, additional, Millar, Carolyn, additional, Mohammed, Shehla N., additional, Moore, Anthony T., additional, Mozere, Monika, additional, Muir, Keith W., additional, Mumford, Andrew D., additional, Nemeth, Andrea H., additional, Newman, William G., additional, Newnham, Michael, additional, Noorani, Sadia, additional, Nurden, Paquita, additional, O’Sullivan, Jennifer, additional, Obaji, Samya, additional, Odhams, Chris, additional, Okoli, Steven, additional, Olschewski, Andrea, additional, Ong, Kai Ren, additional, Oram, S. Helen, additional, Ormondroyd, Elizabeth, additional, Ouwehand, Willem H., additional, Palles, Claire, additional, Papadia, Sofia, additional, Park, Soo-Mi, additional, Parry, David, additional, Patel, Smita, additional, Paterson, Joan, additional, Peacock, Andrew, additional, Pearce, Simon H., additional, Peerlinck, Kathelijne, additional, Petersen, Romina, additional, Pilkington, Clarissa, additional, Poole, Kenneth E.S., additional, Psaila, Bethan, additional, Pyle, Angela, additional, Quinton, Richard, additional, Rahman, Shamima, additional, Rao, Anupama, additional, Raymond, F. Lucy, additional, Rayner-Matthews, Paula J., additional, Rendon, Augusto, additional, Renton, Tara, additional, Rice, Andrew S.C., additional, Richter, Alex, additional, Robert, Leema, additional, Roberts, Irene, additional, Rose, Sarah J., additional, Ross-Russell, Robert, additional, Roughley, Catherine, additional, Roy, Noemi B.A., additional, Ruddy, Deborah M., additional, Sadeghi-Alavijeh, Omid, additional, Saleem, Moin A., additional, Samani, Nilesh, additional, Samarghitean, Crina, additional, Sanchis-Juan, Alba, additional, Sargur, Ravishankar B., additional, Sarkany, Robert N., additional, Satchell, Simon, additional, Savic, Sinisa, additional, Sayer, Genevieve, additional, Sayer, John A., additional, Scelsi, Laura, additional, Schaefer, Andrew M., additional, Schulman, Sol, additional, Scott, Richard, additional, Scully, Marie, additional, Searle, Claire, additional, Sen, Arjune, additional, Sewell, W.A. Carrock, additional, Seyres, Denis, additional, Shah, Neil, additional, Shamardina, Olga, additional, Shapiro, Susan E., additional, Shaw, Adam C., additional, Sibson, Keith, additional, Side, Lucy, additional, Simeoni, Ilenia, additional, Simpson, Michael A., additional, Sims, Matthew C., additional, Sivapalaratnam, Suthesh, additional, Smedley, Damian, additional, Smith, Katherine R., additional, Smith, Kenneth G.C., additional, Snape, Katie, additional, Soranzo, Nicole, additional, Spasic-Boskovic, Olivera, additional, Staines, Simon, additional, Staples, Emily, additional, Stark, Hannah, additional, Stirrups, Kathleen E., additional, Stuckey, Alex, additional, Syrris, Petros, additional, Tait, R. Campbell, additional, Talks, Kate, additional, Tan, Rhea Y.Y., additional, Taylor, Jenny C., additional, Taylor, John M., additional, Thaventhiran, James E., additional, Themistocleous, Andreas C., additional, Thomas, David, additional, Thomas, Ellen, additional, Thomas, Moira J., additional, Thomas, Patrick, additional, Thomson, Kate, additional, Thrasher, Adrian J., additional, Thys, Chantal, additional, Tischkowitz, Marc, additional, Titterton, Catherine, additional, Toh, Cheng-Hock, additional, Tomlinson, Ian P., additional, Traylor, Matthew, additional, Treadaway, Paul, additional, Tuna, Salih, additional, Turro, Ernest, additional, Twiss, Philip, additional, Vale, Tom, additional, Van Geet, Chris, additional, van Zuydam, Natalie, additional, Vandersteen, Anthony M, additional, Vazquez-Lopez, Marta, additional, von Ziegenweidt, Julie, additional, Wagner, Annette, additional, Waisfisz, Quinten, additional, Walker, Neil, additional, Walker, Suellen M., additional, Ware, James S., additional, Watkins, Hugh, additional, Watt, Christopher, additional, Webster, Andrew R., additional, Wedderburn, Lucy, additional, Wei, Wei, additional, Welch, Steven B., additional, Wessels, Julie, additional, Westbury, Sarah K., additional, Westwood, John-Paul, additional, Whitehorn, Deborah, additional, Whitworth, James, additional, Wilkie, Andrew O.M., additional, Williamson, Catherine, additional, Wilson, Brian T., additional, Wong, Edwin K.S., additional, Wood, Nicholas, additional, Wood, Yvette, additional, Woods, Christopher Geoffrey, additional, Woodward, Emma R., additional, Worth, Austen, additional, Wright, Michael, additional, Yates, Katherine, additional, Yong, Patrick F.K., additional, Young, Timothy, additional, Yu, Ping, additional, Yu-Wai-Man, Patrick, additional, Zlamalova, Eliska, additional, Hirsch, Russel, additional, White, R. James, additional, Simon, Marc, additional, Badesch, David, additional, Rosenzweig, Erika, additional, Burger, Charles, additional, Chakinala, Murali, additional, Thenappan, Thenappan, additional, Elliott, Greg, additional, Simms, Robert, additional, Farber, Harrison, additional, Frantz, Robert, additional, Elwing, Jean, additional, Hill, Nicholas, additional, Ivy, Dunbar, additional, Klinger, James, additional, Nathan, Steven, additional, Oudiz, Ronald, additional, Robbins, Ivan, additional, Schilz, Robert, additional, Fortin, Terry, additional, Wilt, Jeffrey, additional, Yung, Delphine, additional, Austin, Eric, additional, Ahmad, Ferhaan, additional, Bhatt, Nitin, additional, Lahm, Tim, additional, Frost, Adaani, additional, Safdar, Zeenat, additional, Rehman, Zia, additional, Walter, Robert, additional, Torres, Fernando, additional, Bakshi, Sahil, additional, Archer, Stephen, additional, Argula, Rahul, additional, Barnett, Christopher, additional, Benza, Raymond, additional, Desai, Ankit, additional, and Maddipati, Veeranna, additional
Published: 2021
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15. SMIM1absence is associated with reduced energy expenditure and excess weight

Author: Stefanucci, Luca, Moslemi, Camous, Tomé, Ana R., Virtue, Samuel, Bidault, Guillaume, Gleadall, Nicholas S., Watson, Laura P.E., Kwa, Jing E., Burden, Frances, Farrow, Samantha, Banasik, Karina, Bay, Jakob, Boldsen, Jens Kjærgaard, Brodersen, Thorsten, Brunak, Søren, Burgdorf, Kristoffer, Chalmer, Mona Ameri, Didriksen, Maria, Dinh, Khoa Manh, Dowsett, Joseph, Erikstrup, Christian, Feenstra, Bjarke, Geller, Frank, Gudbjartsson, Daniel, Hansen, Thomas Folkmann, Hindhede, Lotte, Hjalgrim, Henrik, Jacobsen, Rikke Louise, Jemec, Gregor, Jensen, Bitten Aagaard, Kaspersen, Katrine, Kjerulff, Bertram Dalskov, Kogelman, Lisette, Hørup Larsen, Margit Anita, Louloudis, Ioannis, Lundgaard, Agnete, Susan, Mikkelsen, Christina, Nissen, Ioanna, Nyegaard, Mette, Ostrowski, Sisse Rye, Pedersen, Ole Birger, Henriksen, Alexander Pil, Rohde, Palle Duun, Rostgaard, Klaus, Schwinn, Michael, Stefansson, Kari, Stefánsson, Hreinn, Sørensen, Erik, þorsteinsdóttir, Unnur, Thørner, Lise Wegner, Bruun, Mie Topholm, Ullum, Henrik, Werge, Thomas, Westergaard, David, Chen, Ji, Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian’an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Katie Chan, Kei Hang, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Loz, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V.R., Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P., Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Southam, Lorraine, Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J.L., Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J.C., Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M. Arfan, Johnson, W. Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R.H.J., Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, Van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Goncalo R., Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Ida Chen, Yii-Der, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, Janaka de Silva, H., Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J. Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L.R., Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J.F., Magnusson, Patrik K.E., Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P. Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I.A., Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E. Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G.M., Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C.J., Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., Barroso, Inês, Võsa, Urmo, Burling, Keith, Walker, Lindsay, Ord, John, Barker, Peter, Warner, James, Frary, Amy, Renhstrom, Karola, Ashford, Sofie E., Piper, Jo, Biggs, Gail, Erber, Wendy N., Hoffman, Gary J., Schoenmakers, Nadia, Erikstrup, Christian, Rieneck, Klaus, Dziegiel, Morten H., Ullum, Henrik, Azzu, Vian, Vacca, Michele, Aparicio, Hugo Javier, Hui, Qin, Cho, Kelly, Sun, Yan V., Wilson, Peter W., Bayraktar, Omer A., Vidal-Puig, Antonio, Ostrowski, Sisse R., Astle, William J., Olsson, Martin L., Storry, Jill R., Pedersen, Ole B., Ouwehand, Willem H., Chatterjee, Krishna, Vuckovic, Dragana, and Frontini, Mattia
Abstract: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.
Published: 2024
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16. Publisher Correction:Whole-genome sequencing of a sporadic primary immunodeficiency cohort (Nature, (2020), 583, 7814, (90-95), 10.1038/s41586-020-2265-1)

Author: Thaventhiran, James E.D., Lango Allen, Hana, Burren, Oliver S., Rae, William, Greene, Daniel, Staples, Emily, Zhang, Zinan, Farmery, James H.R., Simeoni, Ilenia, Rivers, Elizabeth, Maimaris, Jesmeen, Penkett, Christopher J., Stephens, Jonathan, Deevi, Sri V.V., Sanchis-Juan, Alba, Gleadall, Nicholas S., Thomas, Moira J., Sargur, Ravishankar B., Gordins, Pavels, Baxendale, Helen E., Brown, Matthew, Tuijnenburg, Paul, Worth, Austen, Hanson, Steven, Linger, Rachel J., Buckland, Matthew S., Rayner-Matthews, Paula J., Gilmour, Kimberly C., Samarghitean, Crina, Seneviratne, Suranjith L., Sansom, David M., Lynch, Andy G., Megy, Karyn, Ellinghaus, Eva, Ellinghaus, David, Jorgensen, Silje F., Karlsen, Tom H., Stirrups, Kathleen E., Cutler, Antony J., Kumararatne, Dinakantha S., Chandra, Anita, Edgar, J. David M., Herwadkar, Archana, Cooper, Nichola, Grigoriadou, Sofia, Huissoon, Aarnoud P., Goddard, Sarah, Jolles, Stephen, Schuetz, Catharina, Boschann, Felix, Abbs, Stephen, Adhya, Zoe, Adlard, Julian, Afzal, Maryam, Ahmed, Irshad, Ahmed, Munaza, Ahmed, Saeed, Aitman, Timothy J., Alachkar, Hana, Alamelu, Jayanthi, Alikhan, Raza, Allen, Carl E., Allen, Louise, Allsup, David J., Alvi, Arif, Ambegaonkar, Gautam, Anantharachagan, Ariharan, Ancliff, Philip, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Arumugakani, Gururaj, Arya, Rita, Ashford, Sofie, Astle, William J., Attwood, Anthony, Austin, Steve, Aydinok, Yesim, Ayub, Waqar, Babbs, Christian, Bacchelli, Chiara, Baglin, Trevor, Bakchoul, Tamam, Bariana, Tadbir K., Barratt, Jonathan, Barwell, Julian, Baski, John, Bates, Rachel W., Batista, Joana, Baynam, Gareth, Bennett, David L., Bethune, Claire, Bhatnagar, Neha, Bibi, Shahnaz, Bierzynska, Agnieszka, Biss, Tina, Bitner-Glindzicz, Maria A.K., Bleda, Marta, Blesneac, Iulia, Boardman, Barbara, Boddana, Preetham, Bogaard, Harm J., Booth, Claire, Boyce, Sara, Bradley, John R., Brady, Angela, Breen, Gerome, Brennan, Paul, Brewer, Carole, Briley, Annette, Brown, Richard, Browning, Michael J., Brownlie, Mary, Bryson, Christine J., Buchan, Rachel J., Buck, Jackie, Bueser, Teofila, Diz, Carmen Bugarin, Burns, Siobhan O., Calleja, Paul, Carmichael, Jenny, Carr-White, Gerald, Carss, Keren J., Casey, Ruth, Chalmers, Elizabeth, Chambers, Jenny, Chambers, John, Chan, Melanie M.Y., Chan, Melissa V., Cheng, Floria, Chinn, Ivan K., Chinnery, Patrick F., Chitre, Manali, Chong, Sam, Christian, Martin T., Church, Colin, Clement, Emma M., Brod, Naomi Clements, Clifford, Hayley, Clowes, Virginia E., Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor R.P., Collins, Janine H., Collins, Peter W., Condliffe, Robin, Cook, H. Terence, Cook, Stuart, Cookson, Victoria, Corris, Paul A., Creaser-Myers, Amanda, Crisp-Hihn, Abigail, Curry, Nicola S., Da Costa, Rosa, Danesino, Cesare, Daniels, Matthew J., Darby, Damaris, Daugherty, Louise C., Davies, E. G., Davies, Sophie, Davis, John, de Bree, Godelieve J., Deacock, Sarah, Deegan, Patrick B., Dempster, John, Dent, Timothy, Deshpande, Charu, Devlin, Lisa A., Dewhurst, Eleanor F., Dixit, Anand K., Dixon, Peter H., Doffinger, Rainer, Dolling, Helen, Dormand, Natalie, Downes, Kate, Drazyk, Anna M., Drewe, Elizabeth, Duarte, Daniel, Dutt, Tina, Edwards, Karen E., Egner, William, Ekani, Melanie N., El-Shanawany, Tariq, Elkhalifa, Shuayb, Elston, Tony, Emmerson, Ingrid, Erber, Wendy N., Erwood, Marie, Estiu, Maria C., Evans, Dafydd Gareth, Evans, Gillian, Everington, Tamara, Eyries, Mélanie, Favier, Remi, Firth, Helen V., Fitzpatrick, Maggie M., Fletcher, Debra, Flinter, Frances A., Fox, James C., Frary, Amy J., French, Courtney E., Freson, Kathleen, Frontini, Mattia, Furie, Bruce, Gale, Daniel P., Gall, Henning J., Gardham, Alice, Gaspar, H. Bobby, Gattens, Michael, Ghali, Neeti, Ghataorhe, Pavandeep K., Ghio, Stefano, Ghofrani, Hossein Ardeschir, Ghurye, Rohit, Gibbs, J. Simon R., Gilbert, Rodney D., Girerd, Barbara, Girling, Joanna C., Gissen, Paul, Gorman, Kathleen M., Gosal, David, Graf, Stefan, Grassi, Luigi, Greenhalgh, Alan J., Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip G., Griffiths, Sian, Grozeva, Detelina, Hackett, Scott J., Hadden, Robert D.M., Hadinnapola, Charaka, Hague, Rosie, Hague, William M., Haimel, Matthias, Hall, Matthew, Halmagyi, Csaba, Hammerton, Tracey, Hanson, Helen L., Harkness, Kirsty, Harper, Andrew R., Harper, Lorraine, Harris, Claire, Harrison, Claire, Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Heemskerk, Johan W.M., Hegde, Shivaram, Henderson, Alex, Henderson, Robert H., Hensiek, Anke, Henskens, Yvonne M.C., Hodgson, Joshua, Hoffman, Jonathan, Holden, Simon, Holder, Muriel, Horvath, Rita, Houlden, Henry, Houweling, Arjan C., Howard, Luke S., Hu, Fengyuan, Hudson, Gavin, Hughes, Sean, Hughes, Stephen, Huis in ‘t Veld, Anna E., Humbert, Marc, Hurles, Matthew E., Hurst, Jane A., Irvine, Val, Izatt, Louise, James, Roger, Jeevaratnam, Praveen, Johnson, Mark, Johnson, Sally A., Jolley, Jennifer D., Jones, Bryony, Jones, Julie, Josifova, Dragana, Jurkute, Neringa, Karim, Yousuf M., Karoshi, Mahantesh A., Kasanicki, Mary A., Kazkaz, Hanadi, Kazmi, Rashid, Keeling, David, Kelleher, Peter, Kelly, Anne M., Kempster, Carly, Kennedy, Fiona, Kiani, Sorena, Kiely, David G., Kingston, Nathalie, Kinsey, Sally, Klein, Nigel, Klima, Robert, Knox, Ellen, Kostadima, Myrto A., Kovacs, Gabor, Koziell, Ania B., Kreuzhuber, Roman, Krishnakumar, Deepa, Kuijpers, Taco W., Kumar, Ajith, Kurian, Manju A., Laffan, James, Laffan, Michael A., Lalloo, Fiona, Lambert, Michele P., Lawman, Sarah H.A., Lawrie, Allan, Layton, D. Mark, Lear, Sara E., Lees, Melissa M., Lentaigne, Claire, Levine, Adam P., Lewington, Andrew J.P., Li, Wei, Liesner, Ri, Liu, Bin, Longhurst, Hilary, Lorenzo, Lorena E., Louka, Eleni, Hadeler, Silvia Lucato, Lyons, Paul A., Macdougall, Malcolm, Machado, Rajiv D., MacKenzie Ross, Robert V., Mackillop, Lucy H., MacLaren, Robert, Madan, Bella, Magee, Laura, Mahdi-Rogers, Mohamed, Maher, Eamonn R., Makris, Mike, Mangles, Sarah, Manson, Ania, Manzur, Adnan, Mapeta, Rutendo, Marchbank, Kevin J., Mark, Patrick B., Marks, Stephen, Markus, Hugh S., Marschall, Hanns Ulrich, Marshall, Andrew, Martin, Jennifer M., Masati, Larahmie, Mathias, Mary, Matser, Vera, Matthews, Emma L., Maw, Anna, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark I., McDermott, Elizabeth M., McGowan, Simon J., McJannet, Coleen, McKinney, Harriet, Meacham, Stuart, Mead, Adam J., Castello, Ignacio Medina, Meehan, Sharon, Mehta, Sarju, Mercer, Catherine L., Michaelides, Michel, Michell, Anna C., Milford, David, Millar, Carolyn M., Millar, Hazel, Mistry, Anoop, Moenen, Floor, Moledina, Shahin, Montani, David, Moore, Anthony T., Moore, Jason, Morrell, Nicholas W., Morrisson, Valerie, Mozere, Monika, Muir, Keith W., Mumford, Andrew D., Murng, Sai H.K., Nasir, Iman, Nejentsev, Sergey, Newnham, Michael, Ng, Joanne, Ngoh, Adeline, Noorani, Sadia, Noori, Muna, Nurden, Paquita, O’Sullivan, Jennifer M., Obaji, Samya, Okoli, Steven, Oksenhendler, Eric, Olschewski, Andrea, Olschewski, Horst, Ong, Albert C.M., Ong, Kai Ren, Oram, Helen, Ormondroyd, Elizabeth, Othman, Shokri, Ouwehand, Willem H., Pantazis, Antonis, Papadia, Sofia, Papandreou, Apostolos, Park, Soo Mi, Parker, Alasdair P.J., Parry, David, Parsons, Georgina, Pasi, K. John, Paterson, Joan, Payne, Jeanette H., Peacock, Andrew J., Peerlinck, Kathelijne, Pepke-Zaba, Joanna, Perry, David, Petersen, Romina, Piechowski-Jozwiak, Bartlomiej, Pinto, Fernando, Polwarth, Gary J., Ponsford, Mark J., Prasad, Sanjay, Prokopenko, Inga, Psaila, Beth, Pyle, Angela, Qasim, Waseem, Quinn, Ellen, Quinti, Isabella, Raina, Sanjay, Ranganathan, Lavanya, Rankin, Julia, Rankin, Stuart, Rao, Anupama, Raymond, F. Lucy, Rehnstrom, Karola, Reid, Evan, Reilly, Mary M., Renton, Tara, Revel-Vilk, Shoshana, Rhodes, Christopher J., Rice, Andrew S.C., Richards, Emma E., Richards, Mike, Richardson, Sylvia, Richter, Alex, Robert, Leema, Roberts, Irene, Rondina, Matthew T., Rosser, Elisabeth, Rothwell, Peter, Roughley, Catherine, Roy, Noemi B., Rue-Albrecht, Kevin, Sadeghi-Alavijeh, Omid, Saleem, Moin A., Salmon, Richard M., Samani, Nilesh J., Sambrook, Jennifer G., Sandford, Richard, Santra, Saikat, Satchell, Simon C., Savic, Sinisa, Scelsi, Laura, Schotte, Gwen, Schulman, Sol, Schulze, Harald, Scott, Richard, Scully, Marie, Searle, Claire, Seeger, Werner, Sewell, W. A.Carrock, Seyres, Denis, Shackley, Fiona, Shamardina, Olga, Shapiro, Susan E., Sharma, Pankaj, Shehata, Hassan A., Shipley, Deborah, Shtoyerman, Rakefet, Sibson, Keith, Side, Lucy, Simpson, Michael, Sims, Matthew C., Sinha, Manish D., Sivapalaratnam, Suthesh, Skytte, Anne Bine, Smith, Kenneth G.C., Snape, Katie, Sneddon, Linda, Sohal, Aman, Soubrier, Florent, Southgate, Laura, Southwood, Mark, Splitt, Miranda, Staines, Simon, Stark, Hannah, Stauss, Hans, Steele, Cathal L., Stein, Daniel, Stein, Penelope E., Stock, Sophie, Stubbs, Matthew J., Suntharalingam, Jay, Swietlik, Emilia M., Symington, Emily, Tait, R. Campbell, Talks, Kate, Tan, Rhea Y.Y., Taylor, Gordon B., Thachil, Jecko, Themistocleous, Andreas C., Thomas, David C., Thomas, Ellen, Thomas, Patrick, Thompson, Dorothy A., Thomson, Kate, Thrasher, Adrian J., Thys, Chantal, Tilly, Tobias, Tischkowitz, Marc, Titterton, Catherine, Todd, John A., Toh, Cheng Hock, Tool, Anton T.J., Toshner, Mark R., Traylor, Matthew, Treacy, Carmen M., Treadaway, Paul, Trembath, Richard C., Trippier, Sarah, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Upton, Paul D., Urniaz, Rafal, Vale, Tom, Van Geet, Chris, van Zuydam, Natalie, Vandersteen, Anthony M., Vazquez-Lopez, Marta, Veltman, Marijcke W.M., Vogt, Julie, von Ziegenweidt, Julie, Noordegraaf, Anton Vonk, Vora, Ajay, Vries, Minka J.A., Wakeling, Emma L., Walker, Neil, Walker, Suellen M., Walsh, Roddy, Wanjiku, Ivy, Ware, James S., Warner, Timothy Q., Wassmer, Evangeline, Watkins, Hugh, Watson, Henry G., Watt, Christopher, Waugh, Dean, Webb, Nick, Webster, Andrew R., Wei, Wei, Welch, Angela, Welch, Steven B., Werring, David, Wessels, Julie, Westbury, Sarah K., Westwood, John Paul W., Wharton, John, Whitehorn, Deborah, Whitworth, James, Wilkins, Martin R., Willcocks, Lisa, Williams, David J., Williamson, Catherine, Wong, Edwin K.S., Wood, Nicholas, Wood, Yvette, Woods, Christopher Geoffrey, Woodward, Emma R., Workman, Sarita, Wort, Stephen J., Yates, Katherine, Yeatman, Nigel, Yong, Patrick F.K., Young, Timothy, Yu, Ping, Yu-Wai-Man, Patrick, Zlamalova, Eliska, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2020

17. Whole-genome sequencing of patients with rare diseases in a national health system

Author: Turro, Ernest, Astle, William J., Megy, Karyn, Gräf, Stefan, Greene, Daniel, Shamardina, Olga, Allen, Hana Lango, Sanchis-Juan, Alba, Frontini, Mattia, Thys, Chantal, Stephens, Jonathan, Mapeta, Rutendo, Burren, Oliver S., Downes, Kate, Haimel, Matthias, Tuna, Salih, Deevi, Sri V. V., Aitman, Timothy J., Bennett, David L., Calleja, Paul, Carss, Keren, Caulfield, Mark J., Chinnery, Patrick F., Dixon, Peter H., Gale, Daniel P., James, Roger, Koziell, Ania, Laffan, Michael A., Levine, Adam P., Maher, Eamonn R., Markus, Hugh S., Morales, Joannella, Morrell, Nicholas W., Mumford, Andrew D., Ormondroyd, Elizabeth, Rankin, Stuart, Rendon, Augusto, Richardson, Sylvia, Roberts, Irene, Roy, Noemi B. A., Saleem, Moin A., Smith, Kenneth G. C., Stark, Hannah, Tan, Rhea Y. Y., Themistocleous, Andreas C., Thrasher, Adrian J., Watkins, Hugh, Webster, Andrew R., Wilkins, Martin R., Williamson, Catherine, Whitworth, James, Humphray, Sean, Bentley, David R., Kingston, Nathalie, Walker, Neil, Bradley, John R., Ashford, Sofie, Penkett, Christopher J., Freson, Kathleen, Stirrups, Kathleen E., Raymond, F. Lucy, Ouwehand, Willem H., Peacock, Andrew, Hague, Rosie, Maxwell, Heather, Muir, Keith W., Tait, R. Campbell, and Thomas, Moira J.
Abstract: Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
Published: 2020

