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193 results on '"Dobbins, Sara E."'

1. Genome-wide association analysis identifies a meningioma risk locus at 11p15.5

Author

Claus, Elizabeth B, Cornish, Alex J, Broderick, Peter, Schildkraut, Joellen M, Dobbins, Sara E, Holroyd, Amy, Calvocoressi, Lisa, Lu, Lingeng, Hansen, Helen M, Smirnov, Ivan, Walsh, Kyle M, Schramm, Johannes, Hoffmann, Per, Nöthen, Markus M, Jöckel, Karl-Heinz, Swerdlow, Anthony, Larsen, Signe Benzon, Johansen, Christoffer, Simon, Matthias, Bondy, Melissa, Wrensch, Margaret, Houlston, Richard S, and Wiemels, Joseph L

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Brain Cancer, Cancer, Genetics, Human Genome, Neurosciences, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Biomarkers, Tumor, Case-Control Studies, Chromosomes, Human, Pair 11, Female, Follow-Up Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Linkage Disequilibrium, Male, Meningeal Neoplasms, Meningioma, Middle Aged, Polymorphism, Single Nucleotide, Prognosis, Risk Factors, Young Adult, genome-wide association study, meningioma, polygenic, risk, single-nucleotide polymorphism, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundMeningiomas are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31.MethodsTo identify a susceptibility locus for meningioma, we conducted a meta-analysis of 2 GWAS, imputed using a merged reference panel from the 1000 Genomes Project and UK10K data, with validation in 2 independent sample series totaling 2138 cases and 12081 controls.ResultsWe identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges.ConclusionsThis finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.

Published
2018

5. Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer.

Author

Tomlinson, Ian PM, Carvajal-Carmona, Luis G, Dobbins, Sara E, Tenesa, Albert, Jones, Angela M, Howarth, Kimberley, Palles, Claire, Broderick, Peter, Jaeger, Emma EM, Farrington, Susan, Lewis, Annabelle, Prendergast, James GD, Pittman, Alan M, Theodoratou, Evropi, Olver, Bianca, Walker, Marion, Penegar, Steven, Barclay, Ella, Whiffin, Nicola, Martin, Lynn, Ballereau, Stephane, Lloyd, Amy, Gorman, Maggie, Lubbe, Steven, COGENT Consortium, CORGI Collaborators, EPICOLON Consortium, Howie, Bryan, Marchini, Jonathan, Ruiz-Ponte, Clara, Fernandez-Rozadilla, Ceres, Castells, Antoni, Carracedo, Angel, Castellvi-Bel, Sergi, Duggan, David, Conti, David, Cazier, Jean-Baptiste, Campbell, Harry, Sieber, Oliver, Lipton, Lara, Gibbs, Peter, Martin, Nicholas G, Montgomery, Grant W, Young, Joanne, Baird, Paul N, Gallinger, Steven, Newcomb, Polly, Hopper, John, Jenkins, Mark A, Aaltonen, Lauri A, Kerr, David J, Cheadle, Jeremy, Pharoah, Paul, Casey, Graham, Houlston, Richard S, and Dunlop, Malcolm G

Subjects
COGENT Consortium, CORGI Collaborators, EPICOLON Consortium, Humans, Colorectal Neoplasms, Genetic Predisposition to Disease, Intercellular Signaling Peptides and Proteins, Case-Control Studies, Signal Transduction, Gene Frequency, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Aged, Middle Aged, Male, Genetic Variation, Genome-Wide Association Study, Bone Morphogenetic Protein 2, Bone Morphogenetic Protein 4, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Genetics, Developmental Biology
Abstract

Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10)) and BMP2 (rs4813802, P = 4.65×10(-11)). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8)) and rs11632715 (P = 2.30×10(-10)). As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases.

