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155 results on '"Memari, Yasin"'

1. Large-scale analysis of whole genome sequencing data from formalin-fixed paraffin-embedded cancer specimens demonstrates preservation of clinical utility

Author

Basyuni, Shadi, Heskin, Laura, Degasperi, Andrea, Black, Daniella, Koh, Gene C. C., Chmelova, Lucia, Rinaldi, Giuseppe, Bell, Steven, Grybowicz, Louise, Elgar, Greg, Memari, Yasin, Robbe, Pauline, Kingsbury, Zoya, Caldas, Carlos, Abraham, Jean, Schuh, Anna, Jones, Louise, Tischkowitz, Marc, Brown, Matthew A., Davies, Helen R., and Nik-Zainal, Serena

Published
2024
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3. Insights from multi-omic modeling of neurodegeneration in xeroderma pigmentosum using an induced pluripotent stem cell system

Author

Badja, Cherif, Momen, Sophie, Koh, Gene Ching Chiek, Boushaki, Soraya, Roumeliotis, Theodoros I., Kozik, Zuza, Jones, Ian, Bousgouni, Vicky, Dias, João M.L., Krokidis, Marios G., Young, Jamie, Chen, Hongwei, Yang, Ming, Docquier, France, Memari, Yasin, Valcarcel-Zimenez, Lorea, Gupta, Komal, Kong, Li Ren, Fawcett, Heather, Robert, Florian, Zhao, Salome, Degasperi, Andrea, Kumar, Yogesh, Davies, Helen, Harris, Rebecca, Frezza, Christian, Chatgilialoglu, Chryssostomos, Sarkany, Robert, Lehmann, Alan, Bakal, Chris, Choudhary, Jyoti, Fassihi, Hiva, and Nik-Zainal, Serena

Published
2024
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4. Low incidence rate of COVID-19 undermines confidence in estimation of the vaccine efficacy

Author

Memari, Yasin

Subjects
Statistics - Methodology, Statistics - Applications
Abstract

Knowing the true effect size of clinical interventions in randomised clinical trials is key to informing the public health policies. Vaccine efficacy is defined in terms of the relative risk or the ratio of two disease risks. However, only approximate methods are available for estimating the variance of the relative risk. In this article, we show using a probabilistic model that uncertainty in the efficacy rate could be underestimated when the disease risk is low. Factoring in the baseline rate of the disease, we estimate broader confidence intervals for the efficacy rates of the vaccines recently developed for COVID-19. We propose new confidence intervals for the relative risk. We further show that sample sizes required for phase 3 efficacy trials are routinely underestimated and propose a new method for sample size calculation where the efficacy is of interest. We also discuss the deleterious effects of classification bias which is particularly relevant at low disease prevalence.

Published
2021

6. Functional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based BRCAness tests

Author

Meijer, Titia G., Nguyen, Luan, Van Hoeck, Arne, Sieuwerts, Anieta M., Verkaik, Nicole S., Ladan, Marjolijn M., Ruigrok-Ritstier, Kirsten, van Deurzen, Carolien H. M., van de Werken, Harmen J. G., Lips, Esther H., Linn, Sabine C., Memari, Yasin, Davies, Helen, Nik-Zainal, Serena, Kanaar, Roland, Martens, John W. M., Cuppen, Edwin, Jager, Agnes, and van Gent, Dik C.

Published
2022
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8. Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture

Author

Zheng, Hou‐Feng, Forgetta, Vincenzo, Hsu, Yi‐Hsiang, Estrada, Karol, Rosello‐Diez, Alberto, Leo, Paul J, Dahia, Chitra L, Park‐Min, Kyung Hyun, Tobias, Jonathan H, Kooperberg, Charles, Kleinman, Aaron, Styrkarsdottir, Unnur, Liu, Ching‐Ti, Uggla, Charlotta, Evans, Daniel S, Nielson, Carrie M, Walter, Klaudia, Pettersson‐Kymmer, Ulrika, McCarthy, Shane, Eriksson, Joel, Kwan, Tony, Jhamai, Mila, Trajanoska, Katerina, Memari, Yasin, Min, Josine, Huang, Jie, Danecek, Petr, Wilmot, Beth, Li, Rui, Chou, Wen‐Chi, Mokry, Lauren E, Moayyeri, Alireza, Claussnitzer, Melina, Cheng, Chia‐Ho, Cheung, Warren, Medina‐Gómez, Carolina, Ge, Bing, Chen, Shu‐Huang, Choi, Kwangbom, Oei, Ling, Fraser, James, Kraaij, Robert, Hibbs, Matthew A, Gregson, Celia L, Paquette, Denis, Hofman, Albert, Wibom, Carl, Tranah, Gregory J, Marshall, Mhairi, Gardiner, Brooke B, Cremin, Katie, Auer, Paul, Hsu, Li, Ring, Sue, Tung, Joyce Y, Thorleifsson, Gudmar, Enneman, Anke W, van Schoor, Natasja M, de Groot, Lisette CPGM, van der Velde, Nathalie, Melin, Beatrice, Kemp, John P, Christiansen, Claus, Sayers, Adrian, Zhou, Yanhua, Calderari, Sophie, van Rooij, Jeroen, Carlson, Chris, Peters, Ulrike, Berlivet, Soizik, Dostie, Josée, Uitterlinden, Andre G, Williams, Stephen R, Farber, Charles, Grinberg, Daniel, LaCroix, Andrea Z, Haessler, Jeff, Chasman, Daniel I, Giulianini, Franco, Rose, Lynda M, Ridker, Paul M, Eisman, John A, Nguyen, Tuan V, Center, Jacqueline R, Nogues, Xavier, Garcia‐Giralt, Natalia, Launer, Lenore L, Gudnason, Vilmunder, Mellström, Dan, Vandenput, Liesbeth, Amin, Najaf, van Duijn, Cornelia M, Karlsson, Magnus K, Ljunggren, Östen, Svensson, Olle, Hallmans, Göran, Rousseau, François, Giroux, Sylvie, Bussière, Johanne, and Arp, Pascal P

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Genetics, Human Genome, Biotechnology, Osteoporosis, Stem Cell Research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, Underpinning research, Musculoskeletal, Injuries and accidents, Animals, Bone Density, Bone and Bones, Disease Models, Animal, Europe, Exome, Female, Fractures, Bone, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genomics, Genotype, Homeodomain Proteins, Humans, Mice, Sequence Analysis, DNA, White People, Wnt Proteins, AOGC Consortium, UK10K Consortium, General Science & Technology
Abstract

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Published
2015

10. Cosmological parameter estimation with QUaD CMB polarization and temperature experiment

Author

Memari, Yasin, Taylor, Andy., and Castro, Patricia

Subjects
520, flat sky, cosmic microwave background radiation, QUaD
Abstract

In this thesis we examine the theoretical origin and statistical features of the Cosmic Microwave Background radiation. We particularly focus on the CMB power spectra and cosmological parameter estimation from QUaD CMB experiment data in order to derive implications for the concordance cosmological model. In chapter 4 we present a detailed parameter estimation analysis of the combined polarization and temperature power spectra from the second and third season observations of the QUaD experiment. QUaD has for the first time detected multiple acoustic peaks in the polarization spectrum, allowing meaningful parameter analyses from the polarization data alone. In a standard 6-parameter ACDM parameter estimation analysis we find the QUaD TT power spectrum to be in very good agreement with previous results. However, the QUaD polarization data shows some tension with ACDM model. The origin of this 1−2σ tension remains unclear, and may point to new physics, residual systematics or simple random chance. Combining polarization and temperature data we find an acceptable fit, and show that our results are dominated by the polarization signal. We combine QUaD with the five-year data from the WMAP satellite and the SDSS Luminous Red Galaxies 4th data release power spectrum, and extend our analysis to constrain the tensor-to-scalar ratio and the primordial isocurvature perturbations. Our analysis sets a benchmark for future polarization experiments. In chapter 5 we outline and test a new semi-analytical approach for the estimation of the pseudo- temperature and polarization CMB power spectra for experiments with incomplete sky coverage. We propose a method for constructing the mode-mode coupling matrices which connect the temperature and polarization pseudo-Cℓ’s to the unbiased all-sky bandpowers in the flat sky approximation. We apply this method to the apodization masks of the QUaD CMB experiment and we show that the true underlying bandpowers can be reconstructed from the simulated QUaD-like pseudo-Cℓ’s to high precision. We further investigate the possibility of extending the proposed analytical flat sky approach to the exact calculation of the PCL covariance matrices over a large range of multipoles and we find that the numerical calculation is extremely computationally expensive. The flat sky pseudo-Cℓ and covariances methods presented in this chapter are still work in progress and require more testing.