18. Whole-genome sequencing of a sporadic primary immunodeficiency cohort

Author: Thaventhiran, James E.D., Lango Allen, Hana, Burren, Oliver S., Rae, William, Greene, Daniel, Staples, Emily, Zhang, Zinan, Farmery, James H.R., Simeoni, Ilenia, Rivers, Elizabeth, Maimaris, Jesmeen, Penkett, Christopher J., Stephens, Jonathan, Deevi, Sri V.V., Sanchis-Juan, Alba, Gleadall, Nicholas S., Thomas, Moira J., Sargur, Ravishankar B., Gordins, Pavels, Baxendale, Helen E., Brown, Matthew, Tuijnenburg, Paul, Worth, Austen, Hanson, Steven, Linger, Rachel J., Buckland, Matthew S., Rayner-Matthews, Paula J., Gilmour, Kimberly C., Samarghitean, Crina, Seneviratne, Suranjith L., Sansom, David M., Lynch, Andy G., Megy, Karyn, Ellinghaus, Eva, Ellinghaus, David, Jorgensen, Silje F., Karlsen, Tom H., Stirrups, Kathleen E., Cutler, Antony J., Kumararatne, Dinakantha S., Chandra, Anita, Edgar, J. David M., Herwadkar, Archana, Cooper, Nichola, Grigoriadou, Sofia, Huissoon, Aarnoud P., Goddard, Sarah, Jolles, Stephen, Schuetz, Catharina, Boschann, Felix, Abbs, Stephen, Adhya, Zoe, Adlard, Julian, Afzal, Maryam, Ahmed, Irshad, Ahmed, Munaza, Ahmed, Saeed, Aitman, Timothy J., Alachkar, Hana, Alamelu, Jayanthi, Alikhan, Raza, Allen, Carl E., Allen, Louise, Allsup, David J., Alvi, Arif, Ambegaonkar, Gautam, Anantharachagan, Ariharan, Ancliff, Philip, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Arumugakani, Gururaj, Arya, Rita, Ashford, Sofie, Astle, William J., Attwood, Anthony, Austin, Steve, Aydinok, Yesim, Ayub, Waqar, Babbs, Christian, Bacchelli, Chiara, Baglin, Trevor, Bakchoul, Tamam, Bariana, Tadbir K., Barratt, Jonathan, Barwell, Julian, Baski, John, Bates, Rachel W., Batista, Joana, Baynam, Gareth, Bennett, David L., Bethune, Claire, Bhatnagar, Neha, Bibi, Shahnaz, Bierzynska, Agnieszka, Biss, Tina, Bitner-Glindzicz, Maria A.K., Bleda, Marta, Blesneac, Iulia, Boardman, Barbara, Boddana, Preetham, Bogaard, Harm J., Booth, Claire, Boyce, Sara, Bradley, John R., Brady, Angela, Breen, Gerome, Brennan, Paul, Brewer, Carole, Briley, Annette, Brown, Richard, Browning, Michael J., Brownlie, Mary, Bryson, Christine J., Buchan, Rachel J., Buck, Jackie, Bueser, Teofila, Diz, Carmen Bugarin, Burns, Siobhan O., Calleja, Paul, Carmichael, Jenny, Carr-White, Gerald, Carss, Keren J., Casey, Ruth, Chalmers, Elizabeth, Chambers, Jenny, Chambers, John, Chan, Melanie M.Y., Chan, Melissa V., Cheng, Floria, Chinn, Ivan K., Chinnery, Patrick F., Chitre, Manali, Chong, Sam, Christian, Martin T., Church, Colin, Clement, Emma M., Brod, Naomi Clements, Clifford, Hayley, Clowes, Virginia E., Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor R.P., Collins, Janine H., Collins, Peter W., Condliffe, Robin, Cook, H. Terence, Cook, Stuart, Cookson, Victoria, Corris, Paul A., Creaser-Myers, Amanda, Crisp-Hihn, Abigail, Curry, Nicola S., Da Costa, Rosa, Danesino, Cesare, Daniels, Matthew J., Darby, Damaris, Daugherty, Louise C., Davies, E. G., Davies, Sophie, Davis, John, de Bree, Godelieve J., Deacock, Sarah, Deegan, Patrick B., Dempster, John, Dent, Timothy, Deshpande, Charu, Devlin, Lisa A., Dewhurst, Eleanor F., Dixit, Anand K., Dixon, Peter H., Doffinger, Rainer, Dolling, Helen, Dormand, Natalie, Downes, Kate, Drazyk, Anna M., Drewe, Elizabeth, Duarte, Daniel, Dutt, Tina, Edwards, Karen E., Egner, William, Ekani, Melanie N., El-Shanawany, Tariq, Elkhalifa, Shuayb, Elston, Tony, Emmerson, Ingrid, Erber, Wendy N., Erwood, Marie, Estiu, Maria C., Evans, Dafydd Gareth, Evans, Gillian, Everington, Tamara, Eyries, Mélanie, Favier, Remi, Firth, Helen V., Fitzpatrick, Maggie M., Fletcher, Debra, Flinter, Frances A., Fox, James C., Frary, Amy J., French, Courtney E., Freson, Kathleen, Frontini, Mattia, Furie, Bruce, Gale, Daniel P., Gall, Henning J., Gardham, Alice, Gaspar, H. Bobby, Gattens, Michael, Ghali, Neeti, Ghataorhe, Pavandeep K., Ghio, Stefano, Ghofrani, Hossein Ardeschir, Ghurye, Rohit, Gibbs, J. Simon R., Gilbert, Rodney D., Girerd, Barbara, Girling, Joanna C., Gissen, Paul, Gorman, Kathleen M., Gosal, David, Graf, Stefan, Grassi, Luigi, Greenhalgh, Alan J., Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip G., Griffiths, Sian, Grozeva, Detelina, Hackett, Scott J., Hadden, Robert D.M., Hadinnapola, Charaka, Hague, Rosie, Hague, William M., Haimel, Matthias, Hall, Matthew, Halmagyi, Csaba, Hammerton, Tracey, Hanson, Helen L., Harkness, Kirsty, Harper, Andrew R., Harper, Lorraine, Harris, Claire, Harrison, Claire, Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Heemskerk, Johan W.M., Hegde, Shivaram, Henderson, Alex, Henderson, Robert H., Hensiek, Anke, Henskens, Yvonne M.C., Hodgson, Joshua, Hoffman, Jonathan, Holden, Simon, Holder, Muriel, Horvath, Rita, Houlden, Henry, Houweling, Arjan C., Howard, Luke S., Hu, Fengyuan, Hudson, Gavin, Hughes, Sean, Hughes, Stephen, Huis in ‘t Veld, Anna E., Humbert, Marc, Hurles, Matthew E., Hurst, Jane A., Irvine, Val, Izatt, Louise, James, Roger, Jeevaratnam, Praveen, Johnson, Mark, Johnson, Sally A., Jolley, Jennifer D., Jones, Bryony, Jones, Julie, Josifova, Dragana, Jurkute, Neringa, Karim, Yousuf M., Karoshi, Mahantesh A., Kasanicki, Mary A., Kazkaz, Hanadi, Kazmi, Rashid, Keeling, David, Kelleher, Peter, Kelly, Anne M., Kempster, Carly, Kennedy, Fiona, Kiani, Sorena, Kiely, David G., Kingston, Nathalie, Kinsey, Sally, Klein, Nigel, Klima, Robert, Knox, Ellen, Kostadima, Myrto A., Kovacs, Gabor, Koziell, Ania B., Kreuzhuber, Roman, Krishnakumar, Deepa, Kuijpers, Taco W., Kumar, Ajith, Kurian, Manju A., Laffan, James, Laffan, Michael A., Lalloo, Fiona, Lambert, Michele P., Lawman, Sarah H.A., Lawrie, Allan, Layton, D. Mark, Lear, Sara E., Lees, Melissa M., Lentaigne, Claire, Levine, Adam P., Lewington, Andrew J.P., Li, Wei, Liesner, Ri, Liu, Bin, Longhurst, Hilary, Lorenzo, Lorena E., Louka, Eleni, Hadeler, Silvia Lucato, Lyons, Paul A., Macdougall, Malcolm, Machado, Rajiv D., MacKenzie Ross, Robert V., Mackillop, Lucy H., MacLaren, Robert, Madan, Bella, Magee, Laura, Mahdi-Rogers, Mohamed, Maher, Eamonn R., Makris, Mike, Mangles, Sarah, Manson, Ania, Manzur, Adnan, Mapeta, Rutendo, Marchbank, Kevin J., Mark, Patrick B., Marks, Stephen, Markus, Hugh S., Marschall, Hanns Ulrich, Marshall, Andrew, Martin, Jennifer M., Masati, Larahmie, Mathias, Mary, Matser, Vera, Matthews, Emma L., Maw, Anna, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark I., McDermott, Elizabeth M., McGowan, Simon J., McJannet, Coleen, McKinney, Harriet, Meacham, Stuart, Mead, Adam J., Castello, Ignacio Medina, Meehan, Sharon, Mehta, Sarju, Mercer, Catherine L., Michaelides, Michel, Michell, Anna C., Milford, David, Millar, Carolyn M., Millar, Hazel, Mistry, Anoop, Moenen, Floor, Moledina, Shahin, Montani, David, Moore, Anthony T., Moore, Jason, Morrell, Nicholas W., Morrisson, Valerie, Mozere, Monika, Muir, Keith W., Mumford, Andrew D., Murng, Sai H.K., Nasir, Iman, Nejentsev, Sergey, Newnham, Michael, Ng, Joanne, Ngoh, Adeline, Noorani, Sadia, Noori, Muna, Nurden, Paquita, O’Sullivan, Jennifer M., Obaji, Samya, Okoli, Steven, Oksenhendler, Eric, Olschewski, Andrea, Olschewski, Horst, Ong, Albert C.M., Ong, Kai Ren, Oram, Helen, Ormondroyd, Elizabeth, Othman, Shokri, Ouwehand, Willem H., Pantazis, Antonis, Papadia, Sofia, Papandreou, Apostolos, Park, Soo Mi, Parker, Alasdair P.J., Parry, David, Parsons, Georgina, Pasi, K. John, Paterson, Joan, Payne, Jeanette H., Peacock, Andrew J., Peerlinck, Kathelijne, Pepke-Zaba, Joanna, Perry, David, Petersen, Romina, Piechowski-Jozwiak, Bartlomiej, Pinto, Fernando, Polwarth, Gary J., Ponsford, Mark J., Prasad, Sanjay, Prokopenko, Inga, Psaila, Beth, Pyle, Angela, Qasim, Waseem, Quinn, Ellen, Quinti, Isabella, Raina, Sanjay, Ranganathan, Lavanya, Rankin, Julia, Rankin, Stuart, Rao, Anupama, Raymond, F. Lucy, Rehnstrom, Karola, Reid, Evan, Reilly, Mary M., Renton, Tara, Revel-Vilk, Shoshana, Rhodes, Christopher J., Rice, Andrew S.C., Richards, Emma E., Richards, Mike, Richardson, Sylvia, Richter, Alex, Robert, Leema, Roberts, Irene, Rondina, Matthew T., Rosser, Elisabeth, Rothwell, Peter, Roughley, Catherine, Roy, Noemi B., Rue-Albrecht, Kevin, Sadeghi-Alavijeh, Omid, Saleem, Moin A., Salmon, Richard M., Samani, Nilesh J., Sambrook, Jennifer G., Sandford, Richard, Santra, Saikat, Satchell, Simon C., Savic, Sinisa, Scelsi, Laura, Schotte, Gwen, Schulman, Sol, Schulze, Harald, Scott, Richard, Scully, Marie, Searle, Claire, Seeger, Werner, Sewell, W. A.Carrock, Seyres, Denis, Shackley, Fiona, Shamardina, Olga, Shapiro, Susan E., Sharma, Pankaj, Shehata, Hassan A., Shipley, Deborah, Shtoyerman, Rakefet, Sibson, Keith, Side, Lucy, Simpson, Michael, Sims, Matthew C., Sinha, Manish D., Sivapalaratnam, Suthesh, Skytte, Anne Bine, Smith, Kenneth G.C., Snape, Katie, Sneddon, Linda, Sohal, Aman, Soubrier, Florent, Southgate, Laura, Southwood, Mark, Splitt, Miranda, Staines, Simon, Stark, Hannah, Stauss, Hans, Steele, Cathal L., Stein, Daniel, Stein, Penelope E., Stock, Sophie, Stubbs, Matthew J., Suntharalingam, Jay, Swietlik, Emilia M., Symington, Emily, Tait, R. Campbell, Talks, Kate, Tan, Rhea Y.Y., Taylor, Gordon B., Thachil, Jecko, Themistocleous, Andreas C., Thomas, David C., Thomas, Ellen, Thomas, Patrick, Thompson, Dorothy A., Thomson, Kate, Thrasher, Adrian J., Thys, Chantal, Tilly, Tobias, Tischkowitz, Marc, Titterton, Catherine, Todd, John A., Toh, Cheng Hock, Tool, Anton T.J., Toshner, Mark R., Traylor, Matthew, Treacy, Carmen M., Treadaway, Paul, Trembath, Richard C., Trippier, Sarah, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Upton, Paul D., Urniaz, Rafal, Vale, Tom, Van Geet, Chris, van Zuydam, Natalie, Vandersteen, Anthony M., Vazquez-Lopez, Marta, Veltman, Marijcke W.M., Vogt, Julie, von Ziegenweidt, Julie, Noordegraaf, Anton Vonk, Vora, Ajay, Vries, Minka J.A., Wakeling, Emma L., Walker, Neil, Walker, Suellen M., Walsh, Roddy, Wanjiku, Ivy, Ware, James S., Warner, Timothy Q., Wassmer, Evangeline, Watkins, Hugh, Watson, Henry G., Watt, Christopher, Waugh, Dean, Webb, Nick, Webster, Andrew R., Wei, Wei, Welch, Angela, Welch, Steven B., Werring, David, Wessels, Julie, Westbury, Sarah K., Westwood, John Paul W., Wharton, John, Whitehorn, Deborah, Whitworth, James, Wilkins, Martin R., Willcocks, Lisa, Williams, David J., Williamson, Catherine, Wong, Edwin K.S., Wood, Nicholas, Wood, Yvette, Woods, Christopher Geoffrey, Woodward, Emma R., Workman, Sarita, Wort, Stephen J., Yates, Katherine, Yeatman, Nigel, Yong, Patrick F.K., Young, Timothy, Yu, Ping, Yu-Wai-Man, Patrick, Zlamalova, Eliska, Wellcome Trust, Thaventhiran, James [0000-0001-8616-074X], Lango Allen, Hana [0000-0002-7803-8688], Burren, Oliver [0000-0002-3388-5760], Rae, William [0000-0003-0095-2514], Zhang, Zinan [0000-0003-3831-2272], Megy, Karyn [0000-0002-2826-3879], Johnson, Kathleen [0000-0002-6823-3252], Smith, Kenneth [0000-0003-3829-4326], Apollo - University of Cambridge Repository, University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, Ege Üniversitesi, Experimental Immunology, Graduate School, AII - Inflammatory diseases, Infectious diseases, APH - Aging & Later Life, APH - Global Health, Paediatric Infectious Diseases / Rheumatology / Immunology, ARD - Amsterdam Reproduction and Development, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Human genetics, APH - Quality of Care, ACS - Atherosclerosis & ischemic syndromes, Biochemie, RS: Carim - B03 Cell biochemistry of thrombosis and haemostasis, Faculteit FHML Centraal, MUMC+: DA CDL Algemeen (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Hematologie (9), Interne Geneeskunde, and Promovendi CD
Subjects: 0301 basic medicine, Male, Protein Tyrosine Phosphatase, Non-Receptor Type 2/genetics, Genome-wide association study, VARIANTS, Regulatory Sequences, Nucleic Acid, medicine.disease_cause, Genome, Cohort Studies, 0302 clinical medicine, RARE, QR180 Immunology, Primary Immunodeficiency Consortium for the NIHR Bioresource, Genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 2, Multidisciplinary, Suppressor of Cytokine Signaling 1 Protein/genetics, GENETIC-VARIATION, RNA-Binding Proteins, Primary Immunodeficiency Diseases/diagnosis, ASSOCIATION, Penetrance, Multidisciplinary Sciences, DEFICIENCY, QR180, Science & Technology - Other Topics, Female, General Science & Technology, Primary Immunodeficiency Diseases, Transcription Factors/genetics, Genomics, COMMON VARIABLE IMMUNODEFICIENCY, QH426 Genetics, Biology, Article, Actin-Related Protein 2-3 Complex, 03 medical and health sciences, Suppressor of Cytokine Signaling 1 Protein, SDG 3 - Good Health and Well-being, SUPPRESSOR, Actin-Related Protein 2-3 Complex/genetics, medicine, Humans, QH426, Whole genome sequencing, Science & Technology, Whole Genome Sequencing, Common variable immunodeficiency, DAS, Bayes Theorem, Immune dysregulation, Regulatory Sequences, Nucleic Acid/genetics, medicine.disease, RNA-Binding Proteins/genetics, STAT1 MUTATIONS, 030104 developmental biology, Primary immunodeficiency, IUIS PHENOTYPIC CLASSIFICATION, GAIN, 030215 immunology, Genome-Wide Association Study, Transcription Factors
Abstract: Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies1–3. Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1,318 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed4) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of—and interplay between—novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans. © 2020, The Author(s), under exclusive licence to Springer Nature Limited., Wellcome Trust, WT: 104807/Z/14/Z University College London, UCL: 100140/Z/12/Z, 107212/Z/15/Z, MR/L019027, 203141/Z/16/Z, 091157/Z/10/Z Bundesministerium für Bildung und Forschung, BMBF: 01ZX1306A University of Cambridge 201250/Z/16/Z 01ZX1709 Seventh Framework Programme, FP7 NIHR Bristol Biomedical Research Centre Deutsche Forschungsgemeinschaft, DFG Deutsche Forschungsgemeinschaft, DFG: EXC 2167-390884018 Juvenile Diabetes Research Foundation United Kingdom, JDRF: 9-2011-253, 5-SRA-2015-130-A-N National Institute for Health Research, NIHR: RG65966 Medical Research Council, MRC: RG95376, MR/L006197/1 Great Ormond Street Hospital for Children, GOSH, Acknowledgements The NBR-RD PID Consortium is part of the NIHR BioResource, for which funding was provided by the NIHR (NIHR, grant number RG65966). We acknowledge the participation of all NIHR BioResource volunteers, and thank the NIHR BioResource centre and staff for their contribution. J.E.D.T. is supported by the Medical Research Council (MRC) (RG95376 and MR/L006197/1); A.J.T. is supported by the Wellcome Trust (104807/Z/14/Z) and the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London; K.G.C.S. is supported by the MRC (programme grant MR/L019027) and is a Wellcome Investigator; A.J.C. was supported by the Wellcome Trust (091157/Z/10/Z, 107212/Z/15/Z, 100140/Z/12/Z, 203141/Z/16/Z), JDRF (9-2011-253, 5-SRA-2015-130-A-N), NIHR Oxford Biomedical Research Centre and NIHR Cambridge Biomedical Research Centre; E.E. has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement number 609020-Scientia Fellows; E.R. is supported by the Wellcome Trust (201250/Z/16/Z); D.E. is supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (SysInflame grant 01ZX1306A; GB-XMAP grant 01ZX1709) and funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) under Germany’s Excellence Strategy (EXC 2167-390884018). The NIHR Cambridge Biomedical Research Centre (BRC) is a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by the NIHR. This research was co-funded by the support listed above and the NIHR Cambridge BRC.
Published: 2020

19. Corrigendum: Common genetic variation drives molecular heterogeneity in human iPSCs

Author: Kilpinen, Helena, Goncalves, Angela, Leha, Andreas, Afzal, Vackar, Alasoo, Kaur, Ashford, Sofie, Bala, Sendu, Bensaddek, Dalila, Casale, Francesco Paolo, Culley, Oliver J., Danecek, Petr, Faulconbridge, Adam, Harrison, Peter W., Kathuria, Annie, McCarthy, Davis, McCarthy, Shane A., Meleckyte, Ruta, Memari, Yasin, Moens, Nathalie, Soares, Filipa, Mann, Alice, Streeter, Ian, Agu, Chukwuma A., Alderton, Alex, Nelson, Rachel, Harper, Sarah, Patel, Minal, White, Alistair, Patel, Sharad R., Clarke, Laura, Halai, Reena, Kirton, Christopher M., Kolb-Kokocinski, Anja, Beales, Philip, Birney, Ewan, Danovi, Davide, Lamond, Angus I., Ouwehand, Willem H., Vallier, Ludovic, Watt, Fiona M., Durbin, Richard, Stegle, Oliver, and Gaffney, Daniel J.
Subjects: Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Author(s): Helena Kilpinen; Angela Goncalves; Andreas Leha; Vackar Afzal; Kaur Alasoo; Sofie Ashford; Sendu Bala; Dalila Bensaddek; Francesco Paolo Casale; Oliver J. Culley; Petr Danecek; Adam Faulconbridge; Peter W. Harrison; [...]
Published: 2017
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20. Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes

Author: Whitworth, James, Smith, Philip S., Martin, Jose-Ezequiel, West, Hannah, Luchetti, Andrea, Rodger, Faye, Clark, Graeme, Carss, Keren, Stephens, Jonathan, Stirrups, Kathleen, Penkett, Chris, Mapeta, Rutendo, Ashford, Sofie, Megy, Karyn, Shakeel, Hassan, Ahmed, Munaza, Adlard, Julian, Barwell, Julian, Brewer, Carole, Casey, Ruth T., Armstrong, Ruth, Cole, Trevor, Evans, Dafydd Gareth, Fostira, Florentia, Greenhalgh, Lynn, Hanson, Helen, Henderson, Alex, Hoffman, Jonathan, Izatt, Louise, Kumar, Ajith, Kwong, Ava, Lalloo, Fiona, Ong, Kai Ren, Paterson, Joan, Park, Soo-Mi, Chen-Shtoyerman, Rakefet, Searle, Claire, Side, Lucy, Skytte, Anne-Bine, Snape, Katie, Woodward, Emma R., Tischkowitz, Marc D., and Maher, Eamonn R.
Subjects: Adult, Male, Genetic Variation, Middle Aged, inherited cancer genetics, Article, genetic testing, Neoplasms, Multiple Primary, Phenotype, whole-genome sequencing, cancer-predisposition syndromes, Biomarkers, Tumor, Humans, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Aged
Abstract: Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.
Published: 2018

21. Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations

Author: Lorenzini, Tiziana, primary, Fliegauf, Manfred, additional, Klammer, Nils, additional, Frede, Natalie, additional, Proietti, Michele, additional, Bulashevska, Alla, additional, Camacho-Ordonez, Nadezhda, additional, Varjosalo, Markku, additional, Kinnunen, Matias, additional, de Vries, Esther, additional, van der Meer, Jos W.M., additional, Ameratunga, Rohan, additional, Roifman, Chaim M., additional, Schejter, Yael D., additional, Kobbe, Robin, additional, Hautala, Timo, additional, Atschekzei, Faranaz, additional, Schmidt, Reinhold E., additional, Schröder, Claudia, additional, Stepensky, Polina, additional, Shadur, Bella, additional, Pedroza, Luis A., additional, van der Flier, Michiel, additional, Martínez-Gallo, Mónica, additional, Gonzalez-Granado, Luis Ignacio, additional, Allende, Luis M., additional, Shcherbina, Anna, additional, Kuzmenko, Natalia, additional, Zakharova, Victoria, additional, Neves, João Farela, additional, Svec, Peter, additional, Fischer, Ute, additional, Ip, Winnie, additional, Bartsch, Oliver, additional, Barış, Safa, additional, Klein, Christoph, additional, Geha, Raif, additional, Chou, Janet, additional, Alosaimi, Mohammed, additional, Weintraub, Lauren, additional, Boztug, Kaan, additional, Hirschmugl, Tatjana, additional, Dos Santos Vilela, Maria Marluce, additional, Holzinger, Dirk, additional, Seidl, Maximilian, additional, Lougaris, Vassilios, additional, Plebani, Alessandro, additional, Alsina, Laia, additional, Piquer-Gibert, Monica, additional, Deyà-Martínez, Angela, additional, Slade, Charlotte A., additional, Aghamohammadi, Asghar, additional, Abolhassani, Hassan, additional, Hammarström, Lennart, additional, Kuismin, Outi, additional, Helminen, Merja, additional, Allen, Hana Lango, additional, Thaventhiran, James E., additional, Freeman, Alexandra F., additional, Cook, Matthew, additional, Bakhtiar, Shahrzad, additional, Christiansen, Mette, additional, Cunningham-Rundles, Charlotte, additional, Patel, Niraj C., additional, Rae, William, additional, Niehues, Tim, additional, Brauer, Nina, additional, Syrjänen, Jaana, additional, Seppänen, Mikko R.J., additional, Burns, Siobhan O., additional, Tuijnenburg, Paul, additional, Kuijpers, Taco W., additional, Warnatz, Klaus, additional, Grimbacher, Bodo, additional, Adhya, Zoe, additional, Alachkar, Hana, additional, Anantharachagan, Ariharan, additional, Antrobus, Richard, additional, Arumugakani, Gururaj, additional, Ashford, Sofie, additional, Astle, William J., additional, Attwood, Anthony, additional, Bacchelli, Chiara, additional, Batista, Joana, additional, Baxendale, Helen E., additional, Bethune, Claire, additional, Bibi, Shahnaz, additional, Bleda, Marta, additional, Boardman, Barbara, additional, Booth, Claire, additional, Bradley, John R., additional, Breen, Gerome, additional, Brown, Matthew, additional, Browning, Michael J., additional, Brownlie, Mary, additional, Buckland, Matthew S., additional, Burren, Oliver S., additional, Carss, Keren, additional, Chambers, John, additional, Chandra, Anita, additional, Brod, Naomi Clements, additional, Clifford, Hayley, additional, Cooper, Nichola, additional, Daugherty, Louise C., additional, Davies, E.G., additional, Davies, Sophie, additional, Davis, John, additional, Deacock, Sarah, additional, Deevi, Sri V.V., additional, Dempster, John, additional, Devlin, Lisa A., additional, Dewhurst, Eleanor F., additional, Downes, Kate, additional, Drewe, Elizabeth, additional, Duarte, Daniel, additional, Edgar, J. David M., additional, Edwards, Karen, additional, Egner, William, additional, El-Shanawany, Tariq, additional, Erwood, Marie, additional, Fletcher, Debra, additional, Fox, James, additional, Frary, Amy J., additional, Frontini, Mattia, additional, Furnell, Abigail, additional, Gaspar, H. Bobby, additional, Ghurye, Rohit, additional, Gilmour, Kimberly C., additional, Gleadall, Nicholas S., additional, Goddard, Sarah, additional, Gordins, Pavels, additional, Gräf, Stefan, additional, Grassi, Luigi, additional, Greene, Daniel, additional, Grigoriadou, Sofia, additional, Hackett, Scott, additional, Hague, Rosie, additional, Haimel, Matthias, additional, Harper, Lorraine, additional, Hayman, Grant, additional, Herwadkar, Archana, additional, Hu, Fengyuan, additional, Hughes, Stephen, additional, Huissoon, Aarnoud P., additional, James, Roger, additional, Jolles, Stephen, additional, Jolley, Jennifer, additional, Jones, Julie, additional, Karim, Yousuf, additional, Kasanicki, Mary A., additional, Kelleher, Peter, additional, Kempster, Carly, additional, Kiani, Sorena, additional, Kingston, Nathalie, additional, Klein, Nigel, additional, Kostadima, Myrto, additional, Kreuzhuber, Roman, additional, Kumararatne, Dinakantha, additional, Laffan, James, additional, Lear, Sara E., additional, Linger, Rachel, additional, Longhurst, Hilary, additional, Lorenzo, Lorena E., additional, Lyons, Paul A., additional, Maimaris, Jesmeen, additional, Manson, Ania, additional, Mapeta, Rutendo, additional, Martin, Jennifer, additional, McCarthy, Mark I., additional, McDermott, Elizabeth M., additional, McKinney, Harriet, additional, Meacham, Stuart, additional, Megy, Karyn, additional, Millar, Hazel, additional, Mistry, Anoop, additional, Morrisson, Valerie, additional, Murng, Sai H.K., additional, Nasir, Iman, additional, Nejentsev, Sergey, additional, Noorani, Sadia, additional, Oksenhendler, Eric, additional, Ouwehand, Willem H., additional, Papadia, Sofia, additional, Penkett, Christopher J., additional, Petersen, Romina, additional, Ponsford, Mark J., additional, Qasim, Waseem, additional, Quinn, Ellen, additional, Quinti, Isabella, additional, Raymond, F. Lucy, additional, Rayner-Matthews, Paula J., additional, Richter, Alex, additional, Samani, Nilesh, additional, Samarghitean, Crina, additional, Sanchis-Juan, Alba, additional, Sargur, Ravishankar B., additional, Savic, Sinisa, additional, Seneviratne, Suranjith L., additional, Sewell, W.A. Carrock, additional, Seyres, Denis, additional, Shackley, Fiona, additional, Shamardina, Olga, additional, Simeoni, Ilenia, additional, Simpson, Michael A., additional, Smith, Kenneth G.C., additional, Staines, Simon, additional, Staples, Emily, additional, Stark, Hannah, additional, Stauss, Hans, additional, Steele, Cathal L., additional, Stephens, Jonathan, additional, Stirrups, Kathleen E., additional, Thomas, David, additional, Thomas, Moira J., additional, Thomas, Patrick, additional, Thrasher, Adrian J., additional, Tilly, Tobias, additional, Titterton, Catherine, additional, Treadaway, Paul, additional, Tuna, Salih, additional, Turro, Ernest, additional, Urniaz, Rafal, additional, von Ziegenweidt, Julie, additional, Walker, Neil, additional, Watt, Christopher, additional, Welch, Steven B., additional, Whitehorn, Deborah, additional, Willcocks, Lisa, additional, Wood, Nicholas, additional, Wood, Yvette, additional, Workman, Sarita, additional, Worth, Austen, additional, Yates, Katherine, additional, Yeatman, Nigel, additional, Yong, Patrick F.K., additional, Young, Timothy, additional, Yu, Ping, additional, and Zlamalova, Eliska, additional
Published: 2020
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22. Platelet function is modified by common sequence variation in megakaryocyte super enhancers

Author: Petersen, Romina, Lambourne, John J., Javierre, Biola M., Grassi, Luigi, Kreuzhuber, Roman, Ruklisa, Dace, Rosa, Isabel M., Tomé, Ana R., Elding, Heather, van Geffen, Johanna P., Jiang, Tao, Farrow, Samantha, Cairns, Jonathan, Al-Subaie, Abeer M., Ashford, Sofie, Attwood, Antony, Batista, Joana, Bouman, Heleen, Burden, Frances, Choudry, Fizzah A., Clarke, Laura, Flicek, Paul, Garner, Stephen F., Haimel, Matthias, Kempster, Carly, Ladopoulos, Vasileios, Lenaerts, An-Sofie, Materek, Paulina M., McKinney, Harriet, Meacham, Stuart, Mead, Daniel, Nagy, Magdolna, Penkett, Christopher J., Rendon, Augusto, Seyres, Denis, Sun, Benjamin, Tuna, Salih, van der Weide, Marie-Elise, Wingett, Steven W., Martens, Joost H., Stegle, Oliver, Richardson, Sylvia, Vallier, Ludovic, Roberts, David J., Freson, Kathleen, Wernisch, Lorenz, Stunnenberg, Hendrik G., Danesh, John, Fraser, Peter, Soranzo, Nicole, Butterworth, Adam S., Heemskerk, Johan W., Turro, Ernest, Spivakov, Mikhail, Ouwehand, Willem H., Astle, William J., Downes, Kate, Kostadima, Myrto, Frontini, Mattia, Lambourne, John [0000-0003-2460-0759], Grassi, Luigi [0000-0002-6308-7540], Haimel, Matthias [0000-0002-0320-0214], Rendon Restrepo, Augusto [0000-0001-8994-0039], Seyres, Denis [0000-0002-2066-6980], Sun, Ben [0000-0001-6347-2281], Tuna, Salih [0000-0003-3606-4367], Richardson, Sylvia [0000-0003-1998-492X], Vallier, Ludovic [0000-0002-3848-2602], Danesh, John [0000-0003-1158-6791], Soranzo, Nicole [0000-0003-1095-3852], Butterworth, Adam [0000-0002-6915-9015], Turro Bassols, Ernest [0000-0002-1820-6563], Ouwehand, Willem [0000-0002-7744-1790], Astle, William [0000-0001-8866-6672], Downes, Kate [0000-0003-0366-1579], Frontini, Mattia [0000-0001-8074-6299], Apollo - University of Cambridge Repository, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: CARIM - R1.03 - Cell biochemistry of thrombosis and haemostasis, and Biochemie
Subjects: Blood Platelets, GENE-REGULATION, BLOOD, Erythroblasts, Science, Genetic Variation, OPEN CHROMATIN, DISEASE, Article, Chromatin, DNA-BINDING PROTEINS, THROMBUS FORMATION, GENOME, HUMAN CELL-TYPES, SEQ, Enhancer Elements, Genetic, TRAIT LOCI, Humans, Promoter Regions, Genetic, Megakaryocytes
Abstract: Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through ex vivo and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions., Numerous genetic variants, including those located in the non-coding regions of the genome, are known to be associated with blood cells traits. Here, Frontini and colleagues investigate their potential regulatory functions using epigenomic data and promoter long-range interactions.
Published: 2017

23. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Author: Hendricks, Audrey E., Bochukova, Elena G., Marenne, Gaëlle, Keogh, Julia M., Atanassova, Neli, Bounds, Rebecca, Wheeler, Eleanor, Mistry, Vanisha, Henning, Elana, Körner, Antje, Muddyman, Dawn, McCarthy, Shane, Hinney, Anke, Hebebrand, Johannes, Scott, Robert A., Langenberg, Claudia, Wareham, Nick J., Surendran, Praveen, Howson, Joanna M M, Butterworth, Adam S., Danesh, John, Nordestgaard, Børge G., Nielsen, Sune F., Afzal, Shoaib, Papadia, Sofia, Ashford, Sofie, Garg, Sumedha, Millhauser, Glenn L., Palomino, Rafael I., Kwasniewska, Alexandra, Tachmazidou, Ioanna, O'Rahilly, Stephen, Zeggini, Eleftheria, Barroso, Inês, Farooqi, I. Sadaf, Benzeval, Michaela, Burton, Jonathan, Buck, Nicholas, Jäckle, Annette, Kumari, Meena, Laurie, Heather, Lynn, Peter, Pudney, Stephen, Rabe, Birgitta, Wolke, Dieter, Overvad, Kim, Tjønneland, Anne, Clavel-Chapelon, Francoise, Kaaks, Rudolf, Boeing, Heiner, Trichopoulou, Antonia, Ferrari, Pietro, Palli, Domenico, Krogha, Vittorio, Panico, Salvatore, Tuminoa, Rosario, Matullo, Giuseppe, Boer, Jolanda Ma, Van Der Schouw, Yvonne, Weiderpass, Elisabete, Quiros, J. Ramon, Sánchez, María José, Navarro, Carmen, Moreno-Iribas, Conchi, Arriola, Larraitz, Melander, Olle, Wennberg, Patrik, Key, Timothy J., Riboli, Elio, Al-Turki, Saeed, Anderson, Carl A, Anney, Richard, Antony, Dinu, Soler Artigas, María, Ayub, Muhammad, Bala, Senduran, Barrett, Jeffrey C, Beales, Phil, Bentham, Jamie, Bhattacharyaa, Shoumo, Birney, Ewan, Blackwooda, Douglas, Bobrow, Martin, Bolton, Patrick F., Boustred, Chris, Breen, Gerome, Calissanoa, Mattia, Carss, Keren, Charlton, Ruth, Chatterjee, Krishna, Chen, Lu, Ciampia, Antonio, Cirak, Sebahattin, Clapham, Peter, Clement, Gail, Coates, Guy, Coccaa, Massimiliano, Collier, David A, Cosgrove, Catherine, Coxa, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Danecek, Petr, Day, Ian N M, Day-Williams, Aaron G, Dominiczak, Anna, Down, Thomas, Du, Yuanping, Dunham, Ian, Durbin, Richard, Edkins, Sarah, Ekong, Rosemary, Ellis, Peter, Evansa, David M., FitzPatrick, David R., Flicek, Paul, Floyd, James S., Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Gallagher, Louise, Gaunt, Tom R., Geihs, Matthias, Geschwind, Daniel H., Greenwood, Celia M.T., Griffin, Heather, Grozeva, Detelina, Guo, Xiaosen, Guo, Xueqin, Gurling, Hugh, Hart, Deborah J., Holmans, Peter A, Howie, Bryan, Huang, Jie, Huang, Liren, Hubbard, Tim, Humphries, Steve E., Hurles, Matthew E., Hysi, Pirro G., Iotchkova, Valentina, Jackson, David K., Jamshidi, Yalda, Joyce, Chris, Karczewski, Konrad J., Kaye, Jane, Keane, Thomas, Kemp, John P., Kennedy, Karen, Kent, Alastair, Khawaja, Farrah, Van Kogelenberg, Margriet, Kolb-Kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Lek, Monkol, Li, Rui, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Lönnqvist, Jouko, Lopes, Luis R., Lopes, Margarida, MacArthur, Daniel G., Mangino, Massimo, Marchini, Jonathan, Maslen, John, Mathieson, Iain, McGuffin, Peter, McIntosh, Andrew M., McKechanie, Andrew G., McQuillin, Andrew, Memari, Yasin, Metrustry, Sarah, Migone, Nicola, Min, Josine L., Mitchison, Hannah M, Moayyeri, Alireza, Morris, Andrew D., Morris, James, Muntoni, Francesco, Northstone, Kate, O'Donovan, Michael C., Onoufriadis, Alexandros, Oualkacha, Karim, Owen, Michael J, Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R., Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Payne, Stewart J., Perry, John R. B., Pietilainen, Olli, Plagnol, Vincent, Pollitt, Rebecca C., Porteous, David J., Povey, Sue, Quail, Michael A., Quaye, Lydia, Raymond, F. Lucy, Rehnström, Karola, Richards, J Brent, Ridout, Cheryl K., Ring, Susan M., Ritchie, Graham R.S., Roberts, Nicola, Robinson, Rachel L., Savage, David B., Scambler, Peter, Schiffels, Stephan, Schmidts, Miriam, Schoenmakers, Nadia, Scott, Richard H., Semple, Robert K., Serra, Eva, Sharp, Sally I., Shaw, Adam, Shihab, Hashem A., Shin, So Youn, Skuse, David, Small, Kerrin S, Smee, Carol, Smith, Blair H., Davey Smith, George, Soranzo, Nicole, Southam, Lorraine, Spasic-Boskovic, Olivera, Spector, Timothy D, St Clair, David, St Pourcain, Beate, Stalker, Jim, Stevens, Elizabeth, Sun, Jianping, Surdulescu, Gabriela L, Suvisaari, Jaana, Syrris, Petros, Taylor, Rohan, Tian, Jing, Timpson, Nicholas J., Tobin, Martin D, Valdes, Ana M., Vandersteen, Anthony M., Vijayarangakannan, Parthiban, Visscher, Peter M., Wain, Louise V., Walter, Klaudia, Walters, James T.R., Wang, Guangbiao, Wang, Jun, Wang, Nai-Yu, Ward, Kirsten, Whyte, Tamieka, Williams, Hywel J., Williamson, Kathleen A., Wilson, Crispian, Wilson, Scott G., Wong, Kim, Xu, Changjiang, Yang, Jian, Zhang, Feng, Zhang, Pingbo, Zheng, Hou Feng, Hendricks, Audrey E., Bochukova, Elena G., Marenne, Gaã«lle, Keogh, Julia M., Atanassova, Neli, Bounds, Rebecca, Wheeler, Eleanor, Mistry, Vanisha, Henning, Elana, Kã¶rner, Antje, Muddyman, Dawn, Mccarthy, Shane, Hinney, Anke, Hebebrand, Johanne, Scott, Robert A., Langenberg, Claudia, Wareham, Nick J., Surendran, Praveen, Howson, Joanna M., Butterworth, Adam S., Danesh, John, Nordestgaard, Bã¸rge G, Nielsen, Sune F, Afzal, Shoaib, Papadia, Sofia, Ashford, Sofie, Garg, Sumedha, Millhauser, Glenn L., Palomino, Rafael I., Kwasniewska, Alexandra, Tachmazidou, Ioanna, O'Rahilly, Stephen, Zeggini, Eleftheria, Barroso, Inãª, Farooqi, I. Sadaf, Benzeval, Michaela, Burton, Jonathan, Buck, Nichola, Jã¤ckle, Annette, Kumari, Meena, Laurie, Heather, Lynn, Peter, Pudney, Stephen, Rabe, Birgitta, Wolke, Dieter, Overvad, Kim, Tjã¸nneland, Anne, Clavel chapelon, Francoise, Kaaks, Rudolf, Boeing, Heiner, Trichopoulou, Antonia, Ferrari, Pietro, Palli, Domenico, Krogha, Vittorio, Panico, Salvatore, Tuminoa, Rosario, Matullo, Giuseppe, Boer, Jolanda, Van Der Schouw, Yvonne, Weiderpass, Elisabete, Quiros, J. Ramon, Sã¡nchez, Marãa josã©, Navarro, Carmen, Moreno iribas, Conchi, Arriola, Larraitz, Melander, Olle, Wennberg, Patrik, Key, Timothy J., Riboli, Elio, Turki, Saeed Al, Anderson, Carl A., Anney, Richard, Antony, Dinu, Soler Artigas, Marãa, Ayub, Muhammad, Bala, Senduran, Barrett, Jeffrey C., Beales, Phil, Bentham, Jamie, Bhattacharyaa, Shoumo, Birney, Ewan, Blackwooda, Dougla, Bobrow, Martin, Bolton, Patrick F., Boustred, Chri, Breen, Gerome, Calissanoa, Mattia, Carss, Keren, Charlton, Ruth, Chatterjee, Krishna, Chen, Lu, Ciampia, Antonio, Cirak, Sebahattin, Clapham, Peter, Clement, Gail, Coates, Guy, Coccaa, Massimiliano, Collier, David A., Cosgrove, Catherine, Coxa, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Danecek, Petr, Day, Ian N. M., Day williams, Aaron, Dominiczak, Anna, Down, Thoma, Du, Yuanping, Dunham, Ian, Durbin, Richard, Edkins, Sarah, Ekong, Rosemary, Ellis, Peter, Evansa, David M., Fitzpatrick, David R., Flicek, Paul, Floyd, Jame, Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Gallagher, Louise, Gaunt, Tom R., Geihs, Matthia, Geschwind, Daniel, Greenwood, Celia M. T., Griffin, Heather, Grozeva, Detelina, Guo, Xiaosen, Guo, Xueqin, Gurling, Hugh, Hart, Deborah, Holmans, Peter, Howie, Bryan, Huang, Jie, Huang, Liren, Hubbard, Tim, Humphries, Steve E., Hurles, Matthew E., Hysi, Pirro, Iotchkova, Valentina, Jackson, David K., Jamshidi, Yalda, Joyce, Chri, Karczewski, Konrad J., Kaye, Jane, Keane, Thoma, Kemp, John P., Kennedy, Karen, Kent, Alastair, Khawaja, Farrah, Van Kogelenberg, Margriet, Kolb kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Lek, Monkol, Li, Rui, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Lã¶nnqvist, Jouko, Lopes, Luis R., Lopes, Margarida, Macarthur, Daniel G., Mangino, Massimo, Marchini, Jonathan, Maslen, John, Mathieson, Iain, Mcguffin, Peter, Mcintosh, Andrew M., Mckechanie, Andrew G., Mcquillin, Andrew, Memari, Yasin, Metrustry, Sarah, Migone, Nicola, Min, Josine L., Mitchison, Hannah M., Moayyeri, Alireza, Morris, Andrew, Morris, Jame, Muntoni, Francesco, Northstone, Kate, O'Donovan, Michael C., Onoufriadis, Alexandro, Oualkacha, Karim, Owen, Michael J., Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R., Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Payne, Stewart J., Perry, John R. B., Pietilainen, Olli, Plagnol, Vincent, Pollitt, Rebecca C., Porteous, David J., Povey, Sue, Quail, Michael A., Quaye, Lydia, Raymond, F. Lucy, Rehnstrã¶m, Karola, Richards, J. Brent, Ridout, Cheryl K., Ring, Susan, Ritchie, Graham R. S., Roberts, Nicola, Robinson, Rachel L., Savage, David B., Scambler, Peter, Schiffels, Stephan, Schmidts, Miriam, Schoenmakers, Nadia, Scott, Richard H., Semple, Robert K., Serra, Eva, Sharp, Sally I., Shaw, Adam, Shihab, Hashem A., Shin, So youn, Skuse, David, Small, Kerrin S., Smee, Carol, Smith, Blair H., Davey Smith, George, Soranzo, Nicole, Southam, Lorraine, Spasic boskovic, Olivera, Spector, Timothy D., St Clair, David, St Pourcain, Beate, Stalker, Jim, Stevens, Elizabeth, Sun, Jianping, Surdulescu, Gabriela, Suvisaari, Jaana, Syrris, Petro, Taylor, Rohan, Tian, Jing, Timpson, Nicholas J., Tobin, Martin D., Valdes, Ana M., Vandersteen, Anthony M., Vijayarangakannan, Parthiban, Visscher, Peter M., Wain, Louise V., Walter, Klaudia, Walters, James T. R., Wang, Guangbiao, Wang, Jun, Wang, Yu, Ward, Kirsten, Whyte, Tamieka, Williams, Hywel J., Williamson, Kathleen A., Wilson, Crispian, Wilson, Scott G., Wong, Kim, Xu, Changjiang, Yang, Jian, Zhang, Feng, Zhang, Pingbo, and Zheng, Hou feng
Subjects: Multidisciplinary, Journal Article, General
Abstract: Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as describedw previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.
Published: 2017

24. Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Author: Rhodes, Christopher J, Batai, Ken, Bleda, Marta, Haimel, Matthias, Southgate, Laura, Germain, Marine, Pauciulo, Michael W, Hadinnapola, Charaka, Aman, Jurjan, Girerd, Barbara, Arora, Amit, Knight, Jo, Hanscombe, Ken B, Karnes, Jason H, Kaakinen, Marika, Gall, Henning, Ulrich, Anna, Harbaum, Lars, Cebola, Ines, Ferrer, Jorge, Lutz, Katie, Swietlik, Emilia M, Ahmad, Ferhaan, Amouyel, Philippe, Archer, Stephen L, Argula, Rahul, Austin, Eric D, Badesch, David, Bakshi, Sahil, Barnett, Christopher, Benza, Raymond, Bhatt, Nitin, Bogaard, Harm J, Burger, Charles D, Chakinala, Murali, Church, Colin, Coghlan, John G, Condliffe, Robin, Corris, Paul A, Danesino, Cesare, Debette, Stephanie, Elliott, C Gregory, Elwing, Jean, Eyries, Melanie, Fortin, Terry, Franke, Andre, Frantz, Robert P, Frost, Adaani, Garcia, Joe GN, Ghio, Stefano, Ghofrani, Hossein-Ardeschir, Gibbs, J Simon R, Harley, John, He, Hua, Hill, Nicholas S, Hirsch, Russel, Houweling, Arjan C, Howard, Luke S, Ivy, Dunbar, Kiely, David G, Klinger, James, Kovacs, Gabor, Lahm, Tim, Laudes, Matthias, Machado, Rajiv D, Ross, Robert V MacKenzie, Marsolo, Keith, Martin, Lisa J, Moledina, Shahin, Montani, David, Nathan, Steven D, Newnham, Michael, Olschewski, Andrea, Olschewski, Horst, Oudiz, Ronald J, Ouwehand, Willem H, Peacock, Andrew J, Pepke-Zaba, Joanna, Rehman, Zia, Robbins, Ivan, Roden, Dan M, Rosenzweig, Erika B, Saydain, Ghulam, Scelsi, Laura, Schilz, Robert, Seeger, Werner, Shaffer, Christian M, Simms, Robert W, Simon, Marc, Sitbon, Olivier, Suntharalingam, Jay, Tang, Haiyang, Tchourbanov, Alexander Y, Thenappan, Thenappan, Torres, Fernando, Toshner, Mark R, Treacy, Carmen M, Noordegraaf, Anton Vonk, Waisfisz, Quinten, Walsworth, Anna K, Walter, Robert E, Wharton, John, White, R James, Wilt, Jeffrey, Wort, Stephen J, Yung, Delphine, Lawrie, Allan, Humbert, Marc, Soubrier, Florent, Tregouet, David-Alexandre, Prokopenko, Inga, Kittles, Richard, Graf, Stefan, Nichols, William C, Trembath, Richard C, Desai, Ankit A, Morrell, Nicholas W, Wilkins, Martin R, Adlard, Julian, Ahmed, Munaza, Aitman, Tim, Alachkar, Hana, Allsup, David, Almeida-King, Jeff, Ancliff, Philip, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Ashford, Sofie, Astle, William, Attwood, Anthony, Babbs, Chris, Bakchoul, Tamam, Bariana, Tadbir, Barwell, Julian, Bennett, David, Bentley, David, Bierzynska, Agnieszka, Biss, Tina, Bogaard, Harm, Bourne, Christian, Boyce, Sara, Bradley, John, Breen, Gerome, Brennan, Paul, Brewer, Carole, Brown, Matthew, Browning, Michael, Buchan, Rachel, Buckland, Matthew, Bueser, Teofila, Burns, Siobhan, Burren, Oliver, Calleja, Paul, Carr-White, Gerald, Carss, Keren, Casey, Ruth, Caulfield, Mark, Chambers, John, Chambers, Jennifer, Cheng, Floria, Chinnery, Patrick F, Christian, Martin, Brod, Naomi Clements, Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor, Collins, Janine, Collins, Peter, Colombo, Camilla, Cook, Stuart, Cook, Terry, Cooper, Nichola, Corris, Paul, Crisp-Hihn, Abigail, Curry, Nicola, Daniels, Matthew, Daugherty, Louise, Davis, John, Deevi, Sri VV, Dent, Timothy, Dewhurst, Eleanor, Dixon, Peter, Downes, Kate, Drazyk, Anna, Drewe, Elizabeth, Dutt, Tina, Edgar, David, Edwards, Karen, Egner, William, Erber, Wendy, Erwood, Marie, Estiu, Maria C, Evans, Gillian, Evans, Dafydd Gareth, Everington, Tamara, Eyries, Mlanie, Favier, Remi, Fletcher, Debra, Fox, James, Frary, Amy, French, Courtney, Freson, Kathleen, Frontini, Mattia, Gale, Daniel, Geoghegan, Claire, Gerighty, Terry, Gibbs, Simon, Gilmour, Kimberley, Goddard, Sarah, Gomez, Keith, Gordins, Pavels, Gosal, David, Grassi, Luigi, Greene, Daniel, Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip, Grigoriadou, Sofia, Grocock, Russell, Grozeva, Detelina, Hackett, Scott, Hague, William, Hall, Matthew, Hanson, Helen, Harkness, Kirsty, Harper, Andrew, Harris, Claire, Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Henderson, Alex, Hoffmann, Jonathan, Horvath, Rita, Houweling, Arjan, Howard, Luke, Hu, Fengyuan, Hudson, Gavin, Hughes, Joseph, Huissoon, Aarnoud, Humphray, Sean, Hunter, Sarah, Hurles, Matthew, Izatt, Louise, James, Roger, Johnson, Sally, Jolles, Stephen, Jolley, Jennifer, Jurkute, Neringa, Kasanicki, Mary, Kazkaz, Hanadi, Kazmi, Rashid, Kelleher, Peter, Kiely, David, Kingston, Nathalie, Klima, Robert, Kostadima, Myrto, Koziell, Ania, Kreuzhuber, Roman, Kuijpers, Taco, Kumar, Ajith, Kumararatne, Dinakantha, Kurian, Manju, Laffan, Michael, Lalloo, Fiona, Lambert, Michele, Allen, Hana Lango, Layton, Mark, Lentaigne, Claire, Levine, Adam, Linger, Rachel, Longhurst, Hilary, Louka, Eleni, Ross, Robert MacKenzie, Madan, Bella, Maher, Eamonn, Maimaris, Jesmeen, Mangles, Sarah, Mapeta, Rutendo, Marchbank, Kevin, Marks, Stephen, Markus, Hugh S, Marschall, Hanns-Ulrich, Marshall, Andrew, Martin, Jennifer, Mathias, Mary, Matthews, Emma, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark, Meacham, Stuart, Mead, Adam, Megy, Karyn, Mehta, Sarju, Michaelides, Michel, Millar, Carolyn, Moore, Tony, Morrell, Nicholas, Mozere, Monika, Muir, Keith, Mumford, Andrew, O'Sullivan, Jennifer, Obaji, Samya, Okoli, Steven, Ong, Kai Ren, Ormondroyd, Elizabeth, Ouwehand, Willem, Papadia, Sofia, Park, Soo-Mi, Parry, David, Paterson, Joan, Peacock, Andrew, Peden, John, Peerlinck, Kathelijne, Penkett, Christopher, Petersen, Romina, Pyle, Angela, Rankin, Stuart, Rao, Anupama, Raymond, F Lucy, Rayner-Matthews, Paula, Rees, Christine, Rendon, Augusto, Renton, Tara, Rice, Andrew, Richardson, Sylvia, Richter, Alex, Roberts, Irene, Roughley, Catherine, Roy, Noemi, Sadeghi-Alavijeh, Omid, Saleem, Moin, Samani, Nilesh, Sanchis-Juan, Alba, Sargur, Ravishankar, Satchell, Simon, Savic, Sinisa, Schulman, Sol, Scully, Marie, Searle, Claire, Sewell, Carrock, Seyres, Denis, Shapiro, Susie, Sharmardina, Olga, Shtoyerman, Rakefet, Sibson, Keith, Side, Lucy, Simeoni, Ilenia, Simpson, Michael, Sivapalaratnam, Suthesh, Skytte, Anne-Bine, Smith, Katherine, Smith, Kenneth GC, Snape, Katie, Staines, Simon, Staples, Emily, Stark, Hannah, Stephens, Jonathan, Stirrups, Kathleen, Stock, Sophie, Swietlik, Emilia, Tait, R Campbell, Talks, Kate, Tan, Rhea, Thaventhiran, James, Themistocleous, Andreas, Thomas, Moira, Thomson, Kate, Thrasher, Adrian, Thys, Chantal, Tischkowitz, Marc, Titterton, Catherine, Toh, Cheng-Hock, Toshner, Mark, Traylor, Matthew, Treacy, Carmen, Trembath, Richard, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Vale, Tom, Van Geet, Chris, Van Zuydam, Natalie, Vazquez-Lopez, Marta, Von Ziegenweidt, Julie, Waisfisz, Quintin, Walker, Suellen, Ware, James, Watkins, Hugh, Watt, Christopher, Webster, Andrew, Wei, Wei, Welch, Steven, Wessels, Julie, Westbury, Sarah, Westwood, John-Paul, Whitehorn, Deborah, Whitworth, James, Williamson, Catherine, Wong, Edwin, Wood, Nicholas, Wood, Yvette, Woods, Geoff, Woodward, Emma, Wort, Stephen, Worth, Austen, Yates, Katherine, Yong, Patrick, Young, Tim, Yu, Ping, Yu-Wai-Man, Patrick, Theuer, Alison, Malur, Anagha, Williams, Ann, Dotson, Anne, Warden, Ashley, Harrington, Brandy, Vang, Brenda, Ziemak, Caitlin, Casanova, Nancy, Caskey, Elizabeth, MacDonald, Catherine, Rowley, Courtney, Larimore, Daniel, Brady, Daniela, Tomer, David, Davis, Anne, Broach, Debra, Devereux, Jane, Lovato, Ellen, Stratton, Eric, Turk, Erin, Jackson, Esperanza, Paciotti, Gina, Peichel, Gretchen, Birru, Hellina, del Junco, Holly, Ingledue, Rebecca, Bruno, Jackie, Drake, Jan, Marks, Jennifer, Pisarcik, Jessica, Spears, Jill, Santiago, Joseph, DeMartino, Jordyn, Beckmann, Joy, Palmer, Julia, Visnaw, Karen, Kennedy, Karla, Lewis, Karlise, Miller-Reed, Kathleen, Hannon, Kelly, McClain, Kimberly, Dillon, Laura, Olanipekun, Lekan, Mendibles, Lillian, Hawke, Lindsey, Brody, Linnea, Durst, Louise, Andrews, Mary, Allahua, Melissa, Stratoberdha, Melissa, Lemma, Merte, Cope, Molly, Franzo, Mya, Feliz, Natalia, Hawkes, Nicholas, Norwood, Tracy, Wilson, Opal, Palmisciano, Amy, Gruhlke, Peggy, Correa, Priscilla, Blake, Randy, Karnekar, Reema, Do, Robyn, Rohwer, Kristal, Ahmed, Sara, Schiltz, Kimberly, Scovel, Page, Cordell, Shannon, Heuerman, Sharon, Ahmad, Shazzra, Szuberla, Sylwia, Roads, Tammy, Iem, Thoeun, Mcgaha, Traci, Urban, Tracy, Aston, Valerie, Ayesh, Waleed, Light, Allison, Arkon, Abby, Tavlarides, Andrea, Anderson, Audrey, Bindu, John, Boekwig, Deedre, Singleton, Donna, Abrea, Inna, Lee, Jennifer, Ormiston, Mark, Whitman, Renesa, Holy, Royanne, Almeida-Peters, Sisama, Igenoza, Tosin, Farber, Hap, Reponen, Auvo, Barve, Mukta, Gygi, Amber, and Winslow, Clayborne
Subjects: ALPHA, Science & Technology, Critical Care Medicine, ENDODERM FORMATION, General & Internal Medicine, Respiratory System, SUSCEPTIBILITY, SOX17, Life Sciences & Biomedicine, DISEASE
Abstract: BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. FINDINGS: A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity. INTERPRETATION: This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. FUNDING: UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR. ispartof: LANCET RESPIRATORY MEDICINE vol:7 issue:3 pages:227-238 ispartof: location:England status: published
Published: 2019

25. Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data (vol 8, 1300, 2018)

Author: Farmery, James HR, Smith, Mike L, Lynch, Andy G, Huissoon, Aarnoud, Furnell, Abigail, Mead, Adam, Levine, Adam P, Manzur, Adnan, Thrasher, Adrian, Greenhalgh, Alan, Parker, Alasdair, Sanchis-Juan, Alba, Richter, Alex, Gardham, Alice, Lawrie, Allan, Sohal, Aman, Creaser-Myers, Amanda, Frary, Amy, Greinacher, Andreas, Themistocleous, Andreas, Peacock, Andrew J, Marshall, Andrew, Mumford, Andrew, Rice, Andrew, Webster, Andrew, Brady, Angie, Koziell, Ania, Manson, Ania, Chandra, Anita, Hensiek, Anke, in't Veld, Anna Huis, Maw, Anna, Kelly, Anne M, Moore, Anthony, Noordegraaf, Anton Vonk, Attwood, Antony, Herwadkar, Archana, Ghofrani, Ardi, Houweling, Arjan C, Girerd, Barbara, Furie, Bruce, Treacy, Carmen M, Millar, Carolyn M, Sewell, Carrock, Roughley, Catherine, Titterton, Catherine, Williamson, Catherine, Hadinnapola, Charaka, Deshpande, Charu, Toh, Cheng-Hock, Bacchelli, Chiara, Patch, Chris, Van Geet, Chris, Babbs, Christian, Bryson, Christine, Penkett, Christopher J, Rhodes, Christopher J, Watt, Christopher, Bethune, Claire, Booth, Claire, Lentaigne, Claire, McJannet, Coleen, Church, Colin, French, Courtney, Samarghitean, Crina, Halmagyi, Csaba, Gale, Daniel, Greene, Daniel, Hart, Daniel, Allsup, David, Bennett, David, Edgar, David, Kiely, David G, Gosal, David, Perry, David J, Keeling, David, Montani, David, Shipley, Debbie, Whitehorn, Deborah, Fletcher, Debra, Krishnakumar, Deepa, Grozeva, Detelina, Kumararatne, Dinakantha, Thompson, Dorothy, Josifova, Dragana, Maher, Eamonn, Wong, Edwin KS, Murphy, Elaine, Dewhurst, Eleanor, Louka, Eleni, Rosser, Elisabeth, Chalmers, Elizabeth, Colby, Elizabeth, Drewe, Elizabeth, McDermott, Elizabeth, Thomas, Ellen, Staples, Emily, Clement, Emma, Matthews, Emma, Wakeling, Emma, Oksenhendler, Eric, Turro, Ernest, Reid, Evan, Wassmer, Evangeline, Raymond, F Lucy, Hu, Fengyuan, Kennedy, Fiona, Soubrier, Florent, Flinter, Frances, Kovacs, Gabor, Polwarth, Gary, Ambegaonkar, Gautum, Arno, Gavin, Hudson, Gavin, Woods, Geoff, Coghlan, Gerry, Hayman, Grant, Arumugakani, Gururaj, Schotte, Gwen, Cook, H Terry, Alachkar, Hana, Allen, Hana Lango, Lango-Allen, Hana, Stark, Hannah, Stauss, Hans, Schulze, Harald, Boggard, Harm J, Baxendale, Helen, Dolling, Helen, Firth, Helen, Gall, Henning, Watson, Henry, Longhurst, Hilary, Markus, Hugh S, Watkins, Hugh, Simeoni, Ilenia, Emmerson, Ingrid, Roberts, Irene, Quinti, Isabella, Wanjiku, Ivy, Gibbs, J Simon R, Thaventhiran, James, Whitworth, James, Hurst, Jane, Collins, Janine, Suntharalingam, Jay, Payne, Jeanette, Thachil, Jecko, Martin, Jennifer M, Martin, Jennifer, Carmichael, Jenny, Maimaris, Jesmeen, Paterson, Joan, Pepke-Zaba, Joanna, Heemskerk, Johan WM, Gebhart, Johanna, Davis, John, Pasi, John, Bradley, John R, Wharton, John, Stephens, Jonathan, Rankin, Julia, Anderson, Julie, Vogt, Julie, von Ziegenweldt, Julie, Rehnstrom, Karola, Megy, Karyn, Talks, Kate, Peerlinck, Kathelijne, Yates, Katherine, Freson, Kathleen, Stirrups, Kathleen, Gomez, Keith, Smith, Kenneth GC, Carss, Keren, Rue-Albrecht, Kevin, Gilmour, Kimberley, Masati, Larahmie, Scelsi, Laura, Southgate, Laura, Ranganathan, Lavanya, Ginsberg, Lionel, Devlin, Lisa, Willcocks, Lisa, Ormondroyd, Liz, Lorenzo, Lorena, Harper, Lorraine, Allen, Louise, Daugherty, Louise, Chitre, Manali, Kurian, Manju, Humbert, Marc, Tischkowitz, Marc, Bitner-Glindzicz, Maria, Erwood, Marie, Scully, Marie, Veltman, Marijke, Caulfield, Mark, Layton, Mark, McCarthy, Mark, Ponsford, Mark, Toshner, Mark, Bleda, Marta, Wilkins, Martin, Mathias, Mary, Reilly, Mary, Afzal, Maryam, Brown, Matthew, Rondina, Matthew, Stubbs, Matthew, Haimel, Matthias, Lees, Melissa, Laffan, Michael A, Browning, Michael, Gattens, Michael, Richards, Michael, Michaelides, Michel, Lambert, Michele P, Makris, Mike, De Vries, Minka, Mahdi-Rogers, Mohamed, Saleem, Moin, Thomas, Moira, Holder, Muriel, Eyries, Melanie, Clements-Brod, Naomi, Canham, Natalie, Dormand, Natalie, Van Zuydam, Natalie, Kingston, Nathalie, Ghali, Neeti, Cooper, Nichola, Morrell, Nicholas W, Yeatman, Nigel, Roy, Noemi, Shamardina, Olga, Alavijeh, Omid S, Gresele, Paolo, Nurden, Paquita, Chinnery, Patrick, Deegan, Patrick, Yong, Patrick, Yu-Wai-Man, Patrick, Corris, Paul A, Calleja, Paul, Gissen, Paul, Bolton-Maggs, Paula, Rayner-Matthews, Paula, Ghataorhe, Pavandeep K, Gordins, Pavel, Stein, Penelope, Collins, Peter, Dixon, Peter, Kelleher, Peter, Ancliff, Phil, Yu, Ping, Tait, R Campbell, Linger, Rachel, Doffinger, Rainer, Machado, Rajiv, Kazmi, Rashid, Sargur, Ravishankar, Favier, Remi, Tan, Rhea, Liesner, Ri, Antrobus, Richard, Sandford, Richard, Scott, Richard, Trembath, Richard, Horvath, Rita, Hadden, Rob, MackenzieRoss, Rob V, Henderson, Robert, MacLaren, Robert, James, Roger, Ghurye, Rohit, DaCosta, Rosa, Hague, Rosie, Mapeta, Rutendo, Armstrong, Ruth, Noorani, Sadia, Murng, Sai, Santra, Saikat, Tuna, Salih, Johnson, Sally, Chong, Sam, Lear, Sara, Walker, Sara, Goddard, Sarah, Mangles, Sarah, Westbury, Sarah, Mehta, Sarju, Hackett, Scott, Nejentsev, Sergey, Moledina, Shahin, Bibi, Shahnaz, Meehan, Sharon, Othman, Shokri, Revel-Vilk, Shoshana, Holden, Simon, McGowan, Simon, Staines, Simon, Savic, Sinisa, Burns, Siobhan, Grigoriadou, Sofia, Papadia, Sofia, Ashford, Sofie, Schulman, Sol, Ali, Sonia, Park, Soo-Mi, Davies, Sophie, Stock, Sophie, Ali, Souad, Deevi, Sri VV, Graf, Stefan, Ghio, Stefano, Wort, Stephen J, Jolles, Stephen, Austin, Steve, Welch, Steve, Meacham, Stuart, Rankin, Stuart, Walker, Suellen, Seneviratne, Suranjith, Holder, Susan, Sivapalaratnam, Suthesh, Richardson, Sylvia, Kuijpers, Taco, Kuijpers, Taco W, Bariana, Tadbir K, Bakchoul, Tamam, Everington, Tamara, Renton, Tara, Young, Tim, Aitman, Timothy, Warner, Timothy Q, Vale, Tom, Hammerton, Tracey, Pollock, Val, Matser, Vera, Cookson, Victoria, Clowes, Virginia, Qasim, Waseem, Wei, Wei, Erber, Wendy N, Ouwehand, Willem H, Astle, William, Egner, William, Turek, Wojciech, Henskens, Yvonne, Tan, Yvonne, and Dis, NIHR BioResource-Rare
Published: 2018

26. Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data

Author: Farmery, James H. R., Smith, Mike L., Huissoon, Aarnoud, Furnell, Abigail, Mead, Adam, Levine, Adam P., Manzur, Adnan, Thrasher, Adrian, Greenhalgh, Alan, Parker, Alasdair, Sanchis-Juan, Alba, Richter, Alex, Gardham, Alice, Lawrie, Allan, Sohal, Aman, Creaser-Myers, Amanda, Frary, Amy, Greinacher, Andreas, Themistocleous, Andreas, Peacock, Andrew J., Marshall, Andrew, Mumford, Andrew, Rice, Andrew, Webster, Andrew, Brady, Angie, Koziell, Ania, Manson, Ania, Chandra, Anita, Hensiek, Anke, Veld, Anna Huis In'T., Maw, Anna, Kelly, Anne M., Moore, Anthony, Vonk Noordegraaf, Anton, Attwood, Antony, Herwadkar, Archana, Ghofrani, Ardi, Houweling, Arjan C., Girerd, Barbara, Furie, Bruce, Treacy, Carmen M., Millar, Carolyn M., Sewell, Carrock, Roughley, Catherine, Titterton, Catherine, Williamson, Catherine, Hadinnapola, Charaka, Deshpande, Charu, Toh, Cheng-Hock, Bacchelli, Chiara, Patch, Chris, Geet, Chris Van, Babbs, Christian, Bryson, Christine, Penkett, Christopher J., Rhodes, Christopher J., Watt, Christopher, Bethune, Claire, Booth, Claire, Lentaigne, Claire, McJannet, Coleen, Church, Colin, French, Courtney, Samarghitean, Crina, Halmagyi, Csaba, Gale, Daniel, Greene, Daniel, Hart, Daniel, Allsup, David, Bennett, David, Edgar, David, Kiely, David G., Gosal, David, Perry, David J., Keeling, David, Montani, David, Shipley, Debbie, Whitehorn, Deborah, Fletcher, Debra, Krishnakumar, Deepa, Grozeva, Detelina, Kumararatne, Dinakantha, Thompson, Dorothy, Josifova, Dragana, Maher, Eamonn, Wong, Edwin K. S., Murphy, Elaine, Dewhurst, Eleanor, Louka, Eleni, Rosser, Elisabeth, Chalmers, Elizabeth, Colby, Elizabeth, Drewe, Elizabeth, McDermott, Elizabeth, Thomas, Ellen, Staples, Emily, Clement, Emma, Matthews, Emma, Wakeling, Emma, Oksenhendler, Eric, Turro, Ernest, Reid, Evan, Wassmer, Evangeline, Raymond, F. Lucy, Hu, Fengyuan, Kennedy, Fiona, Soubrier, Florent, Flinter, Frances, Kovacs, Gabor, Polwarth, Gary, Ambegaonkar, Gautum, Arno, Gavin, Hudson, Gavin, Woods, Geoff, Coghlan, Gerry, Hayman, Grant, Arumugakani, Gururaj, Schotte, Gwen, Cook, H. Terry, Alachkar, Hana, Lango Allen, Hana, Lango-Allen, Hana, Stark, Hannah, Stauss, Hans, Schulze, Harald, Boggard, Harm J., Baxendale, Helen, Dolling, Helen, Firth, Helen, Gall, Henning, Watson, Henry, Longhurst, Hilary, Markus, Hugh S., Watkins, Hugh, Simeoni, Ilenia, Emmerson, Ingrid, Roberts, Irene, Quinti, Isabella, Wanjiku, Ivy, Gibbs, J. Simon R., Thaventhiran, James, Whitworth, James, Hurst, Jane, Collins, Janine, Suntharalingam, Jay, Payne, Jeanette, Thachil, Jecko, Martin, Jennifer M., Carmichael, Jenny, Maimaris, Jesmeen, Paterson, Joan, Pepke-Zaba, Joanna, Heemskerk, Johan W. M., Gebhart, Johanna, Davis, John, Pasi, John, Bradley, John R., Wharton, John, Stephens, Jonathan, Rankin, Julia, Anderson, Julie, Vogt, Julie, von Ziegenweldt, Julie, Rehnstrom, Karola, Megy, Karyn, Talks, Kate, Peerlinck, Kathelijne, Yates, Katherine, Freson, Kathleen, Stirrups, Kathleen, Gomez, Keith, Smith, Kenneth G. C., Rue-Albrecht, Kevin, Gilmour, Kimberley, Masati, Larahmie, Scelsi, Laura, Southgate, Laura, Ranganathan, Lavanya, Ginsberg, Lionel, Devlin, Lisa, Willcocks, Lisa, Ormondroyd, Liz, Lorenzo, Lorena, Harper, Lorraine, Allen, Louise, Daugherty, Louise, Chitre, Manali, Kurian, Manju, Humbert, Marc, Tischkowitz, Marc, Bitner-Glindzicz, Maria, Erwood, Marie, Scully, Marie, Veltman, Marijke, Caulfield, Mark, Layton, Mark, McCarthy, Mark, Ponsford, Mark, Toshner, Mark, Bleda, Marta, Wilkins, Martin, Mathias, Mary, Reilly, Mary, Afzal, Maryam, Brown, Matthew, Rondina, Matthew, Stubbs, Matthew, Haimel, Matthias, Lees, Melissa, Laffan, Michael A., Browning, Michael, Gattens, Michael, Richards, Michael, Michaelides, Michel, Lambert, Michele P., Makris, Mike, de Vries, Minka, Mahdi-Rogers, Mohamed, Saleem, Moin, Thomas, Moira, Holder, Muriel, Eyries, M. lanie, Clements-Brod, Naomi, Canham, Natalie, Dormand, Natalie, Zuydam, Natalie Van, Kingston, Nathalie, Ghali, Neeti, Cooper, Nichola, Morrell, Nicholas W., Yeatman, Nigel, Roy, Noémi, Shamardina, Olga, Alavijeh, Omid S., Gresele, Paolo, Nurden, Paquita, Chinnery, Patrick, Deegan, Patrick, Yong, Patrick, Man, Patrick Yu Wai, Corris, Paul A., Calleja, Paul, Gissen, Paul, Bolton-Maggs, Paula, Rayner-Matthews, Paula, Ghataorhe, Pavandeep K., Gordins, Pavel, Stein, Penelope, Collins, Peter, Dixon, Peter, Kelleher, Peter, Ancliff, Phil, Yu, Ping, Tait, R. Campbell, Linger, Rachel, Doffinger, Rainer, Machado, Rajiv, Kazmi, Rashid, Sargur, Ravishankar, Favier, Remi, Tan, Rhea, Liesner, Ri, Antrobus, Richard, Sandford, Richard, Scott, Richard, Trembath, Richard, Horvath, Rita, Hadden, Rob, Mackenzieross, Rob V., Henderson, Robert, MacLaren, Robert, James, Roger, Ghurye, Rohit, Dacosta, Rosa, Hague, Rosie, Mapeta, Rutendo, Armstrong, Ruth, Noorani, Sadia, Murng, Sai, Santra, Saikat, Tuna, Salih, Johnson, Sally, Chong, Sam, Lear, Sara, Walker, Sara, Goddard, Sarah, Mangles, Sarah, Westbury, Sarah, Mehta, Sarju, Hackett, Scott, Nejentsev, Sergey, Moledina, Shahin, Bibi, Shahnaz, Meehan, Sharon, Othman, Shokri, Revel-Vilk, Shoshana, Holden, Simon, McGowan, Simon, Staines, Simon, Savic, Sinisa, Burns, Siobhan, Grigoriadou, Sofia, Papadia, Sofia, Ashford, Sofie, Schulman, Sol, Ali, Sonia, Park, Soo-Mi, Davies, Sophie, Stock, Sophie, Ali, Souad, Deevi, Sri V. V., Gräf, Stefan, Ghio, Stefano, Wort, Stephen J., Jolles, Stephen, Austin, Steve, Welch, Steve, Meacham, Stuart, Rankin, Stuart, Walker, Suellen, Seneviratne, Suranjith, Holder, Susan, Sivapalaratnam, Suthesh, Richardson, Sylvia, Kuijpers, Taco, Kuijpers, Taco W., Bariana, Tadbir K., Bakchoul, Tamam, Everington, Tamara, Renton, Tara, Young, Tim, Aitman, Timothy, Warner, Timothy Q., Vale, Tom, Hammerton, Tracey, Pollock, Val, Matser, Vera, Cookson, Victoria, Clowes, Virginia, Qasim, Waseem, Wei, Wei, Erber, Wendy N., Ouwehand, Willem H., Astle, William, Egner, William, Turek, Wojciech, Henskens, Yvonne, Tan, Yvonne, Lynch, Andy G., Other departments, ARD - Amsterdam Reproduction and Development, Paediatric Infectious Diseases / Rheumatology / Immunology, Peerlinck, Kathelijne, Freson, Kathleen, University of St Andrews. Statistics, University of St Andrews. School of Medicine, University of St Andrews. Population and Behavioural Science Division, University of St Andrews. Cellular Medicine Division, Rue-Albrecht, K, VU University medical center, ACS - Pulmonary hypertension & thrombosis, Pulmonary medicine, APH - Quality of Care, Amsterdam Reproduction & Development (AR&D), Human genetics, ACS - Atherosclerosis & ischemic syndromes, Molecular cell biology and Immunology, Pediatric surgery, APH - Aging & Later Life, Lynch, Andy G [0000-0002-7876-7338], and Apollo - University of Cambridge Repository
Subjects: Telomerase, Carcinoma, Hepatocellular, Genotype, Science, QH301 Biology, Induced Pluripotent Stem Cells, Primary Cell Culture, Sequencing data, Gene Expression, Computational biology, Biology, Article, RC0254, 03 medical and health sciences, QH301, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Humans, 030304 developmental biology, Whole genome sequencing, 0303 health sciences, Ploidies, Multidisciplinary, Whole Genome Sequencing, Telomere biology, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Liver Neoplasms, Telomere Homeostasis, Mesenchymal Stem Cells, DAS, Telomere, Publisher Correction, T Technology, Cancer data, 030220 oncology & carcinogenesis, Medicine, Ploidy, Algorithms
Abstract: Funding: Cancer Research UK Programme Grant to Simon Tavaré (C14303/A17197) (JHRF, AGL, MLS); European Commission through the Horizon 2020 project SOUND (Grant Agreement no. 633974) (AGL). Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype. Publisher PDF
Published: 2018