Published
2011

6. Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33

Author

Houlston, Richard S, Cheadle, Jeremy, Dobbins, Sara E, Tenesa, Albert, Jones, Angela M, Howarth, Kimberley, Spain, Sarah L, Broderick, Peter, Domingo, Enric, Farrington, Susan, Prendergast, James GD, Pittman, Alan M, Theodoratou, Evi, Smith, Christopher G, Olver, Bianca, Walther, Axel, Barnetson, Rebecca A, Churchman, Michael, Jaeger, Emma EM, Penegar, Steven, Barclay, Ella, Martin, Lynn, Gorman, Maggie, Mager, Rachel, Johnstone, Elaine, Midgley, Rachel, Niittymäki, Iina, Tuupanen, Sari, Colley, James, Idziaszczyk, Shelley, Thomas, Huw JW, Lucassen, Anneke M, Evans, D Gareth R, Maher, Eamonn R, Maughan, Timothy, Dimas, Antigone, Dermitzakis, Emmanouil, Cazier, Jean-Baptiste, Aaltonen, Lauri A, Pharoah, Paul, Kerr, David J, Carvajal-Carmona, Luis G, Campbell, Harry, Dunlop, Malcolm G, and Tomlinson, Ian PM

Subjects
Prevention, Cancer, Genetics, Colo-Rectal Cancer, Human Genome, Digestive Diseases, Chromosome Mapping, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 3, Colorectal Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Meta-Analysis as Topic, Odds Ratio, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Risk Assessment, COGENT Consortium, CORGI Consortium, COIN Collaborative Group, COINB Collaborative Group, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10⁻¹⁰ and rs6687758, OR = 1.09, P = 2.27 × 10⁻⁹, 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10⁻⁸), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10⁻¹⁰ and rs7136702, OR = 1.06, P = 4.02 × 10⁻⁸) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10⁻¹⁰). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.

Published
2010

7. Investigation of clinical characteristics and genome associations in the 'UK Lipoedema' cohort

Author

Grigoriadis, Dionysios, Sackey, Ege, Riches, Katie, Van Zanten, Malou, Brice, Glen, England, Ruth, Mills, Mike, Dobbins, Sara E, Lee, Li Ling, Lipoedema Consortium, Genomics England Research Consortium, Jeffery, Steve, Dong, Liang, Savage, David B, Mortimer, Peter S, Keeley, Vaughan, Pittman, Alan, Gordon, Kristiana, Ostergaard, Pia, Mills, Mike [0000-0001-6316-4561], Dobbins, Sara E [0000-0001-5320-3467], Ostergaard, Pia [0000-0002-2190-1356], and Apollo - University of Cambridge Repository

Subjects
Medicine and health sciences, Genotype, Biology and life sciences, Lipedema, FOS: Physical sciences, Polymorphism, Single Nucleotide, United Kingdom, Research and analysis methods, Physical sciences, Quality of Life, Humans, Female, Genome-Wide Association Study, Research Article
Abstract

Funder: MRC Metabolic Disease Unit, Funder: National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Lipoedema is a chronic adipose tissue disorder mainly affecting women, causing excess subcutaneous fat deposition on the lower limbs with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is currently unclear. A tightly phenotyped cohort of 200 lipoedema patients was recruited from two UK specialist clinics. Objective clinical characteristics and measures of quality of life data were obtained. In an attempt to understand the genetic architecture of the disease better, genome-wide single nucleotide polymorphism (SNP) genotype data were obtained, and a genome wide association study (GWAS) was performed on 130 of the recruits. The analysis revealed genetic loci suggestively associated with the lipoedema phenotype, with further support provided by an independent cohort taken from the 100,000 Genomes Project. The top SNP rs1409440 (ORmeta ≈ 2.01, Pmeta ≈ 4 x 10-6) is located upstream of LHFPL6, which is thought to be involved with lipoma formation. Exactly how this relates to lipoedema is not yet understood. This first GWAS of a UK lipoedema cohort has identified genetic regions of suggestive association with the disease. Further replication of these findings in different populations is warranted.

Published
2022
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13. Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis

Author

Whiffin, Nicola, Hosking, Fay J., Farrington, Susan M., Palles, Claire, Dobbins, Sara E., Zgaga, Lina, Lloyd, Amy, Kinnersley, Ben, Gorman, Maggie, Tenesa, Albert, Broderick, Peter, Wang, Yufei, Barclay, Ella, Hayward, Caroline, Martin, Lynn, Buchanan, Daniel D., Win, Aung Ko, Hopper, John, Jenkins, Mark, Lindor, Noralane M., Newcomb, Polly A., Gallinger, Steve, Conti, David, Schumacher, Fred, Casey, Graham, Liu, Tao, Campbell, Harry, Lindblom, Annika, Houlston, Richard S., Tomlinson, Ian P., and Dunlop, Malcolm G.