Published
2009

11. CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module

Author

Dougherty, Gerard W., Mizuno, Katsutoshi, Nöthe-Menchen, Tabea, Ikawa, Yayoi, Boldt, Karsten, Ta-Shma, Asaf, Aprea, Isabella, Minegishi, Katsura, Pang, Yuan-Ping, Pennekamp, Petra, Loges, Niki T., Raidt, Johanna, Hjeij, Rim, Wallmeier, Julia, Mussaffi, Huda, Perles, Zeev, Elpeleg, Orly, Rabert, Franziska, Shiratori, Hidetaka, Letteboer, Stef J., Horn, Nicola, Young, Samuel, Strünker, Timo, Stumme, Friederike, Werner, Claudius, Olbrich, Heike, Takaoka, Katsuyoshi, Ide, Takahiro, Twan, Wang Kyaw, Biebach, Luisa, Große-Onnebrink, Jörg, Klinkenbusch, Judith A., Praveen, Kavita, Bracht, Diana C., Höben, Inga M., Junger, Katrin, Gützlaff, Jana, Cindrić, Sandra, Aviram, Micha, Kaiser, Thomas, Memari, Yasin, Dzeja, Petras P., Dworniczak, Bernd, Ueffing, Marius, Roepman, Ronald, Bartscherer, Kerstin, Katsanis, Nicholas, Davis, Erica E., Amirav, Israel, Hamada, Hiroshi, and Omran, Heymut

Published
2020
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12. A rare genetic disorder provides insights into mechanisms of early-onset neurodegeneration

Author

Badja, Cherif, primary, Momen, Sophie, additional, Koh, Gene Ching Cheik, additional, Boushaki, Soraya, additional, Roumeliotis, Theodoros I., additional, Kozik, Zuza, additional, Jones, Ian, additional, Bousgouni, Vicky, additional, Dias, Joao M. L., additional, Krokidis, Marios, additional, Young, Jamie, additional, Chen, Hongwei, additional, Yang, Ming, additional, Docquier, France, additional, Memari, Yasin, additional, Valcarcel-Jimenez, Lorea, additional, Gupta, Komal, additional, Kong, Li Ren, additional, Fawcett, Heather, additional, Robert, Florian, additional, Zhao, Salome, additional, Degasperi, Andrea, additional, Davies, Helen, additional, Harris, Rebecca, additional, Frezza, Christian, additional, Chatgilialoglu, Chryssostomos, additional, Sarkany, Robert, additional, Lehmann, Alan, additional, Bakal, Chris, additional, Choudhary, Jyoti, additional, Fassihi, Hiva, additional, and Nik-Zainal, Serena, additional

Published
2023
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13. Large Scale Analysis of Whole Genome Sequencing Data from Formalin-Fixed Paraffin-Embedded Cancer Specimens Demonstrates Preservation of Clinical Utility Enhancing Accessibility to Genomics

Author

Basyuni, Shadi, primary, Heskin, Laura, additional, Degasperi, Andrea, additional, Black, Daniella, additional, Koh, Gene Ching Chiek, additional, Chmelova, Lucia, additional, Rinaldi, Giuseppe, additional, Bell, Steven, additional, Grybowicz, Louise, additional, Elgar, Greg, additional, Memari, Yasin, additional, Robbe, Pauline, additional, Kingsbury, Zoya, additional, Caldas, Carlos, additional, Abraham, Jean, additional, Schuh, Anna, additional, Jones, J. Louise, additional, Group, PARTNER Trial, additional, Group, Personalised Breast Cancer Program, additional, Tischkowitz, Marc, additional, Brown, Matthew, additional, Davies, Helen, additional, and Nik-Zainal, Serena, additional

Published
2023
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14. 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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15. Author Correction: A practical framework and online tool for mutational signature analyses show intertissue variation and driver dependencies

Author

Degasperi, Andrea, Amarante, Tauanne Dias, Czarnecki, Jan, Shooter, Scott, Zou, Xueqing, Glodzik, Dominik, Morganella, Sandro, Nanda, Arjun S., Badja, Cherif, Koh, Gene, Momen, Sophie E., Georgakopoulos-Soares, Ilias, Dias, João M. L., Young, Jamie, Memari, Yasin, Davies, Helen, and Nik-Zainal, Serena

Published
2020
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17. Substitution mutational signatures in whole-genome-sequenced cancers in the UK population

Author

Degasperi, Andrea, Zou, Xueqing, Amarante, Tauanne Dias, Martinez-Martinez, Andrea, Koh, Gene Ching Chiek, Dias, João ML, Heskin, Laura, Chmelova, Lucia, Rinaldi, Giuseppe, Wang, Valerie Ya Wen, Nanda, Arjun S, Bernstein, Aaron, Momen, Sophie E, Young, Jamie, Perez-Gil, Daniel, Memari, Yasin, Badja, Cherif, Shooter, Scott, Czarnecki, Jan, Brown, Matthew A, Davies, Helen R, Genomics England Research Consortium, Nik-Zainal, Serena, Degasperi, Andrea [0000-0001-6879-0596], Nik-Zainal, Serena [0000-0001-5054-1727], and Apollo - University of Cambridge Repository

Subjects
Cohort Studies, Base Sequence, Neoplasms, DNA Mutational Analysis, Mutation, Population, Humans, United Kingdom
Abstract

Whole-genome sequencing (WGS) permits comprehensive cancer genome analyses, revealing mutational signatures, imprints of DNA damage and repair processes that have arisen in each patient's cancer. We performed mutational signature analyses on 12,222 WGS tumor-normal matched pairs, from patients recruited via the UK National Health Service. We contrasted our results to two independent cancer WGS datasets, the International Cancer Genome Consortium (ICGC) and Hartwig Foundation, involving 18,640 WGS cancers in total. Our analyses add 40 single and 18 double substitution signatures to the current mutational signature tally. Critically, we show for each organ, that cancers have a limited number of 'common' signatures and a long tail of 'rare' signatures. We provide a practical solution for utilizing this concept of common versus rare signatures in future analyses.

Published
2022

18. Abstract 805: RECAP (REpair CAPacity) identifies a subset of breast cancers unable to form RAD51 foci which are undetected by DNA-based BRCAness tests

Author

Meijer, Titia G., primary, Nguyen, Luan, additional, van Hoeck, Arne, additional, Ladan, Marjolijn M., additional, Verkaik, Nicole S., additional, Ruigrok-Ritstier, Kirsten, additional, van Deurzen, Carolien H., additional, van de Werken, Harmen J., additional, Lips, Esther H., additional, Linn, Sabine C., additional, Memari, Yasin, additional, Davies, Helen, additional, Nik-Zainal, Serena, additional, Kanaar, Roland, additional, Martens, John W., additional, Cuppen, Edwin, additional, Jager, Agnes, additional, and van Gent, Dik C., additional

Published
2022
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20. The UK10K project identifies rare variants in health and disease

Author

Walter, Klaudia, Min, Josine L., Huang, Jie, Crooks, Lucy, Memari, Yasin, Perry, John R. B., Xu, ChangJiang, Futema, Marta, Lawson, Daniel, Iotchkova, Valentina, Schiffels, Stephan, Hendricks, Audrey E., Danecek, Petr, Li, Rui, Floyd, James, Wain, Louise V., Humphries, Steve E., Barrett, Jeffrey C., Bala, Senduran, Clapham, Peter, Coates, Guy, Cox, Tony, Daly, Allan, Du, Yuanping, Edkins, Sarah, Ellis, Peter, Flicek, Paul, Guo, Xiaosen, Guo, Xueqin, Huang, Liren, Jackson, David K., Joyce, Chris, Keane, Thomas, Kolb-Kokocinski, Anja, Langford, Cordelia, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Maslen, John, McCarthy, Shane, (co-chair), Muddyman, Dawn, Quail, Michael A., Stalker, Jim, (co-chair), Sun, Jianping, Tian, Jing, Wang, Guangbiao, Wang, Jun, Wang, Yu, Wong, Kim, Zhang, Pingbo, Birney, Ewan, Boustred, Chris, Chen, Lu, Clement, Gail, Cocca, Massimiliano, Smith, George Davey, Day, Ian N. M., Day-Williams, Aaron, Down, Thomas, Dunham, Ian, Evans, David M., Gaunt, Tom R., Geihs, Matthias, Hart, Deborah, Howie, Bryan, Hubbard, Tim, Hysi, Pirro, Jamshidi, Yalda, Karczewski, Konrad J., Kemp, John P., Lachance, Genevieve, Lek, Monkol, Lopes, Margarida, MacArthur, Daniel G., Marchini, Jonathan, Mangino, Massimo, Mathieson, Iain, Metrustry, Sarah, Moayyeri, Alireza, Northstone, Kate, Panoutsopoulou, Kalliope, Paternoster, Lavinia, Quaye, Lydia, Richards, Brent J., (co-chair), Ring, Susan, Ritchie, Graham R. S., Shihab, Hashem A., Shin, So-Youn, Small, Kerrin S., Artigas, María Soler, Soranzo, Nicole, (co-chair), Southam, Lorraine, Spector, Timothy D., St Pourcain, Beate, Surdulescu, Gabriela, Tachmazidou, Ioanna, Timpson, Nicholas J., (co-chair), Tobin, Martin D., Valdes, Ana M., Visscher, Peter M., Ward, Kirsten, Wilson, Scott G., Yang, Jian, Zhang, Feng, Zheng, Hou-Feng, Anney, Richard, Ayub, Muhammad, Blackwood, Douglas, Bolton, Patrick F., Breen, Gerome, Collier, David A., Craddock, Nick, Curran, Sarah, Curtis, David, Gallagher, Louise, Geschwind, Daniel, Gurling, Hugh, Holmans, Peter, Lee, Irene, Lönnqvist, Jouko, McGuffin, Peter, McIntosh, Andrew M., McKechanie, Andrew G., McQuillin, Andrew, Morris, James, OʼDonovan, Michael C., Owen, Michael J., (co-chair), Palotie, Aarno, (co-chair), Parr, Jeremy R., Paunio, Tiina, Pietilainen, Olli, Rehnström, Karola, Sharp, Sally I., Skuse, David, St Clair, David, Suvisaari, Jaana, Walters, James T. R., Williams, Hywel J., Barroso, Inês, (co-chair), Bochukova, Elena, Bounds, Rebecca, Dominiczak, Anna, Farooqi, Sadaf I., (co-chair), Keogh, Julia, Marenne, Gaëlle, Morris, Andrew, OʼRahilly, Stephen, Porteous, David J., Smith, Blair H., Wheeler, Eleanor, Al Turki, Saeed, Anderson, Carl A., Antony, Dinu, Beales, Phil, Bentham, Jamie, Bhattacharya, Shoumo, Calissano, Mattia, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Fitzpatrick, David R., (co-chair), Foley, Reghan A., Franklin, Christopher S., Grozeva, Detelina, Hurles, Matthew E., (co-chair), Mitchison, Hannah M., Muntoni, Francesco, Onoufriadis, Alexandros, Parker, Victoria, Payne, Felicity, Raymond, Lucy F., Roberts, Nicola, Savage, David B., Scambler, Peter, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert K., Serra, Eva, Spasic-Boskovic, Olivera, Stevens, Elizabeth, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Williamson, Kathleen A., Wilson, Crispian, Whyte, Tamieka, Ciampi, Antonio, Greenwood, Celia M. T., (co-chair), Oualkacha, Karim, Zeggini, Eleftheria, (co-chair), Bobrow, Martin, Griffin, Heather, Kaye, Jane, (co-chair), Kennedy, Karen, Kent, Alastair, Smee, Carol, Charlton, Ruth, Ekong, Rosemary, Khawaja, Farrah, Lopes, Luis R., Migone, Nicola, Payne, Stewart J., Plagnol, Vincent, (chair), Pollitt, Rebecca C., Povey, Sue, Ridout, Cheryl K., Robinson, Rachel L., Scott, Richard H., Shaw, Adam, Syrris, Petros, Taylor, Rohan, Vandersteen, Anthony M., Durbin, Richard, (chair), Amuzu, Antoinette, Casas, Juan Pablo, Chambers, John C., Dedoussis, George, Gambaro, Giovanni, Gasparini, Paolo, Isaacs, Aaron, Johnson, Jon, Kleber, Marcus E., Kooner, Jaspal S., Langenberg, Claudia, Luan, Jianʼan, Malerba, Giovanni, März, Winfried, Matchan, Angela, Morris, Richard, Nordestgaard, Børge G., Benn, Marianne, Scott, Robert A., Toniolo, Daniela, Traglia, Michela, Tybjaerg-Hansen, Anne, van Duijn, Cornelia M., van Leeuwen, Elisabeth M., Varbo, Anette, Whincup, Peter, Zaza, Gianluigi, and Zhang, Weihua