27. Erratum to: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data (Scientific Reports, (2018), 8, 1, (1300), 10.1038/s41598-017-14403-y)

Author: Farmery, James H. R., Smith, Mike L., Huissoon, Aarnoud, Furnell, Abigail, Mead, Adam, Levine, Adam P., Manzur, Adnan, Thrasher, Adrian, Greenhalgh, Alan, Parker, Alasdair, Sanchis-Juan, Alba, Richter, Alex, Gardham, Alice, Lawrie, Allan, Sohal, Aman, Creaser-Myers, Amanda, Frary, Amy, Greinacher, Andreas, Themistocleous, Andreas, Peacock, Andrew J., Marshall, Andrew, Mumford, Andrew, Rice, Andrew, Webster, Andrew, Brady, Angie, Koziell, Ania, Manson, Ania, Chandra, Anita, Hensiek, Anke, Veld, Anna Huis in’t, Maw, Anna, Kelly, Anne M., Moore, Anthony, Vonk Noordegraaf, Anton, Attwood, Antony, Herwadkar, Archana, Ghofrani, Ardi, Houweling, Arjan C., Girerd, Barbara, Furie, Bruce, Treacy, Carmen M., Millar, Carolyn M., Sewell, Carrock, Roughley, Catherine, Titterton, Catherine, Williamson, Catherine, Hadinnapola, Charaka, Deshpande, Charu, Toh, Cheng-Hock, Bacchelli, Chiara, Patch, Chris, Geet, Chris Van, Babbs, Christian, Bryson, Christine, Penkett, Christopher J., Rhodes, Christopher J., Watt, Christopher, Bethune, Claire, Booth, Claire, Lentaigne, Claire, Mcjannet, Coleen, Church, Colin, French, Courtney, Samarghitean, Crina, Halmagyi, Csaba, Gale, Daniel, Greene, Daniel, Hart, Daniel, Allsup, David, Bennett, David, Edgar, David, Kiely, David G., Gosal, David, Perry, David J., Keeling, David, Montani, David, Shipley, Debbie, Whitehorn, Deborah, Fletcher, Debra, Krishnakumar, Deepa, Grozeva, Detelina, Kumararatne, Dinakantha, Thompson, Dorothy, Josifova, Dragana, Maher, Eamonn, Wong, Edwin K. S., Murphy, Elaine, Dewhurst, Eleanor, Louka, Eleni, Rosser, Elisabeth, Chalmers, Elizabeth, Colby, Elizabeth, Drewe, Elizabeth, Mcdermott, Elizabeth, Thomas, Ellen, Staples, Emily, Clement, Emma, Matthews, Emma, Wakeling, Emma, Oksenhendler, Eric, Turro, Ernest, Reid, Evan, Wassmer, Evangeline, Raymond, F. Lucy, Fengyuan, Hu, Kennedy, Fiona, Soubrier, Florent, Flinter, Frances, Kovacs, Gabor, Polwarth, Gary, Ambegaonkar, Gautum, Arno, Gavin, Hudson, Gavin, Woods, Geoff, Coghlan, Gerry, Hayman, Grant, Arumugakani, Gururaj, Schotte, Gwen, Cook, H. Terry, Alachkar, Hana, Lango Allen, Hana, Lango-Allen, Hana, Stark, Hannah, Stauss, Hans, Schulze, Harald, Boggard, Harm J., Baxendale, Helen, Dolling, Helen, Firth, Helen, Gall, Henning, Watson, Henry, Longhurst, Hilary, Markus, Hugh S., Watkins, Hugh, Simeoni, Ilenia, Emmerson, Ingrid, Roberts, Irene, Quinti, Isabella, Wanjiku, Ivy, Gibbs, J. Simon R., Thaventhiran, James, Whitworth, James, Hurst, Jane, Collins, Janine, Suntharalingam, Jay, Payne, Jeanette, Thachil, Jecko, Martin, Jennifer M., Martin, Jennifer, Carmichael, Jenny, Maimaris, Jesmeen, Paterson, Joan, Pepke-Zaba, Joanna, Heemskerk, Johan W. M., Gebhart, Johanna, Davis, John, Pasi, John, Bradley, John R., Wharton, John, Stephens, Jonathan, Rankin, Julia, Anderson, Julie, Vogt, Julie, von Ziegenweldt, Julie, Rehnstrom, Karola, Megy, Karyn, Talks, Kate, Peerlinck, Kathelijne, Yates, Katherine, Freson, Kathleen, Stirrups, Kathleen, Gomez, Keith, Smith, Kenneth G. C., Carss, Keren, Rue-Albrecht, Kevin, Gilmour, Kimberley, Masati, Larahmie, Scelsi, Laura, Southgate, Laura, Ranganathan, Lavanya, Ginsberg, Lionel, Devlin, Lisa, Willcocks, Lisa, Ormondroyd, Liz, Lorenzo, Lorena, Harper, Lorraine, Allen, Louise, Daugherty, Louise, Chitre, Manali, Kurian, Manju, Humbert, Marc, Tischkowitz, Marc, Bitner-Glindzicz, Maria, Erwood, Marie, Scully, Marie, Veltman, Marijke, Caulfield, Mark, Layton, Mark, Mccarthy, Mark, Ponsford, Mark, Toshner, Mark, Bleda, Marta, Wilkins, Martin, Mathias, Mary, Reilly, Mary, Afzal, Maryam, Brown, Matthew, Rondina, Matthew, Stubbs, Matthew, Haimel, Matthias, Lees, Melissa, Laffan, Michael A., Browning, Michael, Gattens, Michael, Richards, Michael, Michaelides, Michel, Lambert, Michele P., Makris, Mike, De Vries, Minka, Mahdi-Rogers, Mohamed, Saleem, Moin, Thomas, Moira, Holder, Muriel, Eyries, Mélanie, Clements-Brod, Naomi, Canham, Natalie, Dormand, Natalie, Zuydam, Natalie Van, Kingston, Nathalie, Ghali, Neeti, Cooper, Nichola, Morrell, Nicholas W., Yeatman, Nigel, Roy, Noémi, Shamardina, Olga, Alavijeh, Omid S., Gresele, Paolo, Nurden, Paquita, Chinnery, Patrick, Deegan, Patrick, Yong, Patrick, Yu-Wai-Man, Patrick, Corris, Paul A., Calleja, Paul, Gissen, Paul, Bolton-Maggs, Paula, Rayner-Matthews, Paula, Ghataorhe, Pavandeep K., Gordins, Pavel, Stein, Penelope, Collins, Peter, Dixon, Peter, Kelleher, Peter, Ancliff, Phil, Ping, Yu, Tait, R. Campbell, Linger, Rachel, Doffinger, Rainer, Machado, Rajiv, Kazmi, Rashid, Sargur, Ravishankar, Favier, Remi, Tan, Rhea, Liesner, Ri, Antrobus, Richard, Sandford, Richard, Scott, Richard, Trembath, Richard, Horvath, Rita, Hadden, Rob, Mackenzieross, Rob V., Henderson, Robert, Maclaren, Robert, James, Roger, Ghurye, Rohit, Dacosta, Rosa, Hague, Rosie, Mapeta, Rutendo, Armstrong, Ruth, Noorani, Sadia, Murng, Sai, Santra, Saikat, Tuna, Salih, Johnson, Sally, Chong, Sam, Lear, Sara, Walker, Sara, Goddard, Sarah, Mangles, Sarah, Westbury, Sarah, Mehta, Sarju, Hackett, Scott, Nejentsev, Sergey, Moledina, Shahin, Bibi, Shahnaz, Meehan, Sharon, Othman, Shokri, Revel-Vilk, Shoshana, Holden, Simon, Mcgowan, Simon, Staines, Simon, Savic, Sinisa, Burns, Siobhan, Grigoriadou, Sofia, Papadia, Sofia, Ashford, Sofie, Schulman, Sol, Ali, Sonia, Park, Soo-Mi, Davies, Sophie, Stock, Sophie, Ali, Souad, Deevi, Sri V. V., Gräf, Stefan, Ghio, Stefano, Wort, Stephen J., Jolles, Stephen, Austin, Steve, Welch, Steve, Meacham, Stuart, Rankin, Stuart, Walker, Suellen, Seneviratne, Suranjith, Holder, Susan, Sivapalaratnam, Suthesh, Richardson, Sylvia, Kuijpers, Taco, Kuijpers, Taco W., Bariana, Tadbir K., Bakchoul, Tamam, Everington, Tamara, Renton, Tara, Young, Tim, Aitman, Timothy, Warner, Timothy Q., Vale, Tom, Hammerton, Tracey, Pollock, Val, Matser, Vera, Cookson, Victoria, Clowes, Virginia, Qasim, Waseem, Wei, Wei, Erber, Wendy N., Ouwehand, Willem H., Astle, William, Egner, William, Turek, Wojciech, Henskens, Yvonne, Tan, Yvonne, and Lynch, Andy G.
Subjects: Multidisciplinary
Published: 2018

28. Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia

Author: Gorman, Kathleen M., primary, Meyer, Esther, additional, Grozeva, Detelina, additional, Spinelli, Egidio, additional, McTague, Amy, additional, Sanchis-Juan, Alba, additional, Carss, Keren J., additional, Bryant, Emily, additional, Reich, Adi, additional, Schneider, Amy L., additional, Pressler, Ronit M., additional, Simpson, Michael A., additional, Debelle, Geoff D., additional, Wassmer, Evangeline, additional, Morton, Jenny, additional, Sieciechowicz, Diana, additional, Jan-Kamsteeg, Eric, additional, Paciorkowski, Alex R., additional, King, Mary D., additional, Cross, J. Helen, additional, Poduri, Annapurna, additional, Mefford, Heather C., additional, Scheffer, Ingrid E., additional, Haack, Tobias B., additional, McCullagh, Gary, additional, Millichap, John J., additional, Carvill, Gemma L., additional, Clayton-Smith, Jill, additional, Maher, Eamonn R., additional, Raymond, F. Lucy, additional, Kurian, Manju A., additional, McRae, Jeremy F., additional, Clayton, Stephen, additional, Fitzgerald, Tomas W., additional, Kaplanis, Joanna, additional, Prigmore, Elena, additional, Rajan, Diana, additional, Sifrim, Alejandro, additional, Aitken, Stuart, additional, Akawi, Nadia, additional, Alvi, Mohsan, additional, Ambridge, Kirsty, additional, Barrett, Daniel M., additional, Bayzetinova, Tanya, additional, Jones, Philip, additional, Jones, Wendy D., additional, King, Daniel, additional, Krishnappa, Netravathi, additional, Mason, Laura E., additional, Singh, Tarjinder, additional, Tivey, Adrian R., additional, Ahmed, Munaza, additional, Anjum, Uruj, additional, Archer, Hayley, additional, Armstrong, Ruth, additional, Awada, Jana, additional, Balasubramanian, Meena, additional, Banka, Siddharth, additional, Baralle, Diana, additional, Barnicoat, Angela, additional, Batstone, Paul, additional, Baty, David, additional, Bennett, Chris, additional, Berg, Jonathan, additional, Bernhard, Birgitta, additional, Bevan, A. Paul, additional, Bitner-Glindzicz, Maria, additional, Blair, Edward, additional, Blyth, Moira, additional, Bohanna, David, additional, Bourdon, Louise, additional, Bourn, David, additional, Bradley, Lisa, additional, Brady, Angela, additional, Brent, Simon, additional, Brewer, Carole, additional, Brunstrom, Kate, additional, Bunyan, David J., additional, Burn, John, additional, Canham, Natalie, additional, Castle, Bruce, additional, Chandler, Kate, additional, Chatzimichali, Elena, additional, Cilliers, Deirdre, additional, Clarke, Angus, additional, Clasper, Susan, additional, Clowes, Virginia, additional, Coates, Andrea, additional, Cole, Trevor, additional, Colgiu, Irina, additional, Collins, Amanda, additional, Collinson, Morag N., additional, Connell, Fiona, additional, Cooper, Nicola, additional, Cox, Helen, additional, Cresswell, Lara, additional, Cross, Gareth, additional, Crow, Yanick, additional, D’Alessandro, Mariella, additional, Dabir, Tabib, additional, Davidson, Rosemarie, additional, Davies, Sally, additional, de Vries, Dylan, additional, Dean, John, additional, Deshpande, Charu, additional, Devlin, Gemma, additional, Dixit, Abhijit, additional, Dobbie, Angus, additional, Donaldson, Alan, additional, Donnai, Dian, additional, Donnelly, Deirdre, additional, Donnelly, Carina, additional, Douglas, Angela, additional, Douzgou, Sofia, additional, Duncan, Alexis, additional, Eason, Jacqueline, additional, Ellard, Sian, additional, Ellis, Ian, additional, Elmslie, Frances, additional, Evans, Karenza, additional, Everest, Sarah, additional, Fendick, Tina, additional, Fisher, Richard, additional, Flinter, Frances, additional, Foulds, Nicola, additional, Fry, Andrew, additional, Fryer, Alan, additional, Gardiner, Carol, additional, Gaunt, Lorraine, additional, Ghali, Neeti, additional, Gibbons, Richard, additional, Gill, Harinder, additional, Goodship, Judith, additional, Goudie, David, additional, Gray, Emma, additional, Green, Andrew, additional, Greene, Philip, additional, Greenhalgh, Lynn, additional, Gribble, Susan, additional, Harrison, Rachel, additional, Harrison, Lucy, additional, Harrison, Victoria, additional, Hawkins, Rose, additional, He, Liu, additional, Hellens, Stephen, additional, Henderson, Alex, additional, Hewitt, Sarah, additional, Hildyard, Lucy, additional, Hobson, Emma, additional, Holden, Simon, additional, Holder, Muriel, additional, Holder, Susan, additional, Hollingsworth, Georgina, additional, Homfray, Tessa, additional, Humphreys, Mervyn, additional, Hurst, Jane, additional, Hutton, Ben, additional, Ingram, Stuart, additional, Irving, Melita, additional, Islam, Lily, additional, Jackson, Andrew, additional, Jarvis, Joanna, additional, Jenkins, Lucy, additional, Johnson, Diana, additional, Jones, Elizabeth, additional, Josifova, Dragana, additional, Joss, Shelagh, additional, Kaemba, Beckie, additional, Kazembe, Sandra, additional, Kelsell, Rosemary, additional, Kerr, Bronwyn, additional, Kingston, Helen, additional, Kini, Usha, additional, Kinning, Esther, additional, Kirby, Gail, additional, Kirk, Claire, additional, Kivuva, Emma, additional, Kraus, Alison, additional, Kumar, Dhavendra, additional, Kumar, V. K. Ajith, additional, Lachlan, Katherine, additional, Lam, Wayne, additional, Lampe, Anne, additional, Langman, Caroline, additional, Lees, Melissa, additional, Lim, Derek, additional, Longman, Cheryl, additional, Lowther, Gordon, additional, Lynch, Sally A., additional, Magee, Alex, additional, Maher, Eddy, additional, Male, Alison, additional, Mansour, Sahar, additional, Marks, Karen, additional, Martin, Katherine, additional, Maye, Una, additional, McCann, Emma, additional, McConnell, Vivienne, additional, McEntagart, Meriel, additional, McGowan, Ruth, additional, McKay, Kirsten, additional, McKee, Shane, additional, McMullan, Dominic J., additional, McNerlan, Susan, additional, McWilliam, Catherine, additional, Mehta, Sarju, additional, Metcalfe, Kay, additional, Middleton, Anna, additional, Miedzybrodzka, Zosia, additional, Miles, Emma, additional, Mohammed, Shehla, additional, Montgomery, Tara, additional, Moore, David, additional, Morgan, Sian, additional, Mugalaasi, Hood, additional, Murday, Victoria, additional, Murphy, Helen, additional, Naik, Swati, additional, Nemeth, Andrea, additional, Nevitt, Louise, additional, Newbury-Ecob, Ruth, additional, Norman, Andrew, additional, O’Shea, Rosie, additional, Ogilvie, Caroline, additional, Ong, Kai-Ren, additional, Park, Soo-Mi, additional, Parker, Michael J., additional, Patel, Chirag, additional, Paterson, Joan, additional, Payne, Stewart, additional, Perrett, Daniel, additional, Phipps, Julie, additional, Pilz, Daniela T., additional, Pollard, Martin, additional, Pottinger, Caroline, additional, Poulton, Joanna, additional, Pratt, Norman, additional, Prescott, Katrina, additional, Price, Sue, additional, Pridham, Abigail, additional, Procter, Annie, additional, Purnell, Hellen, additional, Quarrell, Oliver, additional, Ragge, Nicola, additional, Rahbari, Raheleh, additional, Randall, Josh, additional, Rankin, Julia, additional, Raymond, Lucy, additional, Rice, Debbie, additional, Robert, Leema, additional, Roberts, Eileen, additional, Roberts, Jonathan, additional, Roberts, Paul, additional, Roberts, Gillian, additional, Ross, Alison, additional, Rosser, Elisabeth, additional, Saggar, Anand, additional, Samant, Shalaka, additional, Sampson, Julian, additional, Sandford, Richard, additional, Sarkar, Ajoy, additional, Schweiger, Susann, additional, Scott, Richard, additional, Scurr, Ingrid, additional, Selby, Ann, additional, Seller, Anneke, additional, Sequeira, Cheryl, additional, Shannon, Nora, additional, Sharif, Saba, additional, Shaw-Smith, Charles, additional, Shearing, Emma, additional, Shears, Debbie, additional, Sheridan, Eamonn, additional, Simonic, Ingrid, additional, Singzon, Roldan, additional, Skitt, Zara, additional, Smith, Audrey, additional, Smith, Kath, additional, Smithson, Sarah, additional, Sneddon, Linda, additional, Splitt, Miranda, additional, Squires, Miranda, additional, Stewart, Fiona, additional, Stewart, Helen, additional, Straub, Volker, additional, Suri, Mohnish, additional, Sutton, Vivienne, additional, Swaminathan, Ganesh Jawahar, additional, Sweeney, Elizabeth, additional, Tatton-Brown, Kate, additional, Taylor, Cat, additional, Taylor, Rohan, additional, Tein, Mark, additional, Temple, I. Karen, additional, Thomson, Jenny, additional, Tischkowitz, Marc, additional, Tomkins, Susan, additional, Torokwa, Audrey, additional, Treacy, Becky, additional, Turner, Claire, additional, Turnpenny, Peter, additional, Tysoe, Carolyn, additional, Vandersteen, Anthony, additional, Varghese, Vinod, additional, Vasudevan, Pradeep, additional, Vijayarangakannan, Parthiban, additional, Vogt, Julie, additional, Wakeling, Emma, additional, Wallwark, Sarah, additional, Waters, Jonathon, additional, Weber, Astrid, additional, Wellesley, Diana, additional, Whiteford, Margo, additional, Widaa, Sara, additional, Wilcox, Sarah, additional, Wilkinson, Emily, additional, Williams, Denise, additional, Williams, Nicola, additional, Wilson, Louise, additional, Woods, Geoff, additional, Wragg, Christopher, additional, Wright, Michael, additional, Yates, Laura, additional, Yau, Michael, additional, Nellåker, Chris, additional, Parker, Michael, additional, Firth, Helen V., additional, Wright, Caroline F., additional, FitzPatrick, David R., additional, Barrett, Jeffrey C., additional, Hurles, Matthew E., additional, Al Turki, Saeed, additional, Anderson, Carl, additional, Anney, Richard, additional, Antony, Dinu, additional, Artigas, Maria Soler, additional, Ayub, Muhammad, additional, Balasubramaniam, Senduran, additional, Barroso, Inês, additional, Beales, Phil, additional, Bentham, Jamie, additional, Bhattacharya, Shoumo, additional, Birney, Ewan, additional, Blackwood, Douglas, additional, Bobrow, Martin, additional, Bochukova, Elena, additional, Bolton, Patrick, additional, Bounds, Rebecca, additional, Boustred, Chris, additional, Breen, Gerome, additional, Calissano, Mattia, additional, Carss, Keren, additional, Chatterjee, Krishna, additional, Chen, Lu, additional, Ciampi, Antonio, additional, Cirak, Sebhattin, additional, Clapham, Peter, additional, Clement, Gail, additional, Coates, Guy, additional, Collier, David, additional, Cosgrove, Catherine, additional, Cox, Tony, additional, Craddock, Nick, additional, Crooks, Lucy, additional, Curran, Sarah, additional, Curtis, David, additional, Daly, Allan, additional, Day-Williams, Aaron, additional, Day, Ian N.M., additional, Down, Thomas, additional, Du, Yuanping, additional, Dunham, Ian, additional, Edkins, Sarah, additional, Ellis, Peter, additional, Evans, David, additional, Faroogi, Sadaf, additional, Fatemifar, Ghazaleh, additional, Fitzpatrick, David R., additional, Flicek, Paul, additional, Flyod, James, additional, Foley, A. Reghan, additional, Franklin, Christopher S., additional, Futema, Marta, additional, Gallagher, Louise, additional, Geihs, Matthias, additional, Geschwind, Daniel, additional, Griffin, Heather, additional, Guo, Xueqin, additional, Guo, Xiaosen, additional, Gurling, Hugh, additional, Hart, Deborah, additional, Hendricks, Audrey, additional, Holmans, Peter, additional, Howie, Bryan, additional, Huang, Liren, additional, Hubbard, Tim, additional, Humphries, Steve E., additional, Hysi, Pirro, additional, Jackson, David K., additional, Jamshidi, Yalda, additional, Jing, Tian, additional, Joyce, Chris, additional, Kaye, Jane, additional, Keane, Thomas, additional, Keogh, Julia, additional, Kemp, John, additional, Kennedy, Karen, additional, Kolb-Kokocinski, Anja, additional, Lachance, Genevieve, additional, Langford, Cordelia, additional, Lawson, Daniel, additional, Lee, Irene, additional, Lek, Monkol, additional, Liang, Jieqin, additional, Lin, Hong, additional, Li, Rui, additional, Li, Yingrui, additional, Liu, Ryan, additional, Lönnqvist, Jouko, additional, Lopes, Margarida, additional, Iotchkova, Valentina, additional, MacArthur, Daniel, additional, Marchini, Jonathan, additional, Maslen, John, additional, Massimo, Mangino, additional, Mathieson, Iain, additional, Marenne, Gaëlle, additional, McGuffin, Peter, additional, McIntosh, Andrew, additional, McKechanie, Andrew G., additional, McQuillin, Andrew, additional, Metrustry, Sarah, additional, Mitchison, Hannah, additional, Moayyeri, Alireza, additional, Morris, James, additional, Muntoni, Francesco, additional, Northstone, Kate, additional, O'Donnovan, Michael, additional, Onoufriadis, Alexandros, additional, O'Rahilly, Stephen, additional, Oualkacha, Karim, additional, Owen, Michael J., additional, Palotie, Aarno, additional, Panoutsopoulou, Kalliope, additional, Parker, Victoria, additional, Parr, Jeremy R., additional, Paternoster, Lavinia, additional, Paunio, Tiina, additional, Payne, Felicity, additional, Pietilainen, Olli, additional, Plagnol, Vincent, additional, Quaye, Lydia, additional, Quail, Michael A., additional, Rehnström, Karola, additional, Ring, Susan, additional, Ritchie, Graham R.S., additional, Roberts, Nicola, additional, Savage, David B., additional, Scambler, Peter, additional, Schiffels, Stephen, additional, Schmidts, Miriam, additional, Schoenmakers, Nadia, additional, Semple, Robert K., additional, Serra, Eva, additional, Sharp, Sally I., additional, Shin, So-Youn, additional, Skuse, David, additional, Small, Kerrin, additional, Southam, Lorraine, additional, Spasic-Boskovic, Olivera, additional, St Clair, David, additional, Stalker, Jim, additional, Stevens, Elizabeth, additional, St Pourcian, Beate, additional, Sun, Jianping, additional, Suvisaari, Jaana, additional, Tachmazidou, Ionna, additional, Tobin, Martin D., additional, Valdes, Ana, additional, Van Kogelenberg, Margriet, additional, Visscher, Peter M., additional, Wain, Louise V., additional, Walters, James T.R., additional, Wang, Guangbiao, additional, Wang, Jun, additional, Wang, Yu, additional, Ward, Kirsten, additional, Wheeler, Elanor, additional, Whyte, Tamieka, additional, Williams, Hywel, additional, Williamson, Kathleen A., additional, Wilson, Crispian, additional, Wong, Kim, additional, Xu, ChangJiang, additional, Yang, Jian, additional, Zhang, Fend, additional, Zhang, Pingbo, additional, Aitman, Timothy, additional, Alachkar, Hana, additional, Ali, Sonia, additional, Allen, Louise, additional, Allsup, David, additional, Ambegaonkar, Gautum, additional, Anderson, Julie, additional, Antrobus, Richard, additional, Arno, Gavin, additional, Arumugakani, Gururaj, additional, Ashford, Sofie, additional, Astle, William, additional, Attwood, Antony, additional, Austin, Steve, additional, Bacchelli, Chiara, additional, Bakchoul, Tamam, additional, Bariana, Tadbir K., additional, Baxendale, Helen, additional, Bennett, David, additional, Bethune, Claire, additional, Bibi, Shahnaz, additional, Bleda, Marta, additional, Boggard, Harm, additional, Bolton-Maggs, Paula, additional, Booth, Claire, additional, Bradley, John R., additional, Brady, Angie, additional, Brown, Matthew, additional, Browning, Michael, additional, Bryson, Christine, additional, Burns, Siobhan, additional, Calleja, Paul, additional, Carmichael, Jenny, additional, Caulfield, Mark, additional, Chalmers, Elizabeth, additional, Chandra, Anita, additional, Chinnery, Patrick, additional, Chitre, Manali, additional, Church, Colin, additional, Clement, Emma, additional, Clements-Brod, Naomi, additional, Coghlan, Gerry, additional, Collins, Peter, additional, Cooper, Nichola, additional, Creaser-Myers, Amanda, additional, DaCosta, Rosa, additional, Daugherty, Louise, additional, Davies, Sophie, additional, Davis, John, additional, De Vries, Minka, additional, Deegan, Patrick, additional, Deevi, Sri V.V., additional, Devlin, Lisa, additional, Dewhurst, Eleanor, additional, Doffinger, Rainer, additional, Dormand, Natalie, additional, Drewe, Elizabeth, additional, Edgar, David, additional, Egner, William, additional, Erber, Wendy N., additional, Erwood, Marie, additional, Everington, Tamara, additional, Favier, Remi, additional, Firth, Helen, additional, Fletcher, Debra, additional, Fox, James C., additional, Frary, Amy, additional, Freson, Kathleen, additional, Furie, Bruce, additional, Furnell, Abigail, additional, Gale, Daniel, additional, Gardham, Alice, additional, Gattens, Michael, additional, Ghataorhe, Pavandeep K., additional, Ghurye, Rohit, additional, Gibbs, Simon, additional, Gilmour, Kimberley, additional, Gissen, Paul, additional, Goddard, Sarah, additional, Gomez, Keith, additional, Gordins, Pavel, additional, Gräf, Stefan, additional, Greene, Daniel, additional, Greenhalgh, Alan, additional, Greinacher, Andreas, additional, Grigoriadou, Sofia, additional, Hackett, Scott, additional, Hadinnapola, Charaka, additional, Hague, Rosie, additional, Haimel, Matthias, additional, Halmagyi, Csaba, additional, Hammerton, Tracey, additional, Hart, Daniel, additional, Hayman, Grant, additional, Heemskerk, Johan W.M., additional, Henderson, Robert, additional, Hensiek, Anke, additional, Henskens, Yvonne, additional, Herwadkar, Archana, additional, Hu, Fengyuan, additional, Huissoon, Aarnoud, additional, Humbert, Marc, additional, James, Roger, additional, Jolles, Stephen, additional, Kazmi, Rashid, additional, Keeling, David, additional, Kelleher, Peter, additional, Kelly, Anne M., additional, Kennedy, Fiona, additional, Kiely, David, additional, Kingston, Nathalie, additional, Koziell, Ania, additional, Krishnakumar, Deepa, additional, Kuijpers, Taco W., additional, Kumararatne, Dinakantha, additional, Kurian, Manju, additional, Laffan, Michael A., additional, Lambert, Michele P., additional, Allen, Hana Lango, additional, Lawrie, Allan, additional, Lear, Sara, additional, Lentaigne, Claire, additional, Liesner, Ri, additional, Linger, Rachel, additional, Longhurst, Hilary, additional, Lorenzo, Lorena, additional, Machado, Rajiv, additional, Mackenzie, Rob, additional, MacLaren, Robert, additional, Maher, Eamonn, additional, Maimaris, Jesmeen, additional, Mangles, Sarah, additional, Manson, Ania, additional, Mapeta, Rutendo, additional, Markus, Hugh S., additional, Martin, Jennifer, additional, Masati, Larahmie, additional, Mathias, Mary, additional, Matser, Vera, additional, Maw, Anna, additional, McDermott, Elizabeth, additional, McJannet, Coleen, additional, Meacham, Stuart, additional, Meehan, Sharon, additional, Megy, Karyn, additional, Michaelides, Michel, additional, Millar, Carolyn M., additional, Moledina, Shahin, additional, Moore, Anthony, additional, Morrell, Nicholas, additional, Mumford, Andrew, additional, Murng, Sai, additional, Murphy, Elaine, additional, Nejentsev, Sergey, additional, Noorani, Sadia, additional, Nurden, Paquita, additional, Oksenhendler, Eric, additional, Ouwehand, Willem H., additional, Papadia, Sofia, additional, Parker, Alasdair, additional, Pasi, John, additional, Patch, Chris, additional, Payne, Jeanette, additional, Peacock, Andrew, additional, Peerlinck, Kathelijne, additional, Penkett, Christopher J., additional, Pepke-Zaba, Joanna, additional, Perry, David J., additional, Pollock, Val, additional, Polwarth, Gary, additional, Ponsford, Mark, additional, Qasim, Waseem, additional, Quinti, Isabella, additional, Rankin, Stuart, additional, Rehnstrom, Karola, additional, Reid, Evan, additional, Rhodes, Christopher J., additional, Richards, Michael, additional, Richardson, Sylvia, additional, Richter, Alex, additional, Roberts, Irene, additional, Rondina, Matthew, additional, Roughley, Catherine, additional, Rue-Albrecht, Kevin, additional, Samarghitean, Crina, additional, Santra, Saikat, additional, Sargur, Ravishankar, additional, Savic, Sinisa, additional, Schulman, Sol, additional, Schulze, Harald, additional, Scully, Marie, additional, Seneviratne, Suranjith, additional, Sewell, Carrock, additional, Shamardina, Olga, additional, Shipley, Debbie, additional, Simeoni, Ilenia, additional, Sivapalaratnam, Suthesh, additional, Smith, Kenneth, additional, Sohal, Aman, additional, Southgate, Laura, additional, Staines, Simon, additional, Staples, Emily, additional, Stauss, Hans, additional, Stein, Penelope, additional, Stephens, Jonathan, additional, Stirrups, Kathleen, additional, Stock, Sophie, additional, Suntharalingam, Jay, additional, Tait, R. Campbell, additional, Talks, Kate, additional, Tan, Yvonne, additional, Thachil, Jecko, additional, Thaventhiran, James, additional, Thomas, Ellen, additional, Thomas, Moira, additional, Thompson, Dorothy, additional, Thrasher, Adrian, additional, Titterton, Catherine, additional, Toh, Cheng-Hock, additional, Toshner, Mark, additional, Treacy, Carmen, additional, Trembath, Richard, additional, Tuna, Salih, additional, Turek, Wojciech, additional, Turro, Ernest, additional, Van Geet, Chris, additional, Veltman, Marijke, additional, von Ziegenweldt, Julie, additional, Vonk Noordegraaf, Anton, additional, Wanjiku, Ivy, additional, Warner, Timothy Q., additional, Watkins, Hugh, additional, Webster, Andrew, additional, Welch, Steve, additional, Westbury, Sarah, additional, Wharton, John, additional, Whitehorn, Deborah, additional, Wilkins, Martin, additional, Willcocks, Lisa, additional, Williamson, Catherine, additional, Woods, Geoffrey, additional, Wort, John, additional, Yeatman, Nigel, additional, Yong, Patrick, additional, Young, Tim, additional, and Yu, Ping, additional
Published: 2019
Full Text: View/download PDF