Published
2014
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14. A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer

Author

Al-Tassan, Nada A., Whiffin, Nicola, Hosking, Fay J., Palles, Claire, Farrington, Susan M., Dobbins, Sara E., Harris, Rebecca, Gorman, Maggie, Tenesa, Albert, Meyer, Brian F., Wakil, Salma M., Kinnersley, Ben, Campbell, Harry, Martin, Lynn, Smith, Christopher G., Idziaszczyk, Shelley, Barclay, Ella, Maughan, Timothy S., Kaplan, Richard, Kerr, Rachel, Kerr, David, Buchanan, Daniel D., Win, Aung Ko, Hopper, John, Jenkins, Mark, Lindor, Noralane M., Newcomb, Polly A., Gallinger, Steve, Conti, David, Schumacher, Fred, Casey, Graham, Dunlop, Malcolm G., Tomlinson, Ian P., Cheadle, Jeremy P., and Houlston, Richard S.

Published
2015
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15. Deciphering the genetic architecture of low-penetrance susceptibility to colorectal cancer

Author

Whiffin, Nicola, Dobbins, Sara E., Hosking, Fay J., Palles, Claire, Tenesa, Albert, Wang, Yufei, Farrington, Susan M., Jones, Angela M., Broderick, Peter, Campbell, Harry, Newcomb, Polly A., Casey, Graham, Conti, David V., Schumacher, Fred, Gallinger, Steve, Lindor, Noralane M., Hopper, John, Jenkins, Mark, Dunlop, Malcolm G., Tomlinson, Ian P., and Houlston, Richard S.

Published
2013
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16. Chromosome 7p11.2 (EGFR) variation influences glioma risk

Author

Sanson, Marc, Hosking, Fay J., Shete, Sanjay, Zelenika, Diana, Dobbins, Sara E., Ma, Yussanne, Enciso-Mora, Victor, Idbaih, Ahmed, Delattre, Jean-Yves, Hoang-Xuan, Khe, Marie, Yannick, Boisselier, Blandine, Carpentier, Catherine, Wang, Xiao-Wei, Di Stefano, Anna Luisa, Labussière, Marianne, Gousias, Konstantinos, Schramm, Johannes, Boland, Anne, Lechner, Doris, Gut, Ivo, Armstrong, Georgina, Liu, Yanhong, Yu, Robert, Lau, Ching, Di Bernardo, Maria Chiara, Robertson, Lindsay B., Muir, Kenneth, Hepworth, Sarah, Swerdlow, Anthony, Schoemaker, Minouk J, Wichmann, H.-Erich, Müller, Martina, Schreiber, Stefan, Franke, Andre, Moebus, Susanne, Eisele, Lewin, Försti, Asta, Hemminki, Kari, Lathrop, Mark, Bondy, Melissa, Houlston, Richard S., and Simon, Matthias

Published
2011
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19. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author

Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., Hingorani, Aroon D., Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.

Abstract

Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

Published
2019
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20. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author

Planningssecretariaat HCK, Onderzoek Precision medicine, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Brain, Cancer, Cardiovasculaire Epidemiologie, Epi Methoden Team 6, Aios en Stafsecr. Cardiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 9, Team Medisch, Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, Van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, Van Der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'An, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., De Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, Van Der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M., Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-Van Der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothée, Roussel, Ronan, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Björn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., Hingorani, Aroon D., Planningssecretariaat HCK, Onderzoek Precision medicine, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Brain, Cancer, Cardiovasculaire Epidemiologie, Epi Methoden Team 6, Aios en Stafsecr. Cardiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 9, Team Medisch, Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, Van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, Van Der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'An, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., De Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, Van Der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M., Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-Van Der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothée, Roussel, Ronan, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Björn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.

Published
2019

21. Genome-wide association analysis identifies a meningioma risk locus at 11p15.5

Author

Simon, Matthias, Claus, Elisabeth B., Cornish, Alex J., Dobbins, Sara E., Schildkraut, Joellen M., Bondy, Melissa, Wrensch, Margaret, Houlston, Richard, and Wiemels, Joseph L.