Published
2015
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21. Homozygous loss-of-function variants in European cosmopolitan and isolate populations

Author

Kaiser, Vera B., Svinti, Victoria, Prendergast, James G., Chau, You-Ying, Campbell, Archie, Patarcic, Inga, Barroso, Inês, Joshi, Peter K., Hastie, Nicholas D., Miljkovic, Ana, Taylor, Martin S., Enroth, Stefan, Memari, Yasin, Kolb-Kokocinski, Anja, Wright, Alan F., Gyllensten, Ulf, Durbin, Richard, Rudan, Igor, Campbell, Harry, Polašek, Ozren, Johansson, Åsa, Sauer, Sascha, Porteous, David J., Fraser, Ross M., Drake, Camilla, Vitart, Veronique, Hayward, Caroline, Semple, Colin A., and Wilson, James F.

Published
2015
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22. Immunofluorescence Analysis and Diagnosis of Primary Ciliary Dyskinesia with Radial Spoke Defects

Author

Frommer, Adrien, Hjeij, Rim, Loges, Niki T., Edelbusch, Christine, Jahnke, Charlotte, Raidt, Johanna, Werner, Claudius, Wallmeier, Julia, Groe-Onnebrink, Jörg, Olbrich, Heike, Cindrić, Sandra, Jaspers, Martine, Boon, Mieke, Memari, Yasin, Durbin, Richard, Kolb-Kokocinski, Anja, Sauer, Sascha, Marthin, June K., Nielsen, Kim G., Amirav, Israel, Elias, Nael, Kerem, Eitan, Shoseyov, David, Haeffner, Karsten, and Omran, Heymut

Published
2015
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23. Abstract 534: Functional drug screening of organoids from ovarian cancer patients demonstrates clinical and genomic concordance and identifies novel therapeutic vulnerabilities

Author

Lui, Goldie, primary, Richardson, Anne, additional, Chatterjee, Payel, additional, Pollastro, Madison, additional, Lints, Mia, additional, Peretti, Danielle, additional, Rosati, Rachele, additional, Appleyard, Lauren, additional, Durenberger, Grace, additional, Diaz, Robert, additional, Gurley, Kay, additional, Stork, Isabella, additional, Whitney, Adam, additional, Kapeli, Katannya, additional, Swan, Hallie, additional, Memari, Yasin, additional, Davies, Helen, additional, Nik-Zainal, Serena, additional, Banda, Kalyan, additional, Gray, Heidi, additional, Goff, Barbara, additional, Swisher, Elizabeth, additional, Margossian, Astrid, additional, Kemp, Christopher, additional, and Grandori, Carla, additional

Published
2021
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24. Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells

Author

Rouhani, Foad J, primary, Zou, Xueqing, additional, Danecek, Petr, additional, Dias Amarante, Tauanne, additional, Koh, Gene, additional, Wu, Qianxin, additional, Memari, Yasin, additional, Durbin, Richard, additional, Martincorena, Inigo, additional, Bassett, Andrew R, additional, Gaffney, Daniel, additional, and Nik-Zainal, Serena, additional

Published
2021
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25. Population-scale proteome variation in human induced pluripotent stem cells

Author

Mirauta, Bogdan Andrei, Seaton, Daniel D, Bensaddek, Dalila, Brenes, Alejandro, Bonder, Marc Jan, Kilpinen, Helena, Agu, Chukwuma A, Alderton, Alex, Danecek, Petr, Denton, Rachel, Durbin, Richard, Gaffney, Daniel J, Goncalves, Angela, Halai, Reena, Harper, Sarah, Kirton, Christopher M, Kolb-Kokocinski, Anja, Leha, Andreas, McCarthy, Shane A, Memari, Yasin, Patel, Minal, Birney, Ewan, Casale, Francesco Paolo, Clarke, Laura, Harrison, Peter W, Streeter, Ian, Denovi, Davide, Stegle, Oliver, Lamond, Angus I, Meleckyte, Ruta, Moens, Natalie, Watt, Fiona M, Ouwehand, Willem H, Beales, Philip, Mirauta, Bogdan Andrei [0000-0002-9733-292X], Bonder, Marc Jan [0000-0002-8431-3180], Kilpinen, Helena [0000-0001-6692-6154], Stegle, Oliver [0000-0002-8818-7193], Lamond, Angus I [0000-0001-6204-6045], Apollo - University of Cambridge Repository, and Helsinki Institute of Life Science HiLIFE

Subjects
Male, Proteomics, Proteome, Genome-wide association study, VARIANTS, Transcriptome, 0302 clinical medicine, SCHIZOPHRENIA, Human proteome project, genetics, Disease, Biology (General), Induced pluripotent stem cell, Child, GENE-EXPRESSION, 0303 health sciences, education.field_of_study, Drug discovery, General Neuroscience, General Medicine, Middle Aged, Phenotype, Child, Preschool, Medicine, ABUNDANCE, Female, Research Article, Adult, Adolescent, Genotype, QH301-705.5, induced pluripotent stem cells, Science, Population, Quantitative Trait Loci, deleterious variants, Genomics, Computational biology, Quantitative trait locus, Biology, General Biochemistry, Genetics and Molecular Biology, DIFFERENTIAL EXPRESSION, 03 medical and health sciences, Young Adult, RESOURCE, REVEALS, genomics, Humans, human, RNA, Messenger, education, 030304 developmental biology, Aged, IDENTIFICATION, General Immunology and Microbiology, Infant, Newborn, Genetic Variation, Infant, Genetics and Genomics, QUANTIFICATION, Genetics, Population, REGULATORY VARIATION, 3111 Biomedicine, 030217 neurology & neurosurgery
Abstract

Human disease phenotypes are driven primarily by alterations in protein expression and/or function. To date, relatively little is known about the variability of the human proteome in populations and how this relates to variability in mRNA expression and to disease loci. Here, we present the first comprehensive proteomic analysis of human induced pluripotent stem cells (iPSC), a key cell type for disease modelling, analysing 202 iPSC lines derived from 151 donors, with integrated transcriptome and genomic sequence data from the same lines. We characterised the major genetic and non-genetic determinants of proteome variation across iPSC lines and assessed key regulatory mechanisms affecting variation in protein abundance. We identified 654 protein quantitative trait loci (pQTLs) in iPSCs, including disease-linked variants in protein-coding sequences and variants with trans regulatory effects. These include pQTL linked to GWAS variants that cannot be detected at the mRNA level, highlighting the utility of dissecting pQTL at peptide level resolution.

Published
2020

26. Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression

Author

Cuomo, Anna S. E., Seaton, Daniel D., McCarthy, Davis J., Martinez, Iker, Bonder, Marc Jan, Garcia-Bernardo, Jose, Amatya, Shradha, Madrigal, Pedro, Isaacson, Abigail, Buettner, Florian, Knights, Andrew, Natarajan, Kedar Nath, Vallier, Ludovic, Marioni, John C., Chhatriwala, Mariya, Stegle, Oliver, Agu, Chukwuma A., Alderton, Alex, Danecek, Petr, Denton, Rachel, Durbin, Richard, Gaffney, Daniel J., Goncalves, Angela, Halai, Reena, Harper, Sarah, Kirton, Christopher M., Kolb-Kokocinski, Anja, Leha, Andreas, McCarthy, Shane A., Memari, Yasin, Patel, Minal, Birney, Ewan, Casale, Francesco Paolo, Clarke, Laura, Harrison, Peter W., Kilpinen, Helena, Streeter, Ian, Denovi, Davide, Meleckyte, Ruta, Moens, Natalie, Watt, Fiona M., Ouwehand, Willem H., Lamond, Angus I., Bensaddek, Dalila, Beales, Philip, Seaton, Daniel D. [0000-0002-5222-3893], McCarthy, Davis J. [0000-0002-2218-6833], Madrigal, Pedro [0000-0003-1959-8199], Knights, Andrew [0000-0003-2107-4175], Natarajan, Kedar Nath [0000-0002-9264-1280], Vallier, Ludovic [0000-0002-3848-2602], Marioni, John C. [0000-0001-9092-0852], and Apollo - University of Cambridge Repository

Subjects
13/31, 45/91, 631/532/2064/2158, 631/208/729/743, 45/43, article, 631/208/191, 631/208/205, 45/100, 45/15, 38/91
Abstract

Recent developments in stem cell biology have enabled the study of cell fate decisions in early human development that are impossible to study in vivo. However, understanding how development varies across individuals and, in particular, the influence of common genetic variants during this process has not been characterised. Here, we exploit human iPS cell lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing to study population variation of endoderm differentiation. We identify molecular markers that are predictive of differentiation efficiency of individual lines, and utilise heterogeneity in the genetic background across individuals to map hundreds of expression quantitative trait loci that influence expression dynamically during differentiation and across cellular contexts.