29. Exome Sequencing Identifies Multiple Genes and Gene-Sets Contributing to Severe Childhood Obesity

Author: Marenne, Gaëlle, primary, Hendricks, Audrey, additional, Perdikari, Aliki, additional, Bounds, Rebecca, additional, Payne, Felicity, additional, Keogh, Julia M., additional, Lelliott, Christopher J., additional, Henning, Elana, additional, Pathan, Saad, additional, Ashford, Sofie, additional, Bochukova, Elena G., additional, Mistry, Vanisha, additional, Daly, Allan, additional, Hayward, Caroline, additional, Wareham, Nicholas J., additional, O'Rahilly, Stephen, additional, Langenberg, Claudia, additional, Wheeler, Eleanor, additional, Zeggini, Eleftheria, additional, Farooqi, I.Sadaf, additional, and Barroso, Ines, additional
Published: 2019
Full Text: View/download PDF

30. Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

Author: Ecker, Simone, Chen, Lu, Pancaldi, Vera, Bagger, Frederik O., Fernández, José María, Carrillo de Santa Pau, Enrique, Juan, David, Mann, Alice L., Watt, Stephen, Casale, Francesco Paolo, Sidiropoulos, Nikos, Rapin, Nicolas Philippe Jean-Pierre, Merkel, Angelika, Stunnenberg, Hendrik G, Stegle, Oliver, Frontini, Mattia, Downes, Kate, Pastinen, Tomi, Kuijpers, Taco W, Rico, Daniel, Valencia, Alfonso, Beck, Stephan, Soranzo, Nicole, Paul, Dirk S., Albers, Cornelis A., Amstislavskiy, Vyacheslav, Ashford, Sofie, Bomba, Lorenzo, Bujold, David, Burden, Frances, Busche, Stephan, Caron, Maxime, Chen, Shu-Huang, Cheung, Warren A., Clarke, Laura, Colgiu, Irina, Datta, Avik, Delaneau, Oliver, Elding, Heather, Farrow, Samantha, Garrido-Martín, Diego, Ge, Bing, Guigo, Roderic, Iotchkova, Valentina, Kundu, Kousik, Kwan, Tony, Lambourne, John J., Lowy, Ernesto, Mead, Daniel, Pourfarzad, Farzin, Redensek, Adriana, Rehnstrom, Karola, Rendon, Augusto, Richardson, David M., Risch, Thomas, Rowlston, Sophia, Shao, Xiaojian, Simon, Marie Michelle, Sultan, Marc, Walter, Klaudia, Wilder, Steven P., Yan, Ying, Antonarakis, Stylianos E., Bourque, Guillaume, Dermitzakis, Emmanouil T., Flicek, Paul, Lehrach, Hans, Martens, Joost H A, Yaspo, Marie-Laure, and Ouwehand, Willem H.
Subjects: DNA methylation, Neutrophils, Immune cells, T cells, Differential variability, Gene expression, Phenotypic plasticity, Heterogeneity, Monocytes
Abstract: Background: A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. Results: We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14+CD16-monocytes, CD66b+CD16+neutrophils, and CD4+CD45RA+naïve T cells from the same 125 healthy individuals. We discover substantially increased variability in neutrophils compared to monocytes and T cells. In neutrophils, genes with hypervariable expression are found to be implicated in key immune pathways and are associated with cellular properties and environmental exposure. We also observe increased sex-specific gene expression differences in neutrophils. Neutrophil-specific DNA methylation hypervariable sites are enriched at dynamic chromatin regions and active enhancers. Conclusions: Our data highlight the importance of transcriptional and epigenetic variability for the key role of neutrophils as the first responders to inflammatory stimuli. We provide a resource to enable further functional studies into the plasticity of immune cells, which can be accessed from: http://blueprint-dev.bioinfo.cnio.es/WP10/hypervariability.
Published: 2017

31. Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans

Author: Tuijnenburg, Paul, primary, Lango Allen, Hana, additional, Burns, Siobhan O., additional, Greene, Daniel, additional, Jansen, Machiel H., additional, Staples, Emily, additional, Stephens, Jonathan, additional, Carss, Keren J., additional, Biasci, Daniele, additional, Baxendale, Helen, additional, Thomas, Moira, additional, Chandra, Anita, additional, Kiani-Alikhan, Sorena, additional, Longhurst, Hilary J., additional, Seneviratne, Suranjith L., additional, Oksenhendler, Eric, additional, Simeoni, Ilenia, additional, de Bree, Godelieve J., additional, Tool, Anton T.J., additional, van Leeuwen, Ester M.M., additional, Ebberink, Eduard H.T.M., additional, Meijer, Alexander B., additional, Tuna, Salih, additional, Whitehorn, Deborah, additional, Brown, Matthew, additional, Turro, Ernest, additional, Thrasher, Adrian J., additional, Smith, Kenneth G.C., additional, Thaventhiran, James E., additional, Kuijpers, Taco W., additional, Adhya, Zoe, additional, Alachkar, Hana, additional, Anantharachagan, Ariharan, additional, Antrobus, Richard, additional, Arumugakani, Gururaj, additional, Bacchelli, Chiara, additional, Bethune, Claire, additional, Bibi, Shahnaz, additional, Boardman, Barbara, additional, Booth, Claire, additional, Browning, Michael, additional, Brownlie, Mary, additional, Burns, Siobhan, additional, Clifford, Hayley, additional, Cooper, Nichola, additional, Davies, Sophie, additional, Dempster, John, additional, Devlin, Lisa, additional, Doffinger, Rainer, additional, Drewe, Elizabeth, additional, Edgar, David, additional, Egner, William, additional, El-Shanawany, Tariq, additional, Gaspar, Bobby, additional, Ghurye, Rohit, additional, Gilmour, Kimberley, additional, Goddard, Sarah, additional, Gordins, Pavel, additional, Grigoriadou, Sofia, additional, Hackett, Scott, additional, Hague, Rosie, additional, Harper, Lorraine, additional, Hayman, Grant, additional, Herwadkar, Archana, additional, Hughes, Stephen, additional, Huissoon, Aarnoud, additional, Jolles, Stephen, additional, Jones, Julie, additional, Kelleher, Peter, additional, Klein, Nigel, additional, Kuijpers, Taco, additional, Kumararatne, Dinakantha, additional, Laffan, James, additional, Lear, Sara, additional, Longhurst, Hilary, additional, Lorenzo, Lorena, additional, Maimaris, Jesmeen, additional, Manson, Ania, additional, McDermott, Elizabeth, additional, Millar, Hazel, additional, Mistry, Anoop, additional, Morrisson, Valerie, additional, Murng, Sai, additional, Nasir, Iman, additional, Nejentsev, Sergey, additional, Noorani, Sadia, additional, Ponsford, Mark, additional, Qasim, Waseem, additional, Quinn, Ellen, additional, Quinti, Isabella, additional, Richter, Alex, additional, Samarghitean, Crina, additional, Sargur, Ravishankar, additional, Savic, Sinisa, additional, Seneviratne, Suranjith, additional, Sewall, Carrock, additional, Shackley, Fiona, additional, Stauss, Hans, additional, Steele, Cathal, additional, Thaventhiran, James, additional, Thrasher, Adrian, additional, Welch, Steve, additional, Willcocks, Lisa, additional, Workman, Sarita, additional, Worth, Austen, additional, Yeatman, Nigel, additional, Yong, Patrick, additional, Ashford, Sofie, additional, Bradley, John, additional, Fletcher, Debra, additional, Hammerton, Tracey, additional, James, Roger, additional, Kingston, Nathalie, additional, Ouwehand, Willem, additional, Penkett, Christopher, additional, Raymond, F Lucy, additional, Stirrups, Kathleen, additional, Veltman, Marijke, additional, Young, Tim, additional, Clements-Brod, Naomi, additional, Davis, John, additional, Dewhurst, Eleanor, additional, Erwood, Marie, additional, Frary, Amy, additional, Linger, Rachel, additional, Martin, Jennifer, additional, Papadia, Sofia, additional, Rehnstrom, Karola, additional, Astle, William, additional, Attwood, Antony, additional, Bleda, Marta, additional, Carss, Keren, additional, Daugherty, Louise, additional, Deevi, Sri, additional, Graf, Stefan, additional, Halmagyi, Csaba, additional, Haimel, Matthias, additional, Hu, Fengyuan, additional, Matser, Vera, additional, Meacham, Stuart, additional, Megy, Karyn, additional, Shamardina, Olga, additional, Titterton, Catherine, additional, Yu, Ping, additional, von Ziegenweldt, Julie, additional, Furnell, Abigail, additional, Mapeta, Rutendo, additional, Staines, Simon, additional, Rayner-Matthews, Paula, additional, and Watt, Christopher, additional
Published: 2018
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32. De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures

Author: Ito, Yoko, primary, Carss, Keren J., additional, Duarte, Sofia T., additional, Hartley, Taila, additional, Keren, Boris, additional, Kurian, Manju A., additional, Marey, Isabelle, additional, Charles, Perinne, additional, Mendonça, Carla, additional, Nava, Caroline, additional, Pfundt, Rolph, additional, Sanchis-Juan, Alba, additional, van Bokhoven, Hans, additional, van Essen, Anthony, additional, van Ravenswaaij-Arts, Conny, additional, Boycott, Kym M., additional, Kernohan, Kristin D., additional, Dyack, Sarah, additional, Raymond, F. Lucy, additional, Aitman, Timothy, additional, Bennett, David, additional, Caulfield, Mark, additional, Chinnery, Patrick, additional, Gale, Daniel, additional, Koziell, Ania, additional, Kuijpers, Taco W., additional, Laffan, Michael A., additional, Maher, Eamonn, additional, Markus, Hugh S., additional, Morrell, Nicholas W., additional, Ouwehand, Willem H., additional, Perry, David J., additional, Roberts, Irene, additional, Smith, Kenneth G.C., additional, Thrasher, Adrian, additional, Watkins, Hugh, additional, Williamson, Catherine, additional, Woods, Geoffrey, additional, Ashford, Sofie, additional, Bradley, John R., additional, Fletcher, Debra, additional, Hammerton, Tracey, additional, James, Roger, additional, Kingston, Nathalie, additional, Penkett, Christopher J., additional, Stirrups, Kathleen, additional, Veltman, Marijke, additional, Young, Tim, additional, Brown, Matthew, additional, Clements-Brod, Naomi, additional, Davis, John, additional, Dewhurst, Eleanor, additional, Dolling, Helen, additional, Erwood, Marie, additional, Frary, Amy, additional, Linger, Rachel, additional, Martin, Jennifer M., additional, Papadia, Sofia, additional, Rehnstrom, Karola, additional, Stark, Hannah, additional, Allsup, David, additional, Austin, Steve, additional, Bakchoul, Tamam, additional, Bariana, Tadbir K., additional, Bolton-Maggs, Paula, additional, Chalmers, Elizabeth, additional, Collins, Janine, additional, Collins, Peter, additional, Erber, Wendy N., additional, Everington, Tamara, additional, Favier, Remi, additional, Freson, Kathleen, additional, Furie, Bruce, additional, Gattens, Michael, additional, Gebhart, Johanna, additional, Gomez, Keith, additional, Greene, Daniel, additional, Greinacher, Andreas, additional, Gresele, Paolo, additional, Hart, Daniel, additional, Heemskerk, Johan W.M., additional, Henskens, Yvonne, additional, Kazmi, Rashid, additional, Keeling, David, additional, Kelly, Anne M., additional, Lambert, Michele P., additional, Lentaigne, Claire, additional, Liesner, Ri, additional, Makris, Mike, additional, Mangles, Sarah, additional, Mathias, Mary, additional, Millar, Carolyn M., additional, Mumford, Andrew, additional, Nurden, Paquita, additional, Payne, Jeanette, additional, Pasi, John, additional, Peerlinck, Kathelijne, additional, Revel-Vilk, Shoshana, additional, Richards, Michael, additional, Rondina, Matthew, additional, Roughley, Catherine, additional, Schulman, Sol, additional, Schulze, Harald, additional, Scully, Marie, additional, Sivapalaratnam, Suthesh, additional, Stubbs, Matthew, additional, Tait, R. Campbell, additional, Talks, Kate, additional, Thachil, Jecko, additional, Toh, Cheng-Hock, additional, Turro, Ernest, additional, Van Geet, Chris, additional, De Vries, Minka, additional, Warner, Timothy Q., additional, Watson, Henry, additional, Westbury, Sarah, additional, Furnell, Abigail, additional, Mapeta, Rutendo, additional, Rayner-Matthews, Paula, additional, Simeoni, Ilenia, additional, Staines, Simon, additional, Stephens, Jonathan, additional, Watt, Christopher, additional, Whitehorn, Deborah, additional, Attwood, Antony, additional, Daugherty, Louise, additional, Deevi, Sri V.V., additional, Halmagyi, Csaba, additional, Hu, Fengyuan, additional, Matser, Vera, additional, Meacham, Stuart, additional, Megy, Karyn, additional, Shamardina, Olga, additional, Titterton, Catherine, additional, Tuna, Salih, additional, Yu, Ping, additional, von Ziegenweldt, Julie, additional, Astle, William, additional, Bleda, Marta, additional, Gräf, Stefan, additional, Haimel, Matthias, additional, Lango-Allen, Hana, additional, Richardson, Sylvia, additional, Calleja, Paul, additional, Rankin, Stuart, additional, Turek, Wojciech, additional, Anderson, Julie, additional, Bryson, Christine, additional, Carmichael, Jenny, additional, McJannet, Coleen, additional, Stock, Sophie, additional, Allen, Louise, additional, Ambegaonkar, Gautum, additional, Armstrong, Ruth, additional, Arno, Gavin, additional, Bitner-Glindzicz, Maria, additional, Brady, Angie, additional, Canham, Natalie, additional, Chitre, Manali, additional, Clement, Emma, additional, Clowes, Virginia, additional, Deegan, Patrick, additional, Deshpande, Charu, additional, Doffinger, Rainer, additional, Firth, Helen, additional, Flinter, Frances, additional, French, Courtney, additional, Gardham, Alice, additional, Ghali, Neeti, additional, Gissen, Paul, additional, Grozeva, Detelina, additional, Henderson, Robert, additional, Hensiek, Anke, additional, Holden, Simon, additional, Holder, Muriel, additional, Holder, Susan, additional, Hurst, Jane, additional, Josifova, Dragana, additional, Krishnakumar, Deepa, additional, Lees, Melissa, additional, MacLaren, Robert, additional, Maw, Anna, additional, Mehta, Sarju, additional, Michaelides, Michel, additional, Moore, Anthony, additional, Murphy, Elaine, additional, Park, Soo-Mi, additional, Parker, Alasdair, additional, Patch, Chris, additional, Paterson, Joan, additional, Rankin, Julia, additional, Reid, Evan, additional, Rosser, Elisabeth, additional, Sandford, Richard, additional, Santra, Saikat, additional, Scott, Richard, additional, Sohal, Aman, additional, Stein, Penelope, additional, Thomas, Ellen, additional, Thompson, Dorothy, additional, Tischkowitz, Marc, additional, Vogt, Julie, additional, Wakeling, Emma, additional, Wassmer, Evangeline, additional, Webster, Andrew, additional, Ali, Sonia, additional, Ali, Souad, additional, Boggard, Harm J., additional, Church, Colin, additional, Coghlan, Gerry, additional, Cookson, Victoria, additional, Corris, Paul A., additional, Creaser-Myers, Amanda, additional, DaCosta, Rosa, additional, Dormand, Natalie, additional, Eyries, Mélanie, additional, Gall, Henning, additional, Ghataorhe, Pavandeep K., additional, Ghio, Stefano, additional, Ghofrani, Ardi, additional, Gibbs, J. Simon R., additional, Girerd, Barbara, additional, Greenhalgh, Alan, additional, Hadinnapola, Charaka, additional, Houweling, Arjan C., additional, Humbert, Marc, additional, in’t Veld, Anna Huis, additional, Kennedy, Fiona, additional, Kiely, David G., additional, Kovacs, Gabor, additional, Lawrie, Allan, additional, Ross, Rob V. Mackenzie, additional, Machado, Rajiv, additional, Masati, Larahmie, additional, Meehan, Sharon, additional, Moledina, Shahin, additional, Montani, David, additional, Othman, Shokri, additional, Peacock, Andrew J., additional, Pepke-Zaba, Joanna, additional, Pollock, Val, additional, Polwarth, Gary, additional, Ranganathan, Lavanya, additional, Rhodes, Christopher J., additional, Rue-Albrecht, Kevin, additional, Schotte, Gwen, additional, Shipley, Debbie, additional, Soubrier, Florent, additional, Southgate, Laura, additional, Scelsi, Laura, additional, Suntharalingam, Jay, additional, Tan, Yvonne, additional, Toshner, Mark, additional, Treacy, Carmen M., additional, Trembath, Richard, additional, Vonk Noordegraaf, Anton, additional, Walker, Sara, additional, Wanjiku, Ivy, additional, Wharton, John, additional, Wilkins, Martin, additional, Wort, Stephen J., additional, Yates, Katherine, additional, Alachkar, Hana, additional, Antrobus, Richard, additional, Arumugakani, Gururaj, additional, Bacchelli, Chiara, additional, Baxendale, Helen, additional, Bethune, Claire, additional, Bibi, Shahnaz, additional, Booth, Claire, additional, Browning, Michael, additional, Burns, Siobhan, additional, Chandra, Anita, additional, Cooper, Nichola, additional, Davies, Sophie, additional, Devlin, Lisa, additional, Drewe, Elizabeth, additional, Edgar, David, additional, Egner, William, additional, Ghurye, Rohit, additional, Gilmour, Kimberley, additional, Goddard, Sarah, additional, Gordins, Pavel, additional, Grigoriadou, Sofia, additional, Hackett, Scott, additional, Hague, Rosie, additional, Harper, Lorraine, additional, Hayman, Grant, additional, Herwadkar, Archana, additional, Huissoon, Aarnoud, additional, Jolles, Stephen, additional, Kelleher, Peter, additional, Kumararatne, Dinakantha, additional, Lear, Sara, additional, Longhurst, Hilary, additional, Lorenzo, Lorena, additional, Maimaris, Jesmeen, additional, Manson, Ania, additional, McDermott, Elizabeth, additional, Murng, Sai, additional, Nejentsev, Sergey, additional, Noorani, Sadia, additional, Oksenhendler, Eric, additional, Ponsford, Mark, additional, Qasim, Waseem, additional, Quinti, Isabella, additional, Richter, Alex, additional, Samarghitean, Crina, additional, Sargur, Ravishankar, additional, Savic, Sinisa, additional, Seneviratne, Suranjith, additional, Sewell, Carrock, additional, Staples, Emily, additional, Stauss, Hans, additional, Thaventhiran, James, additional, Thomas, Moira, additional, Welch, Steve, additional, Willcocks, Lisa, additional, Yeatman, Nigel, additional, Yong, Patrick, additional, Ancliff, Phil, additional, Babbs, Christian, additional, Layton, Mark, additional, Louka, Eleni, additional, McGowan, Simon, additional, Mead, Adam, additional, Roy, Noémi, additional, Chambers, Jenny, additional, Dixon, Peter, additional, Estiu, Cecelia, additional, Hague, Bill, additional, Marschall, Hanns-Ulrich, additional, Simpson, Michael, additional, Chong, Sam, additional, Emmerson, Ingrid, additional, Ginsberg, Lionel, additional, Gosal, David, additional, Hadden, Rob, additional, Horvath, Rita, additional, Mahdi-Rogers, Mohamed, additional, Manzur, Adnan, additional, Marshall, Andrew, additional, Matthews, Emma, additional, McCarthy, Mark, additional, Reilly, Mary, additional, Renton, Tara, additional, Rice, Andrew, additional, Themistocleous, Andreas, additional, Vale, Tom, additional, Van Zuydam, Natalie, additional, Walker, Suellen, additional, Ormondroyd, Liz, additional, Hudson, Gavin, additional, Wei, Wei, additional, Yu Wai Man, Patrick, additional, Whitworth, James, additional, Afzal, Maryam, additional, Colby, Elizabeth, additional, Saleem, Moin, additional, Alavijeh, Omid S., additional, Cook, H. Terry, additional, Johnson, Sally, additional, Levine, Adam P., additional, Wong, Edwin K.S., additional, Tan, Rhea, additional, MacKenzie, Alex, additional, Majewski, Jacek, additional, Brudno, Michael, additional, Bulman, Dennis, additional, and Dyment, David, additional
Published: 2018
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33. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Author: UMC Utrecht, Cardiovasculaire Epidemiologie, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Hendricks, Audrey E., Bochukova, Elena G., Marenne, Gaëlle, Keogh, Julia M., Atanassova, Neli, Bounds, Rebecca, Wheeler, Eleanor, Mistry, Vanisha, Henning, Elana, Körner, Antje, Muddyman, Dawn, McCarthy, Shane, Hinney, Anke, Hebebrand, Johannes, Scott, Robert A., Langenberg, Claudia, Wareham, Nick J., Surendran, Praveen, Howson, Joanna M M, Butterworth, Adam S., Danesh, John, Nordestgaard, Børge G., Nielsen, Sune F., Afzal, Shoaib, Papadia, Sofia, Ashford, Sofie, Garg, Sumedha, Millhauser, Glenn L., Palomino, Rafael I., Kwasniewska, Alexandra, Tachmazidou, Ioanna, O'Rahilly, Stephen, Zeggini, Eleftheria, Barroso, Inês, Farooqi, I. Sadaf, Benzeval, Michaela, Burton, Jonathan, Buck, Nicholas, Jäckle, Annette, Kumari, Meena, Laurie, Heather, Lynn, Peter, Pudney, Stephen, Rabe, Birgitta, Wolke, Dieter, Overvad, Kim, Tjønneland, Anne, Clavel-Chapelon, Francoise, Kaaks, Rudolf, Boeing, Heiner, Trichopoulou, Antonia, Ferrari, Pietro, Palli, Domenico, Krogha, Vittorio, Panico, Salvatore, Tuminoa, Rosario, Matullo, Giuseppe, Boer, Jolanda Ma, Van Der Schouw, Yvonne, Weiderpass, Elisabete, Quiros, J. Ramon, Sánchez, María José, Navarro, Carmen, Moreno-Iribas, Conchi, Arriola, Larraitz, Melander, Olle, Wennberg, Patrik, Key, Timothy J., Riboli, Elio, Al-Turki, Saeed, Anderson, Carl A, Anney, Richard, Antony, Dinu, Soler Artigas, María, Ayub, Muhammad, Bala, Senduran, Barrett, Jeffrey C, Beales, Phil, Bentham, Jamie, Bhattacharyaa, Shoumo, Birney, Ewan, Blackwooda, Douglas, Bobrow, Martin, Bolton, Patrick F., Boustred, Chris, Breen, Gerome, Calissanoa, Mattia, Carss, Keren, Charlton, Ruth, Chatterjee, Krishna, Chen, Lu, Ciampia, Antonio, Cirak, Sebahattin, Clapham, Peter, Clement, Gail, Coates, Guy, Coccaa, Massimiliano, Collier, David A, Cosgrove, Catherine, Coxa, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Danecek, Petr, Day, Ian N M, Day-Williams, Aaron G, Dominiczak, Anna, Down, Thomas, Du, Yuanping, Dunham, Ian, Durbin, Richard, Edkins, Sarah, Ekong, Rosemary, Ellis, Peter, Evansa, David M., FitzPatrick, David R., Flicek, Paul, Floyd, James S., Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Gallagher, Louise, Gaunt, Tom R., Geihs, Matthias, Geschwind, Daniel H., Greenwood, Celia M.T., Griffin, Heather, Grozeva, Detelina, Guo, Xiaosen, Guo, Xueqin, Gurling, Hugh, Hart, Deborah J., Holmans, Peter A, Howie, Bryan, Huang, Jie, Huang, Liren, Hubbard, Tim, Humphries, Steve E., Hurles, Matthew E., Hysi, Pirro G., Iotchkova, Valentina, Jackson, David K., Jamshidi, Yalda, Joyce, Chris, Karczewski, Konrad J., Kaye, Jane, Keane, Thomas, Kemp, John P., Kennedy, Karen, Kent, Alastair, Khawaja, Farrah, Van Kogelenberg, Margriet, Kolb-Kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Lek, Monkol, Li, Rui, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Lönnqvist, Jouko, Lopes, Luis R., Lopes, Margarida, MacArthur, Daniel G., Mangino, Massimo, Marchini, Jonathan, Maslen, John, Mathieson, Iain, McGuffin, Peter, McIntosh, Andrew M., McKechanie, Andrew G., McQuillin, Andrew, Memari, Yasin, Metrustry, Sarah, Migone, Nicola, Min, Josine L., Mitchison, Hannah M, Moayyeri, Alireza, Morris, Andrew D., Morris, James, Muntoni, Francesco, Northstone, Kate, O'Donovan, Michael C., Onoufriadis, Alexandros, Oualkacha, Karim, Owen, Michael J, Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R., Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Payne, Stewart J., Perry, John R. B., Pietilainen, Olli, Plagnol, Vincent, Pollitt, Rebecca C., Porteous, David J., Povey, Sue, Quail, Michael A., Quaye, Lydia, Raymond, F. Lucy, Rehnström, Karola, Richards, J Brent, Ridout, Cheryl K., Ring, Susan M., Ritchie, Graham R.S., Roberts, Nicola, Robinson, Rachel L., Savage, David B., Scambler, Peter, Schiffels, Stephan, Schmidts, Miriam, Schoenmakers, Nadia, Scott, Richard H., Semple, Robert K., Serra, Eva, Sharp, Sally I., Shaw, Adam, Shihab, Hashem A., Shin, So Youn, Skuse, David, Small, Kerrin S, Smee, Carol, Smith, Blair H., Davey Smith, George, Soranzo, Nicole, Southam, Lorraine, Spasic-Boskovic, Olivera, Spector, Timothy D, St Clair, David, St Pourcain, Beate, Stalker, Jim, Stevens, Elizabeth, Sun, Jianping, Surdulescu, Gabriela L, Suvisaari, Jaana, Syrris, Petros, Taylor, Rohan, Tian, Jing, Timpson, Nicholas J., Tobin, Martin D, Valdes, Ana M., Vandersteen, Anthony M., Vijayarangakannan, Parthiban, Visscher, Peter M., Wain, Louise V., Walter, Klaudia, Walters, James T.R., Wang, Guangbiao, Wang, Jun, Wang, Nai-Yu, Ward, Kirsten, Whyte, Tamieka, Williams, Hywel J., Williamson, Kathleen A., Wilson, Crispian, Wilson, Scott G., Wong, Kim, Xu, Changjiang, Yang, Jian, Zhang, Feng, Zhang, Pingbo, Zheng, Hou Feng, UMC Utrecht, Cardiovasculaire Epidemiologie, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Hendricks, Audrey E., Bochukova, Elena G., Marenne, Gaëlle, Keogh, Julia M., Atanassova, Neli, Bounds, Rebecca, Wheeler, Eleanor, Mistry, Vanisha, Henning, Elana, Körner, Antje, Muddyman, Dawn, McCarthy, Shane, Hinney, Anke, Hebebrand, Johannes, Scott, Robert A., Langenberg, Claudia, Wareham, Nick J., Surendran, Praveen, Howson, Joanna M M, Butterworth, Adam S., Danesh, John, Nordestgaard, Børge G., Nielsen, Sune F., Afzal, Shoaib, Papadia, Sofia, Ashford, Sofie, Garg, Sumedha, Millhauser, Glenn L., Palomino, Rafael I., Kwasniewska, Alexandra, Tachmazidou, Ioanna, O'Rahilly, Stephen, Zeggini, Eleftheria, Barroso, Inês, Farooqi, I. Sadaf, Benzeval, Michaela, Burton, Jonathan, Buck, Nicholas, Jäckle, Annette, Kumari, Meena, Laurie, Heather, Lynn, Peter, Pudney, Stephen, Rabe, Birgitta, Wolke, Dieter, Overvad, Kim, Tjønneland, Anne, Clavel-Chapelon, Francoise, Kaaks, Rudolf, Boeing, Heiner, Trichopoulou, Antonia, Ferrari, Pietro, Palli, Domenico, Krogha, Vittorio, Panico, Salvatore, Tuminoa, Rosario, Matullo, Giuseppe, Boer, Jolanda Ma, Van Der Schouw, Yvonne, Weiderpass, Elisabete, Quiros, J. Ramon, Sánchez, María José, Navarro, Carmen, Moreno-Iribas, Conchi, Arriola, Larraitz, Melander, Olle, Wennberg, Patrik, Key, Timothy J., Riboli, Elio, Al-Turki, Saeed, Anderson, Carl A, Anney, Richard, Antony, Dinu, Soler Artigas, María, Ayub, Muhammad, Bala, Senduran, Barrett, Jeffrey C, Beales, Phil, Bentham, Jamie, Bhattacharyaa, Shoumo, Birney, Ewan, Blackwooda, Douglas, Bobrow, Martin, Bolton, Patrick F., Boustred, Chris, Breen, Gerome, Calissanoa, Mattia, Carss, Keren, Charlton, Ruth, Chatterjee, Krishna, Chen, Lu, Ciampia, Antonio, Cirak, Sebahattin, Clapham, Peter, Clement, Gail, Coates, Guy, Coccaa, Massimiliano, Collier, David A, Cosgrove, Catherine, Coxa, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Danecek, Petr, Day, Ian N M, Day-Williams, Aaron G, Dominiczak, Anna, Down, Thomas, Du, Yuanping, Dunham, Ian, Durbin, Richard, Edkins, Sarah, Ekong, Rosemary, Ellis, Peter, Evansa, David M., FitzPatrick, David R., Flicek, Paul, Floyd, James S., Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Gallagher, Louise, Gaunt, Tom R., Geihs, Matthias, Geschwind, Daniel H., Greenwood, Celia M.T., Griffin, Heather, Grozeva, Detelina, Guo, Xiaosen, Guo, Xueqin, Gurling, Hugh, Hart, Deborah J., Holmans, Peter A, Howie, Bryan, Huang, Jie, Huang, Liren, Hubbard, Tim, Humphries, Steve E., Hurles, Matthew E., Hysi, Pirro G., Iotchkova, Valentina, Jackson, David K., Jamshidi, Yalda, Joyce, Chris, Karczewski, Konrad J., Kaye, Jane, Keane, Thomas, Kemp, John P., Kennedy, Karen, Kent, Alastair, Khawaja, Farrah, Van Kogelenberg, Margriet, Kolb-Kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Lek, Monkol, Li, Rui, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Lönnqvist, Jouko, Lopes, Luis R., Lopes, Margarida, MacArthur, Daniel G., Mangino, Massimo, Marchini, Jonathan, Maslen, John, Mathieson, Iain, McGuffin, Peter, McIntosh, Andrew M., McKechanie, Andrew G., McQuillin, Andrew, Memari, Yasin, Metrustry, Sarah, Migone, Nicola, Min, Josine L., Mitchison, Hannah M, Moayyeri, Alireza, Morris, Andrew D., Morris, James, Muntoni, Francesco, Northstone, Kate, O'Donovan, Michael C., Onoufriadis, Alexandros, Oualkacha, Karim, Owen, Michael J, Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R., Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Payne, Stewart J., Perry, John R. B., Pietilainen, Olli, Plagnol, Vincent, Pollitt, Rebecca C., Porteous, David J., Povey, Sue, Quail, Michael A., Quaye, Lydia, Raymond, F. Lucy, Rehnström, Karola, Richards, J Brent, Ridout, Cheryl K., Ring, Susan M., Ritchie, Graham R.S., Roberts, Nicola, Robinson, Rachel L., Savage, David B., Scambler, Peter, Schiffels, Stephan, Schmidts, Miriam, Schoenmakers, Nadia, Scott, Richard H., Semple, Robert K., Serra, Eva, Sharp, Sally I., Shaw, Adam, Shihab, Hashem A., Shin, So Youn, Skuse, David, Small, Kerrin S, Smee, Carol, Smith, Blair H., Davey Smith, George, Soranzo, Nicole, Southam, Lorraine, Spasic-Boskovic, Olivera, Spector, Timothy D, St Clair, David, St Pourcain, Beate, Stalker, Jim, Stevens, Elizabeth, Sun, Jianping, Surdulescu, Gabriela L, Suvisaari, Jaana, Syrris, Petros, Taylor, Rohan, Tian, Jing, Timpson, Nicholas J., Tobin, Martin D, Valdes, Ana M., Vandersteen, Anthony M., Vijayarangakannan, Parthiban, Visscher, Peter M., Wain, Louise V., Walter, Klaudia, Walters, James T.R., Wang, Guangbiao, Wang, Jun, Wang, Nai-Yu, Ward, Kirsten, Whyte, Tamieka, Williams, Hywel J., Williamson, Kathleen A., Wilson, Crispian, Wilson, Scott G., Wong, Kim, Xu, Changjiang, Yang, Jian, Zhang, Feng, Zhang, Pingbo, and Zheng, Hou Feng
Published: 2017

34. Erratum: Corrigendum: Common genetic variation drives molecular heterogeneity in human iPSCs

Author: Kilpinen, Helena, primary, Goncalves, Angela, additional, Leha, Andreas, additional, Afzal, Vackar, additional, Alasoo, Kaur, additional, Ashford, Sofie, additional, Bala, Sendu, additional, Bensaddek, Dalila, additional, Casale, Francesco Paolo, additional, Culley, Oliver J., additional, Danecek, Petr, additional, Faulconbridge, Adam, additional, Harrison, Peter W., additional, Kathuria, Annie, additional, McCarthy, Davis, additional, McCarthy, Shane A., additional, Meleckyte, Ruta, additional, Memari, Yasin, additional, Moens, Nathalie, additional, Soares, Filipa, additional, Mann, Alice, additional, Streeter, Ian, additional, Agu, Chukwuma A., additional, Alderton, Alex, additional, Nelson, Rachel, additional, Harper, Sarah, additional, Patel, Minal, additional, White, Alistair, additional, Patel, Sharad R., additional, Clarke, Laura, additional, Halai, Reena, additional, Kirton, Christopher M., additional, Kolb-Kokocinski, Anja, additional, Beales, Philip, additional, Birney, Ewan, additional, Danovi, Davide, additional, Lamond, Angus I., additional, Ouwehand, Willem H., additional, Vallier, Ludovic, additional, Watt, Fiona M., additional, Durbin, Richard, additional, Stegle, Oliver, additional, and Gaffney, Daniel J., additional
Published: 2017
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35. Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Author: Chen, Lu, primary, Ge, Bing, additional, Casale, Francesco Paolo, additional, Vasquez, Louella, additional, Kwan, Tony, additional, Garrido-Martín, Diego, additional, Watt, Stephen, additional, Yan, Ying, additional, Kundu, Kousik, additional, Ecker, Simone, additional, Datta, Avik, additional, Richardson, David, additional, Burden, Frances, additional, Mead, Daniel, additional, Mann, Alice L., additional, Fernandez, Jose Maria, additional, Rowlston, Sophia, additional, Wilder, Steven P., additional, Farrow, Samantha, additional, Shao, Xiaojian, additional, Lambourne, John J., additional, Redensek, Adriana, additional, Albers, Cornelis A., additional, Amstislavskiy, Vyacheslav, additional, Ashford, Sofie, additional, Berentsen, Kim, additional, Bomba, Lorenzo, additional, Bourque, Guillaume, additional, Bujold, David, additional, Busche, Stephan, additional, Caron, Maxime, additional, Chen, Shu-Huang, additional, Cheung, Warren, additional, Delaneau, Oliver, additional, Dermitzakis, Emmanouil T., additional, Elding, Heather, additional, Colgiu, Irina, additional, Bagger, Frederik O., additional, Flicek, Paul, additional, Habibi, Ehsan, additional, Iotchkova, Valentina, additional, Janssen-Megens, Eva, additional, Kim, Bowon, additional, Lehrach, Hans, additional, Lowy, Ernesto, additional, Mandoli, Amit, additional, Matarese, Filomena, additional, Maurano, Matthew T., additional, Morris, John A., additional, Pancaldi, Vera, additional, Pourfarzad, Farzin, additional, Rehnstrom, Karola, additional, Rendon, Augusto, additional, Risch, Thomas, additional, Sharifi, Nilofar, additional, Simon, Marie-Michelle, additional, Sultan, Marc, additional, Valencia, Alfonso, additional, Walter, Klaudia, additional, Wang, Shuang-Yin, additional, Frontini, Mattia, additional, Antonarakis, Stylianos E., additional, Clarke, Laura, additional, Yaspo, Marie-Laure, additional, Beck, Stephan, additional, Guigo, Roderic, additional, Rico, Daniel, additional, Martens, Joost H.A., additional, Ouwehand, Willem H., additional, Kuijpers, Taco W., additional, Paul, Dirk S., additional, Stunnenberg, Hendrik G., additional, Stegle, Oliver, additional, Downes, Kate, additional, Pastinen, Tomi, additional, and Soranzo, Nicole, additional
Published: 2016
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36. Phenotypic Characterization of EIF2AK4Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension

Author: Hadinnapola, Charaka, Bleda, Marta, Haimel, Matthias, Screaton, Nicholas, Swift, Andrew, Dorfmüller, Peter, Preston, Stephen D., Southwood, Mark, Hernandez-Sanchez, Jules, Martin, Jennifer, Treacy, Carmen, Yates, Katherine, Bogaard, Harm, Church, Colin, Coghlan, Gerry, Condliffe, Robin, Corris, Paul A., Gibbs, Simon, Girerd, Barbara, Holden, Simon, Humbert, Marc, Kiely, David G., Lawrie, Allan, Machado, Rajiv, MacKenzie Ross, Robert, Moledina, Shahin, Montani, David, Newnham, Michael, Peacock, Andrew, Pepke-Zaba, Joanna, Rayner-Matthews, Paula, Shamardina, Olga, Soubrier, Florent, Southgate, Laura, Suntharalingam, Jay, Toshner, Mark, Trembath, Richard, Noordegraaf, Anton Vonk, Wilkins, Martin R., Wort, Stephen J., Wharton, John, Gräf, Stefan, Morrell, Nicholas W., Aitman, Timothy, Bennett, David, Caulfield, Mark, Chinnery, Patrick, Gale, Daniel, Koziell, Ania, Kuijpers, Taco W, Laffan, Michael A, Maher, Eamonn, Markus, Hugh S, Ouwehand, Willem H, Perry, David, Raymond, F Lucy, Roberts, Irene, Smith, Kenneth, Thrasher, Adrian, Watkins, Hugh, Williamson, Catherine, Woods, Geoffrey, Ashford, Sofie, Bradley, John R, Fletcher, Debra, Hammerton, Tracey, James, Roger, Kingston, Nathalie, Ouwehand, Willem H, Penkett, Christopher J, Raymond, F Lucy, Stirrups, Kathleen, Veltman, Marijke, Young, Tim, Ashford, Sofie, Brown, Matthew, Clements-Brod, Naomi, Davis, John, Dewhurst, Eleanor, Erwood, Marie, Frary, Amy, Linger, Rachel, Papadia, Sofia, Rehnstrom, Karola, Stark, Hannah, Allsup, David, Austin, Steve, Bakchoul, Tamam, Bariana, Tadbir K, Bolton-Maggs, Paula, Chalmers, Elizabeth, Collins, Peter, Erber, Wendy N, Everington, Tamara, Favier, Remi, Freson, Kathleen, Furie, Bruce, Gattens, Michael, Gomez, Keith, Greene, Daniel, Greinacher, Andreas, Hart, Daniel, Heemskerk, Johan WM, Henskens, Yvonne, Kazmi, Rashid, Keeling, David, Kelly, Anne M, Laffan, Michael A, Lambert, Michele P, Lentaigne, Claire, Liesner, Ri, Mangles, Sarah, Mathias, Mary, Millar, Carolyn M, Mumford, Andrew, Nurden, Paquita, Ouwehand, Willem H, Papadia, Sofia, Payne, Jeanette, Pasi, John, Perry, David J, Peerlinck, Kathelijne, Richards, Michael, Rondina, Matthew, Roughley, Catherine, Schulman, Sol, Schulze, Harald, Scully, Marie, Sivapalaratnam, Suthesh, Tait, R Campbell, Talks, Kate, Thachil, Jecko, Turro, Ernest, Toh, Cheng-Hock, Van Geet, Chris, De Vries, Minka, Warner, Timothy Q, Westbury, Sarah, Furnell, Abigail, Mapeta, Rutendo, Simeoni, Ilenia, Staines, Simon, Stephens, Jonathan, Stirrups, Kathleen, Whitehorn, Deborah, Watt, Christopher, Attwood, Antony, Daugherty, Louise, Deevi, Sri VV, Halmagyi, Csaba, Hu, Fengyuan, James, Roger, Matser, Vera, Meacham, Stuart, Megy, Karyn, Penkett, Christopher J, Stirrups, Kathleen, Titterton, Catherine, Tuna, Salih, Yu, Ping, von Ziegenweldt, Julie, Astle, William, Carss, Keren, Greene, Daniel, Lango-Allen, Hana, Turro, Ernest, Astle, William, Greene, Daniel, Richardson, Sylvia, Turro, Ernest, Calleja, Paul, Rankin, Stuart, Turek, Wojciech, Bryson, Christine, Anderson, Julie, Fletcher, Debra, McJannet, Coleen, Stock, Sophie, Young, Tim, Wassmer, Evangeline, Sohal, Aman, Santra, Saikat, Vogt, Julie, Chitre, Manali, Krishnakumar, Deepa, Ambegaonkar, Gautum, Maw, Anna, Armstrong, Ruth, Park, Soo-Mi, Mehta, Sarju, Paterson, Joan, Carmichael, Jenny, Allen, Louise, Hensiek, Anke, Firth, Helen, Stein, Penelope, Deegan, Patrick, Doffinger, Rainer, Parker, Alasdair, Bitner-Glindzicz, Maria, Scott, Richard, Hurst, Jane, Rosser, Elisabeth, Lees, Melissa, Clement, Emma, Henderson, Robert, Thompson, Dorothy, Gardham, Alice, Gissen, Paul, Josifova, Dragana, Thomas, Ellen, Patch, Chris, Deshpande, Charu, Flinter, Frances, Holder, Muriel, Canham, Natalie, Wakeling, Emma, Holder, Susan, Ghali, Neeti, Brady, Angie, Clowes, Virginia, MacLaren, Robert, Webster, Andrew, Moore, Anthony, Arno, Gavin, Michaelides, Michel, Rankin, Julia, Kurian, Manju, Murphy, Elaine, Carss, Keren, Sanchis-Juan, Alba, Erwood, Marie, Dewhurst, Eleanor, Grozeva, Detelina, Raymond, F Lucy, Reid, Evan, Woods, Geoff, Tischkowitz, Marc, Sandford, Richard, Ali, Sonia, Creaser-Myers, Amanda, Cookson, Victoria, DaCosta, Rosa, Dormand, Natalie, Ghataorhe, Pavandeep K, Greenhalgh, Alan, Huis in’t Veld, Anna, Kennedy, Fiona, Mackenzie Ross, Rob, Masati, Larahmie, Meehan, Sharon, Othman, Shokri, Pollock, Val, Polwarth, Gary, Rhodes, Christopher J, Rue-Albrecht, Kevin, Schotte, Gwen, Shipley, Debbie, Tan, Yvonne, Wanjiku, Ivy, Wort, John, Smith, Kenneth, Kuijpers, Taco, Thrasher, Adrian, Thaventhiran, James, Brown, Matthew, Lango Allen, Hana, Simeoni, Ilenia, Staples, Emily, Samarghitean, Crina, Alachkar, Hana, Antrobus, Richard, Arumugakani, Gururaj, Bacchelli, Chiara, Baxendale, Helen, Bethune, Claire, Bibi, Shahnaz, Booth, Claire, Browning, Michael, Burns, Siobhan, Chandra, Anita, Cooper, Nichola, Davies, Sophie, Devlin, Lisa, Doffinger, Rainer, Drewe, Elizabeth, Edgar, David, Egner, William, Ghurye, Rohit, Gilmour, Kimberley, Goddard, Sarah, Gordins, Pavel, Grigoriadou, Sofia, Hackett, Scott, Hague, Rosie, Hayman, Grant, Herwadkar, Archana, Huissoon, Aarnoud, Jolles, Stephen, Kelleher, Peter, Kumararatne, Dinakantha, Lear, Sara, Longhurst, Hilary, Lorenzo, Lorena, Maimaris, Jesmeen, Manson, Ania, McDermott, Elizabeth, Murng, Sai, Nejentsev, Sergey, Noorani, Sadia, Oksenhendler, Eric, Ponsford, Mark, Qasim, Waseem, Quinti, Isabella, Richter, Alex, Sargur, Ravishankar, Savic, Sinisa, Seneviratne, Suranjith, Sewell, Carrock, Stauss, Hans, Thomas, Moira, Welch, Steve, Willcocks, Lisa, Yeatman, Nigel, and Yong, Patrick
Abstract: Supplemental Digital Content is available in the text.
Published: 2017
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37. KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation

Author: Pearce, Laura R, Atanassova, Neli, Banton, Matthew C, Bottomley, Bill, van der Klaauw, Agatha A, Revelli, Jean-Pierre, Hendricks, Audrey, Keogh, Julia M, Henning, Elana, Doree, Deon, Jeter-Jones, Sabrina, Garg, Sumedha, Bochukova, Elena G, Bounds, Rebecca, Ashford, Sofie, Gayton, Emma, Hindmarsh, Peter C, Shield, Julian PH, Crowne, Elizabeth, Barford, David, Wareham, Nick J, UK10K consortium, O'Rahilly, Stephen, Murphy, Michael P, Powell, David R, Barroso, Ines, Farooqi, I Sadaf, Keogh, Julia [0000-0002-0399-4114], Henning, Elana [0000-0002-0399-4114], Wareham, Nicholas [0000-0003-1422-2993], O'Rahilly, Stephen [0000-0003-2199-4449], Murphy, Mike [0000-0003-1115-9618], Barroso, Ines [0000-0001-5800-4520], Farooqi, Ismaa [0000-0001-7609-3504], and Apollo - University of Cambridge Repository
Subjects: Male, Models, Molecular, Proto-Oncogene Proteins B-raf, MAP Kinase Signaling System, Fatty Acids, Molecular Sequence Data, Age Factors, Hyperphagia, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Mice, Glucose, Animals, Humans, Female, Amino Acid Sequence, Obesity, Age of Onset, Insulin Resistance, Child, Energy Metabolism, Oxidation-Reduction, Sequence Alignment
Abstract: Kinase suppressor of Ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. We explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and 1,536 controls. We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in transfected cells; effects that can be ameliorated by the commonly prescribed antidiabetic drug, metformin. Mutation carriers exhibit hyperphagia in childhood, low heart rate, reduced basal metabolic rate and severe insulin resistance. These data establish KSR2 as an important regulator of energy intake, energy expenditure, and substrate utilization in humans. Modulation of KSR2-mediated effects may represent a novel therapeutic strategy for obesity and type 2 diabetes.
Published: 2013

38. Common genetic variation drives molecular heterogeneity in human IPSCs

Author: Kilpinen, Helena, primary, Goncalves, Angela, additional, Leha, Andreas, additional, Afzal, Vackar, additional, Ashford, Sofie, additional, Bala, Sendu, additional, Bensaddek, Dalila, additional, Casale, Francesco Paolo, additional, Culley, Oliver, additional, Danacek, Petr, additional, Faulconbridge, Adam, additional, Harrison, Peter, additional, McCarthy, Davis, additional, McCarthy, Shane A, additional, Meleckyte, Ruta, additional, Memari, Yasin, additional, Moens, Nathalie, additional, Soares, Filipa, additional, Streeter, Ian, additional, Agu, Chukwuma A, additional, Alderton, Alex, additional, Nelson, Rachel, additional, Harper, Sarah, additional, Patel, Minal, additional, Clarke, Laura, additional, Halai, Reena, additional, Kirton, Christopher M, additional, Kolb-Kokocinski, Anja, additional, Beales, Philip, additional, Birney, Ewan, additional, Danovi, Davide, additional, Lamond, Angus I, additional, Ouwehand, Willem H, additional, Vallier, Ludovic, additional, Watt, Fiona M, additional, Durbin, Richard, additional, Stegle, Oliver, additional, and Gaffney, Daniel J, additional
Published: 2016
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39. KSR2 Mutations Are Associated with Obesity, Insulin Resistance, and Impaired Cellular Fuel Oxidation

Author: Pearce, Laura R., primary, Atanassova, Neli, additional, Banton, Matthew C., additional, Bottomley, Bill, additional, van der Klaauw, Agatha A., additional, Revelli, Jean-Pierre, additional, Hendricks, Audrey, additional, Keogh, Julia M., additional, Henning, Elana, additional, Doree, Deon, additional, Jeter-Jones, Sabrina, additional, Garg, Sumedha, additional, Bochukova, Elena G., additional, Bounds, Rebecca, additional, Ashford, Sofie, additional, Gayton, Emma, additional, Hindmarsh, Peter C., additional, Shield, Julian P.H., additional, Crowne, Elizabeth, additional, Barford, David, additional, Wareham, Nick J., additional, O’Rahilly, Stephen, additional, Murphy, Michael P., additional, Powell, David R., additional, Barroso, Ines, additional, and Farooqi, I. Sadaf, additional
Published: 2013
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40. A dominant gain-of-function mutation in universal tyrosine kinase SRC causes thrombocytopenia, myelofibrosis, bleeding, and bone pathologies.

Author: Turro, Ernest, Greene, Daniel, Wijgaerts, Anouck, Thys, Chantal, Lentaigne, Claire, Bariana, Tadbir K., Westbury, Sarah K., Kelly, Anne M., Selleslag, Dominik, Stephens, Jonathan C., Papadia, Sofia, Simeoni, Ilenia, Penkett, Christopher J., Ashford, Sofie, Attwood, Antony, Austin, Steve, Bakchoul, Tamam, Collins, Peter, Deevi, Sri V. V., and Favier, Rémi
Subjects: GENETIC mutation, PROTEIN-tyrosine kinases, MYELOFIBROSIS, THROMBOCYTOPENIA, HEMORRHAGE, ONTOLOGY
Abstract: The article discusses the study on a gain-of-function-mutation in universal tyrosine kinase SRC which causes bone pathologies, bleeding, myelofibrosis, and thrombocytopenia. The study reportedly involved genome sequencing and human phenotype ontology patient coding to identify the mutation. Also explored are the characteristics of the genetic defect.
Published: 2016
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41. A gain-of-function variant in DIAPH1causes dominant macrothrombocytopenia and hearing loss

Author: Stritt, Simon, Nurden, Paquita, Turro, Ernest, Greene, Daniel, Jansen, Sjoert B., Westbury, Sarah K., Petersen, Romina, Astle, William J., Marlin, Sandrine, Bariana, Tadbir K., Kostadima, Myrto, Lentaigne, Claire, Maiwald, Stephanie, Papadia, Sofia, Kelly, Anne M., Stephens, Jonathan C., Penkett, Christopher J., Ashford, Sofie, Tuna, Salih, Austin, Steve, Bakchoul, Tamam, Collins, Peter, Favier, Rémi, Lambert, Michele P., Mathias, Mary, Millar, Carolyn M., Mapeta, Rutendo, Perry, David J., Schulman, Sol, Simeoni, Ilenia, Thys, Chantal, Gomez, Keith, Erber, Wendy N., Stirrups, Kathleen, Rendon, Augusto, Bradley, John R., van Geet, Chris, Raymond, F.Lucy, Laffan, Michael A., Nurden, Alan T., Nieswandt, Bernhard, Richardson, Sylvia, Freson, Kathleen, Ouwehand, Willem H., and Mumford, Andrew D.
Abstract: Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. In most MTP, this phenotype arises because of altered regulation of platelet formation from megakaryocytes (MKs). We report the identification of DIAPH1, which encodes the Rho-effector diaphanous-related formin 1 (DIAPH1), as a candidate gene for MTP using exome sequencing, ontological phenotyping, and similarity regression. We describe 2 unrelated pedigrees with MTP and sensorineural hearing loss that segregate with a DIAPH1R1213* variant predicting partial truncation of the DIAPH1 diaphanous autoregulatory domain. The R1213* variant was linked to reduced proplatelet formation from cultured MKs, cell clustering, and abnormal cortical filamentous actin. Similarly, in platelets, there was increased filamentous actin and stable microtubules, indicating constitutive activation of DIAPH1. Overexpression of DIAPH1 R1213* in cells reproduced the cytoskeletal alterations found in platelets. Our description of a novel disorder of platelet formation and hearing loss extends the repertoire of DIAPH1-related disease and provides new insight into the autoregulation of DIAPH1 activity.
Published: 2016
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42. Common genetic variation drives molecular heterogeneity in human iPSCs

Author: Kilpinen, Helena, Goncalves, Angela, Leha, Andreas, Afzal, Vackar, Alasoo, Kaur, Ashford, Sofie, Bala, Sendu, Bensaddek, Dalila, Casale, Francesco Paolo, Culley, Oliver J, Danecek, Petr, Faulconbridge, Adam, Harrison, Peter W, Kathuria, Annie, McCarthy, Davis, McCarthy, Shane A, Meleckyte, Ruta, Memari, Yasin, Moens, Nathalie, Soares, Filipa, Mann, Alice, Streeter, Ian, Agu, Chukwuma A, Alderton, Alex, Nelson, Rachel, Harper, Sarah, Patel, Minal, White, Alistair, Patel, Sharad R, Clarke, Laura, Halai, Reena, Kirton, Christopher M, Kolb-Kokocinski, Anja, Beales, Philip, Birney, Ewan, Danovi, Davide, Lamond, Angus I, Ouwehand, Willem H, Vallier, Ludovic, Watt, Fiona M, Durbin, Richard, Stegle, Oliver, and Gaffney, Daniel J
Subjects: Quality Control, DNA Copy Number Variations, Genotype, Induced Pluripotent Stem Cells, Quantitative Trait Loci, Genetic Variation, Cellular Reprogramming, 3. Good health, Phenotype, Gene Expression Regulation, Organ Specificity, Humans, Transcriptome, Cells, Cultured
Abstract: Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

43. A dominant gain-of-function mutation in universal tyrosine kinase SRCcauses thrombocytopenia, myelofibrosis, bleeding, and bone pathologies

Author: Turro, Ernest, Greene, Daniel, Wijgaerts, Anouck, Thys, Chantal, Lentaigne, Claire, Bariana, Tadbir K., Westbury, Sarah K., Kelly, Anne M., Selleslag, Dominik, Stephens, Jonathan C., Papadia, Sofia, Simeoni, Ilenia, Penkett, Christopher J., Ashford, Sofie, Attwood, Antony, Austin, Steve, Bakchoul, Tamam, Collins, Peter, Deevi, Sri V. V., Favier, Rémi, Kostadima, Myrto, Lambert, Michele P., Mathias, Mary, Millar, Carolyn M., Peerlinck, Kathelijne, Perry, David J., Schulman, Sol, Whitehorn, Deborah, Wittevrongel, Christine, De Maeyer, Marc, Rendon, Augusto, Gomez, Keith, Erber, Wendy N., Mumford, Andrew D., Nurden, Paquita, Stirrups, Kathleen, Bradley, John R., Lucy Raymond, F., Laffan, Michael A., Van Geet, Chris, Richardson, Sylvia, Freson, Kathleen, and Ouwehand, Willem H.
Abstract: E527K hyperactive SRC results in megakaryocytes with increased podosome formation, thrombocytopenia, myelofibrosis, bleeding, and bone pathologies.
Published: 2016
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44. SMIM1 absence is associated with reduced energy expenditure and excess weight.

Author: Stefanucci L, Moslemi C, Tomé AR, Virtue S, Bidault G, Gleadall NS, Watson LPE, Kwa JE, Burden F, Farrow S, Chen J, Võsa U, Burling K, Walker L, Ord J, Barker P, Warner J, Frary A, Renhstrom K, Ashford SE, Piper J, Biggs G, Erber WN, Hoffman GJ, Schoenmakers N, Erikstrup C, Rieneck K, Dziegiel MH, Ullum H, Azzu V, Vacca M, Aparicio HJ, Hui Q, Cho K, Sun YV, Wilson PW, Bayraktar OA, Vidal-Puig A, Ostrowski SR, Astle WJ, Olsson ML, Storry JR, Pedersen OB, Ouwehand WH, Chatterjee K, Vuckovic D, and Frontini M
Subjects: Adult, Female, Humans, Male, Middle Aged, Adiponectin genetics, Adiponectin metabolism, Case-Control Studies, Loss of Function Mutation, Membrane Proteins genetics, Overweight genetics, Thyroid Hormones blood, Thyroid Hormones metabolism, Energy Metabolism genetics, Leptin blood, Leptin genetics, Leptin metabolism, Obesity genetics, Obesity metabolism
Abstract: Background: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments., Methods: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1 -/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan., Findings: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure., Conclusion: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them., Funding: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant., Competing Interests: Declaration of interests J.S. is the deputy CEO and 50% owner of BLUsang AB. He holds patents on Vel genotyping (inventors: Jill Storry, Magnus Jöud, Björn Nilsson, and Martin L. Olsson). J.S. has received speaker fees, royalties, and honoraria from the following companies: Grifols Diagnostic Solutions, QuidelOrtho Inc., and Biorad Laboratories. J.S. receives an honorarium for Section Editor work, Vox Sanguinis from John Wiley & Sons Ltd. J.S. is Vice President of the International Society of Blood Transfusion and married to Professor M.L.O. M.L.O. is CEO and 50% owner of BLUsang AB. M.L.O. holds patents on Vel genotyping (inventors: Jill Storry, Magnus Jöud, Björn Nilsson, and Martin L. Olsson). M.L.O. received speaker fees, royalties, and honoraria from the following companies: Grifols Diagnostic Solutions, QuidelOrtho Inc., and Biorad Laboratories. M.L.O. is married to Adjunct Professor J.S. W.N.E. is chair of the International Council for Standardization in Haematology. W.N.E. works as advisor for Scorpio Labs and is on the editorial board of the Journal of Clinical Pathology. W.H.O. is chair of the Blood Transfusion Genomics Consortium. W.H.O. is in receipt of an educational/research grant from Thermo Fisher Scientific. N.G. offers scientific consulting services to Thermo Fisher Scientific., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2024
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45. Whole-genome sequencing of patients with rare diseases in a national health system.

Author: Turro E, Astle WJ, Megy K, Gräf S, Greene D, Shamardina O, Allen HL, Sanchis-Juan A, Frontini M, Thys C, Stephens J, Mapeta R, Burren OS, Downes K, Haimel M, Tuna S, Deevi SVV, Aitman TJ, Bennett DL, Calleja P, Carss K, Caulfield MJ, Chinnery PF, Dixon PH, Gale DP, James R, Koziell A, Laffan MA, Levine AP, Maher ER, Markus HS, Morales J, Morrell NW, Mumford AD, Ormondroyd E, Rankin S, Rendon A, Richardson S, Roberts I, Roy NBA, Saleem MA, Smith KGC, Stark H, Tan RYY, Themistocleous AC, Thrasher AJ, Watkins H, Webster AR, Wilkins MR, Williamson C, Whitworth J, Humphray S, Bentley DR, Kingston N, Walker N, Bradley JR, Ashford S, Penkett CJ, Freson K, Stirrups KE, Raymond FL, and Ouwehand WH
Subjects: Actin-Related Protein 2-3 Complex genetics, Adaptor Proteins, Signal Transducing genetics, Alleles, Databases, Factual, Erythrocytes metabolism, GATA1 Transcription Factor genetics, Humans, Phenotype, Quantitative Trait Loci, Receptors, Thrombopoietin genetics, State Medicine, United Kingdom, Internationality, National Health Programs, Rare Diseases diagnosis, Rare Diseases genetics, Whole Genome Sequencing
Abstract: Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered 1 . Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants 2 , we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
Published: 2020
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46. Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy.

Author: Levine AP, Chan MMY, Sadeghi-Alavijeh O, Wong EKS, Cook HT, Ashford S, Carss K, Christian MT, Hall M, Harris CL, McAlinden P, Marchbank KJ, Marks SD, Maxwell H, Megy K, Penkett CJ, Mozere M, Stirrups KE, Tuna S, Wessels J, Whitehorn D, Johnson SA, and Gale DP
Subjects: Complement C3 Nephritic Factor analysis, Female, Glomerulonephritis, Membranoproliferative etiology, HLA-DQ Antigens genetics, HLA-DR Antigens genetics, Humans, Male, Serogroup, Complement C3 immunology, Glomerulonephritis, Membranoproliferative genetics, Whole Genome Sequencing
Abstract: Background: Primary membranoproliferative GN, including complement 3 (C3) glomerulopathy, is a rare, untreatable kidney disease characterized by glomerular complement deposition. Complement gene mutations can cause familial C3 glomerulopathy, and studies have reported rare variants in complement genes in nonfamilial primary membranoproliferative GN., Methods: We analyzed whole-genome sequence data from 165 primary membranoproliferative GN cases and 10,250 individuals without the condition (controls) as part of the National Institutes of Health Research BioResource-Rare Diseases Study. We examined copy number, rare, and common variants., Results: Our analysis included 146 primary membranoproliferative GN cases and 6442 controls who were unrelated and of European ancestry. We observed no significant enrichment of rare variants in candidate genes (genes encoding components of the complement alternative pathway and other genes associated with the related disease atypical hemolytic uremic syndrome; 6.8% in cases versus 5.9% in controls) or exome-wide. However, a significant common variant locus was identified at 6p21.32 (rs35406322) ( P =3.29×10 -8 ; odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.53 to 2.44), overlapping the HLA locus. Imputation of HLA types mapped this signal to a haplotype incorporating DQA1*05:01, DQB1*02:01, and DRB1*03:01 ( P =1.21×10 -8 ; OR, 2.19; 95% CI, 1.66 to 2.89). This finding was replicated by analysis of HLA serotypes in 338 individuals with membranoproliferative GN and 15,614 individuals with nonimmune renal failure., Conclusions: We found that HLA type, but not rare complement gene variation, is associated with primary membranoproliferative GN. These findings challenge the paradigm of complement gene mutations typically causing primary membranoproliferative GN and implicate an underlying autoimmune mechanism in most cases., (Copyright © 2020 by the American Society of Nephrology.)
Published: 2020
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47. Germline selection shapes human mitochondrial DNA diversity.

Author: Wei W, Tuna S, Keogh MJ, Smith KR, Aitman TJ, Beales PL, Bennett DL, Gale DP, Bitner-Glindzicz MAK, Black GC, Brennan P, Elliott P, Flinter FA, Floto RA, Houlden H, Irving M, Koziell A, Maher ER, Markus HS, Morrell NW, Newman WG, Roberts I, Sayer JA, Smith KGC, Taylor JC, Watkins H, Webster AR, Wilkie AOM, Williamson C, Ashford S, Penkett CJ, Stirrups KE, Rendon A, Ouwehand WH, Bradley JR, Raymond FL, Caulfield M, Turro E, and Chinnery PF
Subjects: Female, Genetic Variation, Humans, DNA, Mitochondrial genetics, Genome, Mitochondrial, Maternal Inheritance, Ovum growth & development, Selection, Genetic
Abstract: Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother-offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Published: 2019
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48. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity.

Author: Hendricks AE, Bochukova EG, Marenne G, Keogh JM, Atanassova N, Bounds R, Wheeler E, Mistry V, Henning E, Körner A, Muddyman D, McCarthy S, Hinney A, Hebebrand J, Scott RA, Langenberg C, Wareham NJ, Surendran P, Howson JM, Butterworth AS, Danesh J, Nordestgaard BG, Nielsen SF, Afzal S, Papadia S, Ashford S, Garg S, Millhauser GL, Palomino RI, Kwasniewska A, Tachmazidou I, O'Rahilly S, Zeggini E, Barroso I, and Farooqi IS
Subjects: Animals, Case-Control Studies, Chromogranins chemistry, Chromogranins genetics, Chromogranins metabolism, Female, GTP-Binding Protein alpha Subunits, Gs chemistry, GTP-Binding Protein alpha Subunits, Gs genetics, GTP-Binding Protein alpha Subunits, Gs metabolism, Humans, Male, Mice, Models, Molecular, Mutation, Obesity, Morbid diagnosis, Odds Ratio, Pediatric Obesity diagnosis, Pedigree, Protein Conformation, Rodentia, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Obesity, Morbid genetics, Pediatric Obesity genetics
Abstract: Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF~0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10 -3 ), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.
Published: 2017
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49. Prospective study of insulin-like growth factor-I, insulin-like growth factor-binding protein 3, genetic variants in the IGF1 and IGFBP3 genes and risk of coronary artery disease.

Author: Ricketts SL, Rensing KL, Holly JM, Chen L, Young EH, Luben R, Ashford S, Song K, Yuan X, Dehghan A, Wright BJ, Waterworth DM, Mooser V, Waeber G, Vollenweider P, Epstein SE, Burnett MS, Devaney JM, Hakonarson HH, Rader DJ, Reilly MP, Danesh J, Thompson SG, Dunning AM, van Duijn CM, Samani NJ, McPherson R, Wareham NJ, Khaw KT, Boekholdt SM, and Sandhu MS
Abstract: Although experimental studies have suggested that insulin-like growth factor I (IGF-I) and its binding protein IGFBP-3 might have a role in the aetiology of coronary artery disease (CAD), the relevance of circulating IGFs and their binding proteins in the development of CAD in human populations is unclear. We conducted a nested case-control study, with a mean follow-up of six years, within the EPIC-Norfolk cohort to assess the association between circulating levels of IGF-I and IGFBP-3 and risk of CAD in up to 1,013 cases and 2,055 controls matched for age, sex and study enrolment date. After adjustment for cardiovascular risk factors, we found no association between circulating levels of IGF-I or IGFBP-3 and risk of CAD (odds ratio: 0.98 (95% Cl 0.90-1.06) per 1 SD increase in circulating IGF-I; odds ratio: 1.02 (95% Cl 0.94-1.12) for IGFBP-3). We examined associations between tagging single nucleotide polymorphisms (tSNPs) at the IGF1 and IGFBP3 loci and circulating IGF-I and IGFBP-3 levels in up to 1,133 cases and 2,223 controls and identified three tSNPs (rs1520220, rs3730204, rs2132571) that showed independent association with either circulating IGF-I or IGFBP-3 levels. In an assessment of 31 SNPs spanning the IGF1 or IGFBP3 loci, none were associated with risk of CAD in a meta-analysis that included EPIC-Norfolk and eight additional studies comprising up to 9,319 cases and 19,964 controls. Our results indicate that IGF-I and IGFBP-3 are unlikely to be importantly involved in the aetiology of CAD in human populations.
Published: 2011

50. Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

Author: Waterworth DM, Ricketts SL, Song K, Chen L, Zhao JH, Ripatti S, Aulchenko YS, Zhang W, Yuan X, Lim N, Luan J, Ashford S, Wheeler E, Young EH, Hadley D, Thompson JR, Braund PS, Johnson T, Struchalin M, Surakka I, Luben R, Khaw KT, Rodwell SA, Loos RJ, Boekholdt SM, Inouye M, Deloukas P, Elliott P, Schlessinger D, Sanna S, Scuteri A, Jackson A, Mohlke KL, Tuomilehto J, Roberts R, Stewart A, Kesäniemi YA, Mahley RW, Grundy SM, McArdle W, Cardon L, Waeber G, Vollenweider P, Chambers JC, Boehnke M, Abecasis GR, Salomaa V, Järvelin MR, Ruokonen A, Barroso I, Epstein SE, Hakonarson HH, Rader DJ, Reilly MP, Witteman JC, Hall AS, Samani NJ, Strachan DP, Barter P, van Duijn CM, Kooner JS, Peltonen L, Wareham NJ, McPherson R, Mooser V, and Sandhu MS
Subjects: Asian People, Cholesterol, HDL blood, Cholesterol, LDL blood, Genetic Variation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors, Triglycerides blood, White People, Cholesterol, HDL genetics, Cholesterol, LDL genetics, Coronary Artery Disease genetics, Lipid Metabolism genetics, Triglycerides genetics
Abstract: Objective: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides., Methods and Results: We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9))., Conclusions: We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.
Published: 2010
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