Subjects
ddc: 610, otorhinolaryngologic diseases, macromolecular substances, 610 Medical sciences, Medicine, neoplasms, nervous system diseases
Abstract

Objective: The high incidence of meningiomas in neurofibromatosis type 2 patients provides strong evidence for an inherited predisposition to these tumors. An elevated risk of meningioma formation is also observed in several other genetic disorders. Several candidate gene polymorphisms have been investigated[for full text, please go to the a.m. URL], 69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie

Published
2018
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23. Search for rare protein altering variants influencing susceptibility to multiple myeloma

Author

Scales, Matthew, Chubb, Daniel, Dobbins, Sara E., Johnson, David C., Li, Ni, Sternberg, Michael J., Weinhold, Neils, Stein, Caleb, Jackson, Graham, Davies, Faith E., Walker, Brian A., Wardell, Christopher P., Houlston, Richard S., Morgan, Gareth J., and Wellcome Trust

Subjects
Male, EXPRESSION, Genotype, CARCINOMA, DNA Mutational Analysis, Gene Dosage, DNA-SEQUENCING DATA, Kinesins, Mitosis, Polymorphism, Single Nucleotide, Gene Frequency, Humans, Exome, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Genetic Association Studies, Aged, RISK, Science & Technology, inherited risk, PROLIFERATION, High-Throughput Nucleotide Sequencing, Cell Biology, FRAMEWORK, multiple myeloma, Oncology, Female, Transcriptome, Life Sciences & Biomedicine, exome sequencing, Research Paper
Abstract

The genetic basis underlying the inherited risk of developing multiple myeloma (MM) is largely unknown. To examine the impact of rare protein altering variants on the risk of developing MM we analyzed high-coverage exome sequencing data on 513 MM cases and 1,569 healthy controls, performing both single variant and gene burden tests. We did not identify any recurrent coding low-frequency alleles (1-5%) with moderate effect that were statistically associated with MM. In a gene burden analysis we did however identify a promising relationship between variation in the marrow kinetochore microtubule stromal gene KIF18A, which plays a role in control mitotic chromosome positioning dynamics, and risk of MM (P =3.6x10-6). Further analysis showed KIF18A displays a distinct pattern of expression across molecular subgroups of MM as well as being associated with patient survival. Our results inform future study design and provide a resource for contextualizing the impact of candidate MM susceptibility genes.

Published
2017

24. CanVar: A resource for sharing germline variation in cancer patients

Author

Chubb, Daniel, Broderick, Peter, Dobbins, Sara E., and Houlston, Richard S.

Subjects
Germline, Software Tool Article, NGS, CanVar, Genitourinary Cancers, cancer, colorectal cancer, Articles, Genomics, exome sequencing, ExAC, database
Abstract

The advent of high-throughput sequencing has accelerated our ability to discover genes predisposing to disease and is transforming clinical genomic sequencing. In both contexts knowledge of the spectrum and frequency of genetic variation in the general population and in disease cohorts is vital to the interpretation of sequencing data. While population level data is becoming increasingly available from publicly accessible sources, as exemplified by The Exome Aggregation Consortium (ExAC), the availability of large-scale disease-specific frequency information is limited. These data are of particular importance to contextualise findings from clinical mutation screens and small gene discovery projects. This is especially true for cancer, which is typified by a number of hereditary predisposition syndromes. Although mutation frequencies in tumours are available from resources such as Cosmic and The Cancer Genome Atlas, a similar facility for germline variation is lacking. Here we present the Cancer Variation Resource (CanVar) an online database which has been developed using the ExAC framework to provide open access to germline variant frequency data from the sequenced exomes of cancer patients. In its first release, CanVar catalogues the exomes of 1,006 familial early-onset colorectal cancer (CRC) patients sequenced at The Institute of Cancer Research. It is anticipated that CanVar will host data for additional cancers, providing a resource for others studying cancer predisposition and an example of how the research community can utilise the ExAC framework to share sequencing data.