Published
2020

27. 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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28. Substantial somatic genomic variation and selection for BCORmutations in human induced pluripotent stem cells

Author

Rouhani, Foad J., Zou, Xueqing, Danecek, Petr, Badja, Cherif, Amarante, Tauanne Dias, Koh, Gene, Wu, Qianxin, Memari, Yasin, Durbin, Richard, Martincorena, Inigo, Bassett, Andrew R., Gaffney, Daniel, and Nik-Zainal, Serena

Abstract

We explored human induced pluripotent stem cells (hiPSCs) derived from different tissues to gain insights into genomic integrity at single-nucleotide resolution. We used genome sequencing data from two large hiPSC repositories involving 696 hiPSCs and daughter subclones. We find ultraviolet light (UV)-related damage in ~72% of skin fibroblast-derived hiPSCs (F-hiPSCs), occasionally resulting in substantial mutagenesis (up to 15 mutations per megabase). We demonstrate remarkable genomic heterogeneity between independent F-hiPSC clones derived during the same round of reprogramming due to oligoclonal fibroblast populations. In contrast, blood-derived hiPSCs (B-hiPSCs) had fewer mutations and no UV damage but a high prevalence of acquired BCORmutations (26.9% of lines). We reveal strong selection pressure for BCORmutations in F-hiPSCs and B-hiPSCs and provide evidence that they arise in vitro. Directed differentiation of hiPSCs and RNA sequencing showed that BCORmutations have functional consequences. Our work strongly suggests that detailed nucleotide-resolution characterization is essential before using hiPSCs.

Published
2022
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29. Seventy-five genetic loci influencing the human red blood cell

Author

van der Harst, Pim, Zhang, Weihua, Mateo Leach, Irene, Rendon, Augusto, Verweij, Niek, Sehmi, Joban, Paul, Dirk S., Elling, Ulrich, Allayee, Hooman, Li, Xinzhong, Radhakrishnan, Aparna, Tan, Sian-Tsung, Voss, Katrin, Weichenberger, Christian X., Albers, Cornelis A., Al-Hussani, Abtehale, Asselbergs, Folkert W., Ciullo, Marina, Danjou, Fabrice, Dina, Christian, Esko, Tõnu, Evans, David M., Franke, Lude, Gögele, Martin, Hartiala, Jaana, Hersch, Micha, Holm, Hilma, Hottenga, Jouke-Jan, Kanoni, Stavroula, Kleber, Marcus E., Lagou, Vasiliki, Langenberg, Claudia, Lopez, Lorna M., Lyytikäinen, Leo-Pekka, Melander, Olle, Murgia, Federico, Nolte, Ilja M., OʼReilly, Paul F., Padmanabhan, Sandosh, Parsa, Afshin, Pirastu, Nicola, Porcu, Eleonora, Portas, Laura, Prokopenko, Inga, Ried, Janina S., Shin, So-Youn, Tang, Clara S., Teumer, Alexander, Traglia, Michela, Ulivi, Sheila, Westra, Harm-Jan, Yang, Jian, Hua Zhao, Jing, Anni, Franco, Abdellaoui, Abdel, Attwood, Antony, Balkau, Beverley, Bandinelli, Stefania, Bastardot, François, Benyamin, Beben, Boehm, Bernhard O., Cookson, William O., Das, Debashish, de Bakker, Paul I. W., de Boer, Rudolf A., de Geus, Eco J. C., de Moor, Marleen H., Dimitriou, Maria, Domingues, Francisco S., Döring, Angela, Engström, Gunnar, Ingi Eyjolfsson, Gudmundur, Ferrucci, Luigi, Fischer, Krista, Galanello, Renzo, Garner, Stephen F., Genser, Bernd, Gibson, Quince D., Girotto, Giorgia, Fannar Gudbjartsson, Daniel, Harris, Sarah E., Hartikainen, Anna-Liisa, Hastie, Claire E., Hedblad, Bo, Illig, Thomas, Jolley, Jennifer, Kähönen, Mika, Kema, Ido P., Kemp, John P., Liang, Liming, Lloyd-Jones, Heather, Loos, Ruth J. F., Meacham, Stuart, Medland, Sarah E., Meisinger, Christa, Memari, Yasin, Mihailov, Evelin, Miller, Kathy, Moffatt, Miriam F., Nauck, Matthias, Novatchkova, Maria, Nutile, Teresa, Olafsson, Isleifur, Onundarson, Pall T., Parracciani, Debora, Penninx, Brenda W., Perseu, Lucia, Piga, Antonio, Pistis, Giorgio, Pouta, Anneli, Puc, Ursula, Raitakari, Olli, Ring, Susan M., Robino, Antonietta, Ruggiero, Daniela, Ruokonen, Aimo, Saint-Pierre, Aude, Sala, Cinzia, Salumets, Andres, Sambrook, Jennifer, Schepers, Hein, Oliver Schmidt, Carsten, Silljé, Herman H. W., Sladek, Rob, Smit, Johannes H., Starr, John M., Stephens, Jonathan, Sulem, Patrick, Tanaka, Toshiko, Thorsteinsdottir, Unnur, Tragante, Vinicius, van Gilst, Wiek H., Joost van Pelt, L., van Veldhuisen, Dirk J., Völker, Uwe, Whitfield, John B., Willemsen, Gonneke, Winkelmann, Bernhard R., Wirnsberger, Gerald, Algra, Ale, Cucca, Francesco, dʼAdamo, Adamo Pio, Danesh, John, Deary, Ian J., Dominiczak, Anna F., Elliott, Paul, Fortina, Paolo, Froguel, Philippe, Gasparini, Paolo, Greinacher, Andreas, Hazen, Stanley L., Jarvelin, Marjo-Riitta, Tee Khaw, Kay, Lehtimäki, Terho, Maerz, Winfried, Martin, Nicholas G., Metspalu, Andres, Mitchell, Braxton D., Montgomery, Grant W., Moore, Carmel, Navis, Gerjan, Pirastu, Mario, Pramstaller, Peter P., Ramirez-Solis, Ramiro, Schadt, Eric, Scott, James, Shuldiner, Alan R., Davey Smith, George, Gustav Smith, J., Snieder, Harold, Sorice, Rossella, Spector, Tim D., Stefansson, Kari, Stumvoll, Michael, Wilson Tang, W. H., Toniolo, Daniela, Tönjes, Anke, Visscher, Peter M., Vollenweider, Peter, Wareham, Nicholas J., Wolffenbuttel, Bruce H. R., Boomsma, Dorret I., Beckmann, Jacques S., Dedoussis, George V., Deloukas, Panos, Ferreira, Manuel A., Sanna, Serena, Uda, Manuela, Hicks, Andrew A., Martin Penninger, Josef, Gieger, Christian, Kooner, Jaspal S., Ouwehand, Willem H., Soranzo, Nicole, and Chambers, John C.

Published
2012
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30. New gene functions in megakaryopoiesis and platelet formation

Author

Gieger, Christian, Radhakrishnan, Aparna, Cvejic, Ana, Tang, Weihong, Porcu, Eleonora, Pistis, Giorgio, Serbanovic-Canic, Jovana, Elling, Ulrich, Goodall, Alison H., Labrune, Yann, Lopez, Lorna M., Mägi, Reedik, Meacham, Stuart, Okada, Yukinori, Pirastu, Nicola, Sorice, Rossella, Teumer, Alexander, Voss, Katrin, Zhang, Weihua, Ramirez-Solis, Ramiro, Bis, Joshua C., Ellinghaus, David, Gögele, Martin, Hottenga, Jouke-Jan, Langenberg, Claudia, Kovacs, Peter, O’Reilly, Paul F., Shin, So-Youn, Esko, Tõnu, Hartiala, Jaana, Kanoni, Stavroula, Murgia, Federico, Parsa, Afshin, Stephens, Jonathan, van der Harst, Pim, Ellen van der Schoot, C., Allayee, Hooman, Attwood, Antony, Balkau, Beverley, Bastardot, François, Basu, Saonli, Baumeister, Sebastian E., Biino, Ginevra, Bomba, Lorenzo, Bonnefond, Amélie, Cambien, François, Chambers, John C., Cucca, Francesco, D’Adamo, Pio, Davies, Gail, de Boer, Rudolf A., de Geus, Eco J. C., Döring, Angela, Elliott, Paul, Erdmann, Jeanette, Evans, David M., Falchi, Mario, Feng, Wei, Folsom, Aaron R., Frazer, Ian H., Gibson, Quince D., Glazer, Nicole L., Hammond, Chris, Hartikainen, Anna-Liisa, Heckbert, Susan R., Hengstenberg, Christian, Hersch, Micha, Illig, Thomas, Loos, Ruth J. F., Jolley, Jennifer, Tee Khaw, Kay, Kühnel, Brigitte, Kyrtsonis, Marie-Christine, Lagou, Vasiliki, Lloyd-Jones, Heather, Lumley, Thomas, Mangino, Massimo, Maschio, Andrea, Mateo Leach, Irene, McKnight, Barbara, Memari, Yasin, Mitchell, Braxton D., Montgomery, Grant W., Nakamura, Yusuke, Nauck, Matthias, Navis, Gerjan, Nöthlings, Ute, Nolte, Ilja M., Porteous, David J., Pouta, Anneli, Pramstaller, Peter P., Pullat, Janne, Ring, Susan M., Rotter, Jerome I., Ruggiero, Daniela, Ruokonen, Aimo, Sala, Cinzia, Samani, Nilesh J., Sambrook, Jennifer, Schlessinger, David, Schreiber, Stefan, Schunkert, Heribert, Scott, James, Smith, Nicholas L., Snieder, Harold, Starr, John M., Stumvoll, Michael, Takahashi, Atsushi, Tang, Wilson W.H., Taylor, Kent, Tenesa, Albert, Lay Thein, Swee, Tönjes, Anke, Uda, Manuela, Ulivi, Sheila, van Veldhuisen, Dirk J., Visscher, Peter M., Völker, Uwe, Wichmann, Erich H., Wiggins, Kerri L., Willemsen, Gonneke, Yang, Tsun-Po, Hua Zhao, Jing, Zitting, Paavo, Bradley, John R., Dedoussis, George V., Gasparini, Paolo, Hazen, Stanley L., Metspalu, Andres, Pirastu, Mario, Shuldiner, Alan R., Joost van Pelt, L., Zwaginga, Jaap-Jan, Boomsma, Dorret I., Deary, Ian J., Franke, Andre, Froguel, Philippe, Ganesh, Santhi K., Jarvelin, Marjo-Riitta, Martin, Nicholas G., Meisinger, Christa, Psaty, Bruce M., Spector, Timothy D., Wareham, Nicholas J., Akkerman, Jan-Willem N., Ciullo, Marina, Deloukas, Panos, Greinacher, Andreas, Jupe, Steve, Kamatani, Naoyuki, Khadake, Jyoti, Kooner, Jaspal S., Penninger, Josef, Prokopenko, Inga, Stemple, Derek, Toniolo, Daniela, Wernisch, Lorenz, Sanna, Serena, Hicks, Andrew A., Rendon, Augusto, Ferreira, Manuel A., Ouwehand, Willem H., and Soranzo, Nicole