Published
2016

25. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author

Schmidt, Amand F, primary, Holmes, Michael V, additional, Preiss, David, additional, Swerdlow, Daniel, additional, Denaxas, Spiros, additional, Fatemifar, Ghazaleh, additional, Faraway, Rupert, additional, Finan, Chris, additional, Lumbers, Tom, additional, Henry, Albert, additional, Valentine, Dennis, additional, Fairhurst-Hunter, Zammy, additional, Hartwig, Fernando Pires, additional, Horta, Bernardo Lessa, additional, Hypponen, Elina, additional, Power, Christine, additional, Moldovan, Max, additional, van Iperen, Erik, additional, Hovingh, Kees, additional, Demuth, Ilja, additional, Norman, Kristina, additional, Steinhagen-Thiessen, Elisabeth, additional, Demuth, Juri, additional, Bertram, Lars, additional, Lill, Christina M, additional, Coassin, Stefan, additional, Willeit, Johann, additional, Kiechl, Stefan, additional, Willeit, Karin, additional, Mason, Dan, additional, Wright, John, additional, Morris, Richard, additional, Wanamethee, Goya, additional, Whincup, Peter, additional, Ben-Shlomo, Yoav, additional, McLachlan, Stela, additional, Price, Jackie F., additional, Kivimaki, Mika, additional, Welch, Catherine, additional, Sanchez-Galvez, Adelaida, additional, Marques-Vidal, Pedro, additional, Nicolaides, Andrew, additional, Panayiotou, Andrie G., additional, Onland-Moret, N. Charlotte, additional, van der Schouw, Yvonne T., additional, Matullo, Giuseppe, additional, Fiorito, Giovanni, additional, Guarrera, Simonetta, additional, Sacerdote, Carlotta, additional, Wareham, Nicholas J, additional, Langenberg, Claudia, additional, Scott, Robert A, additional, Luan, Jian’an, additional, Bobak, Martin, additional, Malyutina, Sofia, additional, Pajak, Andrzej, additional, Kubinova, Ruzena, additional, Tamosiunas, Abdonas, additional, Pikhart, Hynek, additional, Grarup, Niels, additional, Pedersen, Oluf, additional, Hansen, Torben, additional, Linneberg, Allan, additional, Jess, Tine, additional, Cooper, Jackie, additional, Humphries, Steve E, additional, Brilliant, Murray, additional, Kitchner, Terrie, additional, Hakonarson, Hakon, additional, Carrell, David S., additional, McCarty, Catherine A., additional, Lester, Kirchner H, additional, Larson, Eric B., additional, Crosslin, David R., additional, Andrade, Mariza de, additional, Roden, Dan M, additional, Denny, Joshua C, additional, Carty, Cara, additional, Hancock, Stephen, additional, Attia, John, additional, Holliday, Elizabeth, additional, Scott, Rodney, additional, Schofield, Peter, additional, O’Donnell, Martin, additional, Yusuf, Salim, additional, Chong, Michael, additional, Pare, Guillaume, additional, van der Harst, Pim, additional, Said, M. Abdullah, additional, Eppinga, Ruben N., additional, Verweij, Niek, additional, Snieder, Harold, additional, Christen, Tim, additional, Mook-Kanamori, D.O., additional, Gustafsson, Stefan, additional, Lind, Lars, additional, Ingelsson, Erik, additional, Pazoki, Raha, additional, Franco, Oscar, additional, Hofman, Albert, additional, Uitterlinden, Andre, additional, Dehghan, Abbas, additional, Teumer, Alexander, additional, Baumeister, Sebastian, additional, Dörr, Marcus, additional, Lerch, Markus M., additional, Völker, Uwe, additional, Völzke, Henry, additional, Ward, Joey, additional, Pell, Jill P, additional, Meade, Tom, additional, Christophersen, Ingrid E., additional, Maitland-van der Zee, Anke H., additional, Baranova, Ekaterina V., additional, Young, Robin, additional, Ford, Ian, additional, Campbell, Archie, additional, Padmanabhan, Sandosh, additional, Bots, Michiel L, additional, Grobbee, Diederick E., additional, Froguel, Philippe, additional, Thuillier, Dorothée, additional, Roussel, Ronan, additional, Bonnefond, Amelie, additional, Cariou, Bertrand, additional, Smart, Melissa, additional, Bao, Yanchun, additional, Kumari, Meena, additional, Mahajan, Anubha, additional, Hopewell, Jemma C., additional, Seshadri, Sudha, additional, Dale, Caroline, additional, Costa, Rui Providencia E, additional, Ridker, Paul M, additional, Chasman, Daniel I., additional, Reiner, Alex P., additional, Ritchie, Marylyn D, additional, Lange, Leslie A, additional, Cornish, Alex J., additional, Dobbins, Sara E., additional, Hemminki, Kari, additional, Kinnersley, Ben, additional, Sanson, Marc, additional, Labreche, Karim, additional, Simon, Matthias, additional, Bondy, Melissa, additional, Law, Philip, additional, Speedy, Helen, additional, Allan, James, additional, Li, Ni, additional, Went, Molly, additional, Weinhold, Niels, additional, Morgan, Gareth, additional, Sonneveld, Pieter, additional, Nilsson, Björn, additional, Goldschmidt, Hartmut, additional, Sud, Amit, additional, Engert, Andreas, additional, Hansson, Markus, additional, Hemingway, Harry, additional, Asselbergs, Folkert W, additional, Patel, Riyaz S, additional, Keating, Brendan J, additional, Sattar, Naveed, additional, Houlston, Richard, additional, Casas, Juan P, additional, and Hingorani, Aroon D, additional

Published
2018
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26. SEMA4A variation and risk of colorectal cancer

Author

Kinnersley, Ben, Chubb, Daniel, Dobbins, Sara E, Frampton, Matthew, Buch, Stephan, Timofeeva, Maria, Castellvi-Bel, Sergi, Farrington, Susan, Forsti, Asta, Hampe, Jochen, Hemminki, Kari, Hofstra, Robert M W, Northwood, Emma, Palles, Claire, Pinheiro, Manuela, Ruiz-Ponte, Clara, Schafmayer, Clemens, Teixeira, Manuel R, Westers, Helga, Van Wezel, Tom, Bishop, D Tim, Tomlinson, Ian, Dunlop, Malcolm, and Houlston, Richard S

Published
2016

27. Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2 Enhancer Polymorphism

Author

Li, Ni, primary, Johnson, David C., additional, Weinhold, Niels, additional, Kimber, Scott, additional, Dobbins, Sara E., additional, Mitchell, Jonathan S., additional, Kinnersley, Ben, additional, Sud, Amit, additional, Law, Philip J., additional, Orlando, Giulia, additional, Scales, Matthew, additional, Wardell, Christopher P., additional, Försti, Asta, additional, Hoang, Phuc H., additional, Went, Molly, additional, Holroyd, Amy, additional, Hariri, Fadi, additional, Pastinen, Tomi, additional, Meissner, Tobias, additional, Goldschmidt, Hartmut, additional, Hemminki, Kari, additional, Morgan, Gareth J., additional, Kaiser, Martin, additional, and Houlston, Richard S., additional

Published
2017
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28. Search for rare protein altering variants influencing susceptibility to multiple myeloma

Author

Scales, Matthew, primary, Chubb, Daniel, additional, Dobbins, Sara E., additional, Johnson, David C., additional, Li, Ni, additional, Sternberg, Michael J., additional, Weinhold, Neils, additional, Stein, Caleb, additional, Jackson, Graham, additional, Davies, Faith E., additional, Walker, Brian A., additional, Wardell, Christopher P., additional, Houlston, Richard S., additional, and Morgan, Gareth J., additional

Published
2017
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30. TCF12 is mutated in anaplastic oligodendroglioma

Author

Labreche, Karim, Simeonova, Iva, Kamoun, Aurélie, Gleize, Vincent, Chubb, Daniel, Letouzé, Eric, Riazalhosseini, Yasser, Dobbins, Sara E., Elarouci, Nabila, Ducray, Francois, De Reyniès, Aurélien, Zelenika, Diana, Wardell, Christopher P., Frampton, Mathew, Saulnier, Olivier, Pastinen, Tomi, Hallout, Sabrina, Figarella-Branger, Dominique, Dehais, Caroline, Idbaih, Ahmed, Mokhtari, Karima, Delattre, Jean-Yves, Huillard, Emmanuelle, Lathrop, G Mark, Sanson, Marc, Houlston, Richard S., Institute of Cancer Research, Belmont, Sutton, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, McGill University = Université McGill [Montréal, Canada], Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital de la Timone [CHU - APHM] (TIMONE), Université de la Méditerranée - Aix-Marseille 2, UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Neuropathologie Raymond Escourolle, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ligue Nationale Contre le Cancer (LNCC), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], and HAL UPMC, Gestionnaire

Subjects
Transcriptional Activation, [SDV.GEN]Life Sciences [q-bio]/Genetics, Brain Neoplasms, Mutation, Oligodendroglioma, Basic Helix-Loop-Helix Transcription Factors, Down-Regulation, Humans, [SDV.GEN] Life Sciences [q-bio]/Genetics, Article
Abstract

Anaplastic oligodendroglioma (AO) are rare primary brain tumours that are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosomes 1p/19q co-deletion and an IDH mutation. Here we analysed 51 AO by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall, 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. Eighty percent of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frameshift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumour type. Our analysis provides further insights into the unique and shared pathways driving AO., Anaplastic oligodendrogliomas are rare and incurable primary brain tumours with few treatment options. Here Labreche et al. perform whole-exome sequencing and identify recurring mutations in transcription factor TCF12, which are associated with aggressive tumours.