Published
2011
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32. 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

33. Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis

Author

Yang, Yongjie, van der Klaauw, Agatha A., Zhu, Liangru, Cacciottolo, Tessa M., He, Yanlin, Stadler, Lukas K. J., Wang, Chunmei, Xu, Pingwen, Saito, Kenji, Hinton, Antentor, Yan, Xiaofeng, Keogh, Julia M., Henning, Elana, Banton, Matthew C., Hendricks, Audrey E., Bochukova, Elena G., Mistry, Vanisha, Lawler, Katherine L., Liao, Lan, Xu, Jianming, O'Rahilly, Stephen, Tong, Qingchun, Barroso, Ines, O'Malley, Bert W., Farooqi, I. Sadaf, Xu, Yong, Balasubramanian, Senduran, Clapham, Peter, Coates, Guy, Cox, Tony, Daly, Allan, Danecek, Petr, Du, Yuanping, Durbin, Richard, Edkins, Sarah, Ellis, Peter, Flicek, Paul, Guo, Xiaosen, Guo, Xueqin, Huang, Liren, Jackson, David K., Joyce, Chris, Keane, Thomas, Kolb-Kokocinski, Anja, Langford, Cordelia, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Maslen, John, McCarthy, Shane, Muddyman, Dawn, Quail, Michael A., Stalker, Jim, Sun, Jianping, Tian, Jing, Wang, Guangbiao, Wang, Jun, Wang, Yu, Wong, Kim, Zhang, Pingbo, Birney, Ewan, Boustred, Chris, Brion, Marie-Jo, Chen, Lu, Clement, Gail, Smith, George Davey, Day, Ian N. M., Day-Williams, Aaron, Down, Thomas, Dunham, Ian, Evans, David M., Fatemifar, Ghazaleh, Gaunt, Tom R., Geihs, Matthias, Greenwood, Celia M. T., Hart, Deborah, Howie, Bryan, Huang, Jie, Hubbard, Tim, Hysi, Pirro, Iotchkova, Valentina, Jamshidi, Yalda, Kemp, John P., Lachance, Genevieve, Lawson, Daniel, Lek, Monkol, Lopes, Margarida, MacArthur, Daniel G., Marchini, Jonathan, Massimo, Mangino, Mathieson, Iain, Memari, Yasin, Metrustry, Sarah, Min, Josine L., Moayyeri, Alireza, Northstone, Kate, Panoutsopoulou, Kalliope, Paternoster, Lavinia, Perry, John R. B., Quaye, Lydia, Richards, J. Brent, Ring, Susan, Ritchie, Graham R. S., Schiffels, Stephan, Shihab, Hashem A., Shin, So-Youn, Small, Kerrin S., Artigas, Maria Soler, Soranzo, Nicole, Southam, Lorraine, Spector, Timothy D., St Pourcain, Beate, Surdulescu, Gabriela, Tachmazidou, Ioanna, Timpson, Nicholas J., Tobin, Martin D., Valdes, Ana M., Visscher, Peter M., Wain, Louise V., Walter, Klaudia, Ward, Kirsten, Wilson, Scott G., Yang, Jian, Zeggini, Eleftheria, Zhang, Feng, Zheng, Hou-Feng, Anney, Richard, Ayub, Muhammad, Barrett, Jeffrey C., Blackwood, Douglas, Bolton, Patrick F., Breen, Gerome, Collier, David A., Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Gallagher, Louise, Geschwind, Daniel, Gurling, Hugh, Holmans, Peter, Lee, Irene, Lonnqvist, Jouko, McGuffin, Peter, McIntosh, Andrew M., McKechanie, Andrew G., McQuillin, Andrew, Morris, James, O'Donovan, Michael C., Owen, Michael J., Palotie, Aarno, Parr, Jeremy R., Paunio, Tiina, Pietilainen, Olli, Rehnstrom, Karola, Sharp, Sally I., Skuse, David, St Clair, David, Suvisaari, Jaana, Walters, James T. R., Williams, Hywel J., Bochukova, Elena, Bounds, Rebecca, Dominiczak, Anna, Keogh, Julia, Marenne, Gaelle, Morris, Andrew, Porteous, David J., Smith, Blair H., Wheeler, Eleanor, Al Turki, Saeed, Anderson, Carl A., Antony, Dinu, Beales, Phil, Bentham, Jamie, Bhattacharya, Shoumo, Calissano, Mattia, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Fitzpatrick, David R., Floyd, James, Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Grozeva, Detelina, Humphries, Steve E., Hurles, Matthew E., Mitchison, Hannah M., Muntoni, Francesco, Onoufriadis, Alexandros, Parker, Victoria, Payne, Felicity, Plagnol, Vincent, Raymond, F. Lucy, Roberts, Nicola, Savage, David B., Scambler, Peter, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert K., Serra, Eva, Spasic-Boskovic, Olivera, Stevens, Elizabeth, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Williamson, Kathleen A., Wilson, Crispian, Whyte, Tamieka, Ciampi, Antonio, Li, Rui, Oualkacha, Karim, Xu, ChangJiang, Bobrow, Martin, Griffin, Heather, Kaye, Jane, Kennedy, Karen, Kent, Alastair, Smee, Carol, Charlton, Ruth, Ekong, Rosemary, Khawaja, Farrah, Lopes, Luis R., Migone, Nicola, Payne, Stewart J., Pollitt, Rebecca C., Povey, Sue, Ridout, Cheryl K., Robinson, Rachel L., Scott, Richard H., Shaw, Adam, Syrris, Petros, Taylor, Rohan, Vandersteen, Anthony M., Amuzu, Antoinette, Casas, Juan Pablo, Chambers, John C., Cocca, Massimiliano, Dedoussis, George, Gambaro, Giovanni, Gasparini, Paolo, Isaacs, Aaron, Johnson, Jon, Kleber, Marcus E., Kooner, Jaspal S., Langenberg, Claudia, Luan, Jian'an, Malerba, Giovanni, Marz, Winfried, Matchan, Angela, Morris, Richard, Nordestgaard, Børge G., Benn, Marianne, Scott, Robert A., Toniolo, Daniela, Traglia, Michela, Tybjaerg-Hansen, Anne, van Duijn, Cornelia M., van Leeuwen, Elisabeth M., Varbo, Anette, Whincup, Peter, Zaza, Gianluigi, and Zhang, Weihua

Published
2019

34. The UK10K project identifies rare variants in health and disease

Author

UK10K Consortium, Walter, Klaudia, Min, Josine L, Huang, Jie, Crooks, Lucy, Memari, Yasin, McCarthy, Shane, Perry, John RB, Xu, ChangJiang, Futema, Marta, Lawson, Daniel, Iotchkova, Valentina, Schiffels, Stephan, Hendricks, Audrey E, Danecek, Petr, Li, Rui, Floyd, James, Wain, Louise V, Barroso, Inês, Humphries, Steve E, Hurles, Matthew E, Zeggini, Eleftheria, Barrett, Jeffrey C, Plagnol, Vincent, Richards, J Brent, Greenwood, Celia MT, Timpson, Nicholas J, Durbin, Richard, Soranzo, Nicole, McCarthy, Shane [0000-0002-2715-4187], Durbin, Richard [0000-0002-9130-1006], and Apollo - University of Cambridge Repository

Subjects
Male, Genome, Human, Genetics, Medical, Genetic Variation, Molecular Sequence Annotation, Genomics, Sequence Analysis, DNA, Reference Standards, Lipid Metabolism, United Kingdom, Cohort Studies, Genetics, Population, Receptors, LDL, Health, Humans, Disease, Exome, Female, Genetic Predisposition to Disease, Adiponectin, Alleles, Triglycerides, Genome-Wide Association Study
Abstract

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.

Published
2018
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35. An interactive genome browser of association results from the UK10K cohorts project

Author

Geihs, Matthias, Yan, Ying, Walter, Klaudia, Huang, Jie, Memari, Yasin, Min, Josine L, Mead, Daniel, UK10K Consortium, Hubbard, Tim J, Timpson, Nicholas J, Down, Thomas A, Soranzo, Nicole, Soranzo, Nicole [0000-0003-1095-3852], and Apollo - University of Cambridge Repository

Subjects
Genome, Human, Genetic Variation, High-Throughput Nucleotide Sequencing, Humans, natural sciences, Genetic Association Studies, Linkage Disequilibrium, Software
Abstract

UNLABELLED: High-throughput sequencing technologies survey genetic variation at genome scale and are increasingly used to study the contribution of rare and low-frequency genetic variants to human traits. As part of the Cohorts arm of the UK10K project, genetic variants called from low-read depth (average 7×) whole genome sequencing of 3621 cohort individuals were analysed for statistical associations with 64 different phenotypic traits of biomedical importance. Here, we describe a novel genome browser based on the Biodalliance platform developed to provide interactive access to the association results of the project. AVAILABILITY AND IMPLEMENTATION: The browser is available at http://www.uk10k.org/dalliance.html. Source code for the Biodalliance platform is available under a BSD license from http://github.com/dasmoth/dalliance, and for the LD-display plugin and backend from http://github.com/dasmoth/ldserv.