Published
2015

31. Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer

Author

Chubb, Daniel, primary, Broderick, Peter, additional, Dobbins, Sara E., additional, Frampton, Matthew, additional, Kinnersley, Ben, additional, Penegar, Steven, additional, Price, Amy, additional, Ma, Yussanne P., additional, Sherborne, Amy L., additional, Palles, Claire, additional, Timofeeva, Maria N., additional, Bishop, D. Timothy, additional, Dunlop, Malcolm G., additional, Tomlinson, Ian, additional, and Houlston, Richard S., additional

Published
2016
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32. Correspondence: SEMA4A variation and risk of colorectal cancer

Author

Kinnersley, Ben, primary, Chubb, Daniel, additional, Dobbins, Sara E., additional, Frampton, Matthew, additional, Buch, Stephan, additional, Timofeeva, Maria N., additional, Castellví-Bel, Sergi, additional, Farrington, Susan M., additional, Forsti, Asta, additional, Hampe, Jochen, additional, Hemminki, Kari, additional, Hofstra, Robert M. W., additional, Northwood, Emma, additional, Palles, Claire, additional, Pinheiro, Manuela, additional, Ruiz-Ponte, Clara, additional, Schafmayer, Clemens, additional, Teixeira, Manuel R., additional, Westers, Helga, additional, van Wezel, Tom, additional, Timothy Bishop, D., additional, Tomlinson, Ian, additional, Dunlop, Malcolm G., additional, and Houlston, Richard S., additional

Published
2016
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33. Erratum: A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer

Author

Al-Tassan, Nada A., primary, Whiffin, Nicola, additional, Hosking, Fay J., additional, Palles, Claire, additional, Farrington, Susan M., additional, Dobbins, Sara E., additional, Harris, Rebecca, additional, Gorman, Maggie, additional, Tenesa, Albert, additional, Meyer, Brian F., additional, Wakil, Salma M., additional, Kinnersley, Ben, additional, Campbell, Harry, additional, Martin, Lynn, additional, Smith, Christopher G., additional, Idziaszczyk, Shelley, additional, Barclay, Ella, additional, Maughan, Timothy S., additional, Kaplan, Richard, additional, Kerr, Rachel, additional, Kerr, David, additional, Buchanan, Daniel D., additional, Win, Aung Ko, additional, Hopper, John, additional, Jenkins, Mark, additional, Lindor, Noralane M., additional, Newcomb, Polly A., additional, Gallinger, Steve, additional, Conti, David, additional, Schumacher, Fred, additional, Casey, Graham, additional, Dunlop, Malcolm G., additional, Tomlinson, Ian P., additional, Cheadle, Jeremy P., additional, and Houlston, Richard S., additional

Published
2015
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35. Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