Published
2018
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36. Oral Abstracts 7: RA Clinical * O37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Author

Fleischmann, Roy, van Vollenhoven, Ronald F., Smolen, Josef, Emery, Paul, Florentinus, Stefan, Rathmann, Suchitrita, Kupper, Hartmut, Kavanaugh, Arthur, Taylor, Peter, Genovese, Mark, Keystone, Edward C., Drescher, Edit, Berclaz, Pierre-Yves, Lee, Chin, Fidelus-Gort, Rosalind, Schlichting, Douglas, Beattie, Scott, Luchi, Monica, Macias, William, Dikranian, Ara H., Alten, Rieke, Klearman, Micki, Musselman, David, Agarwal, Sunil, Green, Jennifer, Gabay, Cem, Weinblatt, Michael E., Schiff, Michael H., Valente, Robert, van der Heijde, Desiree, Citera, Gustavo, Zhao, Cathy, Maldonado, Michael A., Rakieh, Chadi, Nam, Jacqueline L., Hunt, Laura, Villeneuve, Edith, Bissell, Lesley-Anne, Das, Sudipto, Conaghan, Philip, McGonagle, Dennis, Wakefield, Richard J., Wright, Helen L., Thomas, Huw B., Moots, Robert, Edwards, Steven W., Hamann, Philip, Heward, James, McHugh, Neil, Lindsay, Mark A., Haroon, Muhammad, Giles, Jon T., Winchester, Robert, FitzGerald, Oliver, Karaderi, Tugce, Cohen, Carla J., Keidel, Sarah, Appleton, Louise H., Macfarlane, Gary J., Siebert, Stefan, Evans, David, Paul Wordsworth, B., Plant, Darren, Bowes, John, Orozco, Gisela, Morgan, Ann W., Wilson, Anthony G., Isaacs, John, Barton, Anne, Williams, Frances M., Livshits, Gregory, Spector, Tim, MacGregor, Alexander, Scollen, Serena, Cao, Dandan, Memari, Yasin, Hyde, Craig L., Zhang, Baohong, Sidders, Benjamin, Ziemek, Daniel, Shi, Yujian, Harris, Juliette, Harrow, Ian, Dougherty, Brian, Malarstig, Anders, McEwen, Robert, Stephens, Joel L., Patel, Ketan, Shin, So-Youn, Surdulescu, Gabriela, He, Wen, Jin, Xin, McMahon, Stephen B., Soranzo, Nicole, John, Sally, Wang, Jun, Spector, Tim D., Baker, Jonathan, Litherland, Gary J., Rowan, Andrew D., Kite, Kerry A., Bayley, Rachel, Yang, Peiming, Smith, Jacqueline P., Williams, Julie, Harper, Lorraine, Kitas, George D., Buckley, Christopher, Young, Stephen P., Fitzpatrick, Martin A., McGettrick, Helen M., Filer, Andrew, Raza, Karim, Nash, Gerard, Muthana, Munitta, Davies, Holly, Khetan, Sachin, Adeleke, Gbadebo, Hawtree, Sarah, Tazzyman, Simon, Morrow, Fiona, Ciani, Barbara, Wilson, Gerry, Quirke, Anne-Marie, Lugli, Elena, Wegner, Natalia, Charles, Peter, Hamilton, Bart, Chowdhury, Muslima, Ytterberg, Jimmy, Potempa, Jan, Fisher, Benjamin, Thiele, Geoffrey, Mikuls, Ted, Venables, Patrick, Adebajo, Adewale O., Mease, Philip, Gomez-Reino, Juan J., Wollenhaupt, Jurgen, Hu, ChiaChi, Stevens, Randall, Sieper, Joachim, Dougados, Maxime, Van den Bosch, Filip, Goupille, Philippe, Rathmann, Suchitrita S., Pangan, Aileen L., Maksymowych, Walter P., Brown, Matthew A., Elewaut, Dirk, Anderson, Jaclyn, Ramasamy, Pathma, O'Rourke, Michael, Murphy, Conor, Fitzgerald, Oliver, Jani, Meghna, Moore, Sarah, Mirjafari, Hoda, Macphie, Elizabeth, Chinoy, Hector, Rao, Chan, McLoughlin, Yokemei, and Preeti, Shah

Subjects
medicine.medical_specialty, Rheumatology, business.industry, Radiography, medicine, Pharmacology (medical), Inflammation, In patient, Radiology, medicine.symptom, Axial spondyloarthritis, business, Joint (geology)
Abstract

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (

Published
2013

37. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

Author

Zheng, Hou-Feng, Forgetta, Vincenzo, Hsu, Yi-Hsiang, Estrada, Karol, Rosello-Diez, Alberto, Leo, Paul J, Dahia, Chitra L, Park-Min, Kyung Hyun, Tobias, Jonathan H, Kooperberg, Charles, Kleinman, Aaron, Styrkarsdottir, Unnur, Liu, Ching-Ti, Uggla, Charlotta, Evans, Daniel S, Nielson, Carrie M, Walter, Klaudia, Pettersson-Kymmer, Ulrika, McCarthy, Shane, Eriksson, Joel, Kwan, Tony, Jhamai, Mila, Trajanoska, Katerina, Memari, Yasin, Min, Josine, Huang, Jie, Danecek, Petr, Wilmot, Beth, Li, Rui, Chou, Wen-Chi, Mokry, Lauren E, Moayyeri, Alireza, Claussnitzer, Melina, Cheng, Chia-Ho, Cheung, Warren, Medina-Gómez, Carolina, Ge, Bing, Chen, Shu-Huang, Choi, Kwangbom, Oei, Ling, Fraser, James, Kraaij, Robert, Hibbs, Matthew A, Gregson, Celia L, Paquette, Denis, Hofman, Albert, Wibom, Carl, Tranah, Gregory J, Marshall, Mhairi, Gardiner, Brooke B, Cremin, Katie, Auer, Paul, Hsu, Li, Ring, Sue, Tung, Joyce Y, Thorleifsson, Gudmar, Enneman, Anke W, van Schoor, Natasja M, de Groot, Lisette CPGM, van der Velde, Nathalie, Melin, Beatrice, Kemp, John P, Christiansen, Claus, Sayers, Adrian, Zhou, Yanhua, Calderari, Sophie, van Rooij, Jeroen, Carlson, Chris, Peters, Ulrike, Berlivet, Soizik, Dostie, Josée, Uitterlinden, Andre G, Williams, Stephen R, Farber, Charles, Grinberg, Daniel, LaCroix, Andrea Z, Haessler, Jeff, Chasman, Daniel I, Giulianini, Franco, Rose, Lynda M, Ridker, Paul M, Eisman, John A, Nguyen, Tuan V, Center, Jacqueline R, Nogues, Xavier, Garcia-Giralt, Natalia, Launer, Lenore L, Gudnason, Vilmunder, Mellström, Dan, Vandenput, Liesbeth, Amin, Najaf, van Duijn, Cornelia M, Karlsson, Magnus K, Ljunggren, Östen, Svensson, Olle, Hallmans, Göran, Rousseau, François, Giroux, Sylvie, Bussière, Johanne, Arp, Pascal P, Koromani, Fjorda, Prince, Richard L, Lewis, Joshua R, Langdahl, Bente L, Hermann, A Pernille, Jensen, Jens-Erik B, Kaptoge, Stephen, Khaw, Kay-Tee, Reeve, Jonathan, Formosa, Melissa M, Xuereb-Anastasi, Angela, Åkesson, Kristina, McGuigan, Fiona E, Garg, Gaurav, Olmos, Jose M, Zarrabeitia, Maria T, Riancho, Jose A, Ralston, Stuart H, Alonso, Nerea, Jiang, Xi, Goltzman, David, Pastinen, Tomi, Grundberg, Elin, Gauguier, Dominique, Orwoll, Eric S, Karasik, David, Davey-Smith, George, AOGC Consortium, Smith, Albert V, Siggeirsdottir, Kristin, Harris, Tamara B, Zillikens, M Carola, van Meurs, Joyce BJ, Thorsteinsdottir, Unnur, Maurano, Matthew T, Timpson, Nicholas J, Soranzo, Nicole, Durbin, Richard, Wilson, Scott G, Ntzani, Evangelia E, Brown, Matthew A, Stefansson, Kari, Hinds, David A, Spector, Tim, Cupples, L Adrienne, Ohlsson, Claes, Greenwood, Celia MT, UK10K Consortium, Jackson, Rebecca D, Rowe, David W, Loomis, Cynthia A, Evans, David M, Ackert-Bicknell, Cheryl L, Joyner, Alexandra L, Duncan, Emma L, Kiel, Douglas P, Rivadeneira, Fernando, and Richards, J Brent

Subjects
Homeodomain Proteins, Genotype, Genome, Human, General Science & Technology, European Continental Ancestry Group, Genetic Variation, Sequence Analysis, DNA, Genomics, Bone and Bones, Europe, Wnt Proteins, Mice, Disease Models, Animal, Fractures, Bone, AOGC Consortium, Gene Frequency, Bone Density, MD Multidisciplinary, UK10K Consortium, Animals, Humans, Genetic Predisposition to Disease, Female, Exome
Abstract

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Published
2015

38. 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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39. Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits

Author

Tachmazidou, Ioanna, primary, Süveges, Dániel, additional, Min, Josine L., additional, Ritchie, Graham R.S., additional, Steinberg, Julia, additional, Walter, Klaudia, additional, Iotchkova, Valentina, additional, Schwartzentruber, Jeremy, additional, Huang, Jie, additional, Memari, Yasin, additional, McCarthy, Shane, additional, Crawford, Andrew A., additional, Bombieri, Cristina, additional, Cocca, Massimiliano, additional, Farmaki, Aliki-Eleni, additional, Gaunt, Tom R., additional, Jousilahti, Pekka, additional, Kooijman, Marjolein N., additional, Lehne, Benjamin, additional, Malerba, Giovanni, additional, Männistö, Satu, additional, Matchan, Angela, additional, Medina-Gomez, Carolina, additional, Metrustry, Sarah J., additional, Nag, Abhishek, additional, Ntalla, Ioanna, additional, Paternoster, Lavinia, additional, Rayner, Nigel W., additional, Sala, Cinzia, additional, Scott, William R., additional, Shihab, Hashem A., additional, Southam, Lorraine, additional, St Pourcain, Beate, additional, Traglia, Michela, additional, Trajanoska, Katerina, additional, Zaza, Gialuigi, additional, Zhang, Weihua, additional, Artigas, María S., additional, Bansal, Narinder, additional, Benn, Marianne, additional, Chen, Zhongsheng, additional, Danecek, Petr, additional, Lin, Wei-Yu, additional, Locke, Adam, additional, Luan, Jian’an, additional, Manning, Alisa K., additional, Mulas, Antonella, additional, Sidore, Carlo, additional, Tybjaerg-Hansen, Anne, additional, Varbo, Anette, additional, Zoledziewska, Magdalena, additional, Finan, Chris, additional, Hatzikotoulas, Konstantinos, additional, Hendricks, Audrey E., additional, Kemp, John P., additional, Moayyeri, Alireza, additional, Panoutsopoulou, Kalliope, additional, Szpak, Michal, additional, Wilson, Scott G., additional, Boehnke, Michael, additional, Cucca, Francesco, additional, Di Angelantonio, Emanuele, additional, Langenberg, Claudia, additional, Lindgren, Cecilia, additional, McCarthy, Mark I., additional, Morris, Andrew P., additional, Nordestgaard, Børge G., additional, Scott, Robert A., additional, Tobin, Martin D., additional, Wareham, Nicholas J., additional, Burton, Paul, additional, Chambers, John C., additional, Smith, George Davey, additional, Dedoussis, George, additional, Felix, Janine F., additional, Franco, Oscar H., additional, Gambaro, Giovanni, additional, Gasparini, Paolo, additional, Hammond, Christopher J., additional, Hofman, Albert, additional, Jaddoe, Vincent W.V., additional, Kleber, Marcus, additional, Kooner, Jaspal S., additional, Perola, Markus, additional, Relton, Caroline, additional, Ring, Susan M., additional, Rivadeneira, Fernando, additional, Salomaa, Veikko, additional, Spector, Timothy D., additional, Stegle, Oliver, additional, Toniolo, Daniela, additional, Uitterlinden, André G., additional, Barroso, Inês, additional, Greenwood, Celia M.T., additional, Perry, John R.B., additional, Walker, Brian R., additional, Butterworth, Adam S., additional, Xue, Yali, additional, Durbin, Richard, additional, Small, Kerrin S., additional, Soranzo, Nicole, additional, Timpson, Nicholas J., additional, and Zeggini, Eleftheria, additional

Published
2017
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40. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Author

Huang, Jie, Howie, Bryan, McCarthy, Shane, Memari, Yasin, Walter, Klaudia, Min, Josine L, Danecek, Petr, Malerba, Giovanni, Trabetti, Elisabetta, Zheng, Hou-Feng, UK10K Consortium, Gambaro, Giovanni, Richards, J Brent, Durbin, Richard, Timpson, Nicholas J, Marchini, Jonathan, Soranzo, Nicole, Durbin, Richard [0000-0002-9130-1006], Marchini, Jonathan [0000-0003-0610-8322], Soranzo, Nicole [0000-0003-1095-3852], and Apollo - University of Cambridge Repository

Subjects
Adult, Aged, 80 and over, Models, Statistical, Adolescent, Genotype, Models, Genetic, Genome, Human, Genetic Variation, Middle Aged, Polymorphism, Single Nucleotide, United Kingdom, White People, Young Adult, Gene Frequency, Haplotypes, Italy, Humans, Alleles, Aged
Abstract

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants.

Published
2015

41. Erratum: Whole-genome sequence-based analysis of thyroid function

Author

Taylor, Peter N, Porcu, Eleonora, Chew, Shelby, Campbell, Purdey J, Traglia, Michela, Brown, Suzanne J, Mullin, Benjamin H, Shihab, Hashem A, Min, Josine, Walter, Klaudia, Memari, Yasin, Huang, Jie, Barnes, Michael R, Beilby, John P, Charoen, Pimphen, Danecek, Petr, Dudbridge, Frank, Forgetta, Vincenzo, Greenwood, Celia, Grundberg, Elin, Johnson, Andrew D, Hui, Jennie, Lim, Ee M, McCarthy, Shane, Muddyman, Dawn, Panicker, Vijay, Perry, John RB, Bell, Jordana T, Yuan, Wei, Relton, Caroline, Gaunt, Tom, Schlessinger, David, Abecasis, Goncalo, Cucca, Francesco, Surdulescu, Gabriela L, Woltersdorf, Wolfram, Zeggini, Eleftheria, Zheng, Hou-Feng, Toniolo, Daniela, Dayan, Colin M, Naitza, Silvia, Walsh, John P, Spector, Tim, Smith, George Davey, Durbin, Richard, Richards, J Brent, Sanna, Serena, Soranzo, Nicole, Timpson, Nicholas J, Wilson, Scott G, and UK10K Consortium

Published
2015

42. Erratum: A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans

Author

Timpson, Nicholas J., Walter, Klaudia, Min, Josine L., Tachmazidou, Ioanna, Malerba, Giovanni, Shin, So-Youn, Chen, Lu, Futema, Marta, Southam, Lorraine, Iotchkova, Valentina, Cocca, Massimiliano, Huang, Jie, Memari, Yasin, McCarthy, Shane, Danecek, Petr, Muddyman, Dawn, Mangino, Massimo, Menni, Cristina, Perry, John R. B., Ring, Susan M., Gaye, Amadou, Dedoussis, George, Farmaki, Aliki-Eleni, Burton, Paul, Talmud, Philippa J., Gambaro, Giovanni, Spector, Tim D., Smith, George Davey, Durbin, Richard, Richards, J. Brent, Humphries, Steve E., Zeggini, Eleftheria, and Soranzo, Nicole

Subjects
Male, Apolipoprotein C-III, Multidisciplinary, Polymorphism, Genetic, Twins, General Physics and Astronomy, General Chemistry, Lipoproteins, VLDL, Middle Aged, General Biochemistry, Genetics and Molecular Biology, White People, Alternative Splicing, Gene Frequency, Humans, Female, Erratum, Child, Lipoproteins, HDL, Alleles, Triglycerides
Abstract

The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (-1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10(-8))) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (-1.0 s.d. (s.e.=0.173), P-value=7.32 × 10(-9)). This is consistent with an effect between 0.5 and 1.5 mmol l(-1) dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale.

Published
2015

43. Homozygous loss-of-function variants in European cosmopolitan and isolate populations

Author

Kaiser, Vera B, Svinti, Victoria, Prendergast, James G, Chau, You-Ying, Campbell, Archie, Patarcic, Inga, Barroso, Inês, Joshi, Peter K, Hastie, Nicholas D, Miljkovic, Ana, Taylor, Martin S, Scotland, Generation, Enroth, Stefan, Memari, Yasin, Kolb-Kokocinski, Anja, Wright, Alan F, Gyllensten, Ulf, Durbin, Richard, Rudan, Igor, Campbell, Harry, Polašek, Ozren, Johansson, Åsa, Sauer, Sascha, Porteous, David J, Fraser, Ross M, Drake, Camilla, Vitart, Veronique, Hayward, Caroline, Semple, Colin A, and Wilson, James F

Subjects
Medical Genetics, Medicinsk genetik
Abstract

Homozygous Loss of Function (HLOF) variants provide a valuable window on gene function in humans, as well as an inventory of the human genes that are not essential for survival and reproduction. All humans carry at least a few HLOF variants, but the exact number of inactivated genes that can be tolerated is currently unknown - as are the phenotypic effects of losing function for most human genes. Here, we make use of 1,432 whole exome sequences from five European populations to expand the catalogue of known human HLOF mutations; after stringent filtering of variants in our dataset, we identify a total of 173 HLOF mutations, 76 (44%) of which have not been observed previously. We find that population isolates are particularly well suited to surveys of novel HLOF genes because individuals in such populations carry extensive runs of homozygosity, which we show are enriched for novel, rare HLOF variants. Further, we make use of extensive phenotypic data to show that most HLOFs, ascertained in population-based samples, appear to have little detectable effect on the phenotype. On the contrary, we document several genes directly implicated in disease that seem to tolerate HLOF variants. Overall HLOF genes are enriched for olfactory receptor function and are expressed in testes more often than expected, consistent with reduced purifying selection and incipient pseudogenisation.

Published
2015

44. A large-scale whole genome sequence-based analysis discovered novel genetic variants influencing bone mineral density: Results from the GEFOS and UK10K Consortia

Author

Zheng, Hou-Feng, Forgetta, Vince, Hsu, Yi-Hsiang, Estrada, Karol, Leo, Paul, Tobias, Jonathan, Kooperberg, Charles, Liu, Ching-Ti, Rosello-Diez, Alberto, Evans, Daniel, Nielson, Carrie, Pettersson-Kymmer, Ulrika, Eriksson, Joel, Kwan, Tony, Walter, Klaudia, Memari, Yasin, Mccarthy, Shane, Min, Josine, Huang, Jie, Danecek, Petr, Wilmot, Beth, Li, Rui, Chou, Wen-Chi, Mokry, Lauren, Moayyeri, Alireza, Claussnitzer, Melina, Cheng, Chia-Ho, Cheung, Warren, Medina-Gomez, Carolina, Ge, Bing, Chen, Shu-Huang, Choi, Kwangbom, Oei, Ling, Fraser, James, Kraaij, Robert, Hibbs, Matthew, Gregson, Celia, Paquette, Denis, Hofman, Albert, Wibom, Carl, Marshall, Mhairi, Gardiner, Brooke, Auer, Paul, Hsu, Li, Ring, Sue, Velde, Nathalie, Melin, Beatrice, Kemp, John, Sayers, Adrian, Zhou, Yanhua, Calderari, Sophie, Maurano, Matthew, Rooij, Jeroen, Carlson, Chris, Peters, Ulrike, Berlivet, Soizik, Dostie, Josee, Claes Ohlsson, Uitterlinden, Andre, Goltzman, David, Pastinen, Tomi, Grundberg, Elin, Gauguier, Dominique, Orwoll, Eric, Karasik, David, Dahia, Chitra, Davey-Smith, George, Timpson, Nicholas, Soranzo, Nicole, Durbin, Richard, Wilson, Scott, Brown, Matthew, Spector, Tim, Cupples, L. Adrienne, Greenwood, Celia, Loomis, Cynthia, Ackert-Bicknell, Cheryl, Joyner, Alexandra, Jackson, Rebecca, Duncan, Emma, Evans, David, Rivadeneira, Fernando, Kiel, Douglas, Richards, Brent, McGill University = Université McGill [Montréal, Canada], Harvard Medical School [Boston] (HMS), Massachusetts General Hospital [Boston], Diamantina Institute, University of Queensland [Brisbane], University of Bristol [Bristol], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), School of public health, The University of Hong Kong (HKU), Memorial Sloan Kettering Cancer Center, The University of Texas M.D. Anderson Cancer Center [Houston], California Pacific Medical Center Research Institute, Oregon Health & Science University, Clinical Pharmacology, University of Gothenburg (GU), Genome Québec, The Wellcome Trust Sanger Institute [Cambridge], Hebrew SeniorLife [Boston], King‘s College London, Erasmus University Rotterdam, The Jackson Laboratory [Bar Harbor] (JAX), Umeå University, University of Wisconsin-Madison, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Washington [Seattle], Bar-Ilan University [Israël], Hospital for Special Surgery, University of Western Australia, University School of Medicine, University of Rochester Medical Center, Ohio State University [Columbus] (OSU), Royal Brisbane & Women's Hospital, and American Society for Bone and Mineral Research (ASBMR). USA.

Subjects
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience

Published
2014

45. TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization

Author

Wallmeier, Julia, primary, Shiratori, Hidetaka, additional, Dougherty, Gerard W., additional, Edelbusch, Christine, additional, Hjeij, Rim, additional, Loges, Niki T., additional, Menchen, Tabea, additional, Olbrich, Heike, additional, Pennekamp, Petra, additional, Raidt, Johanna, additional, Werner, Claudius, additional, Minegishi, Katsura, additional, Shinohara, Kyosuke, additional, Asai, Yasuko, additional, Takaoka, Katsuyoshi, additional, Lee, Chanjae, additional, Griese, Matthias, additional, Memari, Yasin, additional, Durbin, Richard, additional, Kolb-Kokocinski, Anja, additional, Sauer, Sascha, additional, Wallingford, John B., additional, Hamada, Hiroshi, additional, and Omran, Heymut, additional

Published
2016
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46. DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes

Author

Dougherty, Gerard W., primary, Loges, Niki T., additional, Klinkenbusch, Judith A., additional, Olbrich, Heike, additional, Pennekamp, Petra, additional, Menchen, Tabea, additional, Raidt, Johanna, additional, Wallmeier, Julia, additional, Werner, Claudius, additional, Westermann, Cordula, additional, Ruckert, Christian, additional, Mirra, Virginia, additional, Hjeij, Rim, additional, Memari, Yasin, additional, Durbin, Richard, additional, Kolb-Kokocinski, Anja, additional, Praveen, Kavita, additional, Kashef, Mohammad A., additional, Kashef, Sara, additional, Eghtedari, Fardin, additional, Häffner, Karsten, additional, Valmari, Pekka, additional, Baktai, György, additional, Aviram, Micha, additional, Bentur, Lea, additional, Amirav, Israel, additional, Davis, Erica E., additional, Katsanis, Nicholas, additional, Brueckner, Martina, additional, Shaposhnykov, Artem, additional, Pigino, Gaia, additional, Dworniczak, Bernd, additional, and Omran, Heymut, additional

Published
2016
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47. Deficient methylation and formylation of mt-tRNAMet wobble cytosine in a patient carrying mutations in NSUN3

Author

Van Haute, Lindsey, primary, Dietmann, Sabine, additional, Kremer, Laura, additional, Hussain, Shobbir, additional, Pearce, Sarah F., additional, Powell, Christopher A., additional, Rorbach, Joanna, additional, Lantaff, Rebecca, additional, Blanco, Sandra, additional, Sauer, Sascha, additional, Kotzaeridou, Urania, additional, Hoffmann, Georg F., additional, Memari, Yasin, additional, Kolb-Kokocinski, Anja, additional, Durbin, Richard, additional, Mayr, Johannes A., additional, Frye, Michaela, additional, Prokisch, Holger, additional, and Minczuk, Michal, additional

Published
2016
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48. 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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49. Whole-exome sequencing in an isolated population from the Dalmatian island of Vis

Author

Jeroncic, Ana, primary, Memari, Yasin, additional, Ritchie, Graham RS, additional, Hendricks, Audrey E, additional, Kolb-Kokocinski, Anja, additional, Matchan, Angela, additional, Vitart, Veronique, additional, Hayward, Caroline, additional, Kolcic, Ivana, additional, Glodzik, Dominik, additional, Wright, Alan F, additional, Rudan, Igor, additional, Campbell, Harry, additional, Durbin, Richard, additional, Polašek, Ozren, additional, Zeggini, Eleftheria, additional, and Boraska Perica, Vesna, additional

Published
2016
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50. New gene functions in megakaryopoiesis and platelet formation

Author

Gieger, Christian Radhakrishnan, Aparna Cvejic, Ana Tang, Weihong Porcu, Eleonora Pistis, Giorgio Serbanovic-Canic, Jovana Elling, Ulrich Goodall, Alison H. Labrune, Yann and Lopez, Lorna M. Maegi, Reedik Meacham, Stuart Okada, Yukinori Pirastu, Nicola Sorice, Rossella Teumer, Alexander and Voss, Katrin Zhang, Weihua Ramirez-Solis, Ramiro Bis, Joshua C. Ellinghaus, David Goegele, Martin Hottenga, Jouke-Jan Langenberg, Claudia Kovacs, Peter O'Reilly, Paul F. Shin, So-Youn Esko, Toenu Hartiala, Jaana Kanoni, Stavroula Murgia, Federico Parsa, Afshin Stephens, Jonathan and van der Harst, Pim van der Schoot, C. Ellen Allayee, Hooman and Attwood, Antony Balkau, Beverley Bastardot, Francois and Basu, Saonli Baumeister, Sebastian E. Biino, Ginevra Bomba, Lorenzo Bonnefond, Amelie Cambien, Francois Chambers, John C. Cucca, Francesco D'Adamo, Pio Davies, Gail de Boer, Rudolf A. de Geus, Eco J. C. Doering, Angela Elliott, Paul and Erdmann, Jeanette Evans, David M. Falchi, Mario Feng, Wei Folsom, Aaron R. Frazer, Ian H. Gibson, Quince D. and Glazer, Nicole L. Hammond, Chris Hartikainen, Anna-Liisa and Heckbert, Susan R. Hengstenberg, Christian Hersch, Micha and Illig, Thomas Loos, Ruth J. F. Jolley, Jennifer Khaw, Kay Tee Kuehnel, Brigitte Kyrtsonis, Marie-Christine Lagou, Vasiliki Lloyd-Jones, Heather Lumley, Thomas Mangino, Massimo Maschio, Andrea Leach, Irene Mateo McKnight, Barbara and Memari, Yasin Mitchell, Braxton D. Montgomery, Grant W. and Nakamura, Yusuke Nauck, Matthias Navis, Gerjan Noethlings, Ute Nolte, Ilja M. Porteous, David J. Pouta, Anneli and Pramstaller, Peter P. Pullat, Janne Ring, Susan M. Rotter, Jerome I. Ruggiero, Daniela Ruokonen, Aimo Sala, Cinzia and Samani, Nilesh J. Sambrook, Jennifer Schlessinger, David and Schreiber, Stefan Schunkert, Heribert Scott, James Smith, Nicholas L. Snieder, Harold Starr, John M. Stumvoll, Michael and Takahashi, Atsushi Tang, W. H. Wilson Taylor, Kent and Tenesa, Albert Thein, Swee Lay Toenjes, Anke Uda, Manuela and Ulivi, Sheila van Veldhuisen, Dirk J. Visscher, Peter M. and Voelker, Uwe Wichmann, H-Erich Wiggins, Kerri L. Willemsen, Gonneke Yang, Tsun-Po Zhao, Jing Hua Zitting, Paavo and Bradley, John R. Dedoussis, George V. Gasparini, Paolo and Hazen, Stanley L. Metspalu, Andres Pirastu, Mario Shuldiner, Alan R. van Pelt, L. Joost Zwaginga, Jaap-Jan Boomsma, Dorret I. Deary, Ian J. Franke, Andre Froguel, Philippe and Ganesh, Santhi K. Jarvelin, Marjo-Riitta Martin, Nicholas G. and Meisinger, Christa Psaty, Bruce M. Spector, Timothy D. and Wareham, Nicholas J. Akkerman, Jan-Willem N. Ciullo, Marina and Deloukas, Panos Greinacher, Andreas Jupe, Steve Kamatani, Naoyuki Khadake, Jyoti Kooner, Jaspal S. Penninger, Josef and Prokopenko, Inga Stemple, Derek Toniolo, Daniela and Wernisch, Lorenz Sanna, Serena Hicks, Andrew A. Rendon, Augusto Ferreira, Manuel A. Ouwehand, Willem H. Soranzo, Nicole

Abstract

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.

Published
2011

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