Author

Dunlop, Malcolm G, Dobbins, Sara E, Farrington, Susan M, Jones, Angela M, Palles, Claire, Whiffin, Nicola, Tenesa, Albert, Spain, Sarah, Broderick, Peter, Ooi, Li-Yin, Domingo, Enric, Smillie, Claire, Henrion, Marc, Frampton, Matthew, Martin, Lynn, Grimes, Graeme, Gorman, Maggie, Semple, Colin, Ma, Yusanne P, Barclay, Ella, Prendergast, James, Cazier, Jean-Baptiste, Olver, Bianca, Penegar, Steven, Lubbe, Steven, Chandler, Ian, Carvajal-Carmona, Luis G, Ballereau, Stephane, Lloyd, Amy, Vijayakrishnan, Jayaram, Zgaga, Lina, Rudan, Igor, Theodoratou, Evropi, Colorectal Tumour Gene Identification (CORGI) Consortium, Starr, John M, Deary, Ian, Kirac, Iva, Kovacevic, Dujo, Aaltonen, Lauri A, Renkonen-Sinisalo, Laura, Mecklin, Jukka-Pekka, Matsuda, Koichi, Nakamura, Yusuke, Okada, Yukinori, Gallinger, Steven, Duggan, David J, Conti, David, Newcomb, Polly A, Hopper, John L, Jenkins, Mark A, Schumacher, Fredrick, Casey, Graham, Easton, Douglas, Shah, Mitul, Pharoah, Paul, Lindblom, Annika, Liu, Tao, Swedish Low-Risk Colorectal Cancer Study Group, Smith, Christopher G, West, Hannah, Cheadle, Jeremy P, COIN Collaborative Group, Midgley, Rachel, Kerr, David J, Campbell, Harry, Tomlinson, Ian, Houlston, Richard S, Dunlop, Malcolm G, Dobbins, Sara E, Farrington, Susan M, Jones, Angela M, Palles, Claire, Whiffin, Nicola, Tenesa, Albert, Spain, Sarah, Broderick, Peter, Ooi, Li-Yin, Domingo, Enric, Smillie, Claire, Henrion, Marc, Frampton, Matthew, Martin, Lynn, Grimes, Graeme, Gorman, Maggie, Semple, Colin, Ma, Yusanne P, Barclay, Ella, Prendergast, James, Cazier, Jean-Baptiste, Olver, Bianca, Penegar, Steven, Lubbe, Steven, Chandler, Ian, Carvajal-Carmona, Luis G, Ballereau, Stephane, Lloyd, Amy, Vijayakrishnan, Jayaram, Zgaga, Lina, Rudan, Igor, Theodoratou, Evropi, Colorectal Tumour Gene Identification (CORGI) Consortium, Starr, John M, Deary, Ian, Kirac, Iva, Kovacevic, Dujo, Aaltonen, Lauri A, Renkonen-Sinisalo, Laura, Mecklin, Jukka-Pekka, Matsuda, Koichi, Nakamura, Yusuke, Okada, Yukinori, Gallinger, Steven, Duggan, David J, Conti, David, Newcomb, Polly A, Hopper, John L, Jenkins, Mark A, Schumacher, Fredrick, Casey, Graham, Easton, Douglas, Shah, Mitul, Pharoah, Paul, Lindblom, Annika, Liu, Tao, Swedish Low-Risk Colorectal Cancer Study Group, Smith, Christopher G, West, Hannah, Cheadle, Jeremy P, COIN Collaborative Group, Midgley, Rachel, Kerr, David J, Campbell, Harry, Tomlinson, Ian, and Houlston, Richard S

Abstract

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

Published
2013

36. Developmental timing of mutations revealed by whole-genome sequencing of twins with acute lymphoblastic leukemia

Author

Ma, Y, Dobbins, S, Sherborne, A, Chubb, D, Galbiati, M, Cazzaniga, G, Micalizzi, C, Tearle, R, Lloyd, A, Hain, R, Greaves, M, Houlston, R, Ma, Yussanne, Dobbins, Sara E, Sherborne, Amy L, Chubb, Daniel, Galbiati, Marta, Cazzaniga, Giovanni, Micalizzi, Concetta, Tearle, Rick, Lloyd, Amy L, Hain, Richard, Greaves, Mel, Houlston, Richard S, Ma, Y, Dobbins, S, Sherborne, A, Chubb, D, Galbiati, M, Cazzaniga, G, Micalizzi, C, Tearle, R, Lloyd, A, Hain, R, Greaves, M, Houlston, R, Ma, Yussanne, Dobbins, Sara E, Sherborne, Amy L, Chubb, Daniel, Galbiati, Marta, Cazzaniga, Giovanni, Micalizzi, Concetta, Tearle, Rick, Lloyd, Amy L, Hain, Richard, Greaves, Mel, and Houlston, Richard S

Abstract

Acute lymphoblastic leukemia (ALL) is the major pediatric cancer. At diagnosis, the developmental timing of mutations contributing critically to clonal diversification and selection can be buried in the leukemia's covert natural history. Concordance of ALL in monozygotic, monochorionic twins is a consequence of intraplacental spread of an initiated preleukemic clone. Studying monozygotic twins with ALL provides a unique means of uncovering the timeline of mutations contributing to clonal evolution, pre- and postnatally. We sequenced the whole genomes of leukemic cells from two twin pairs with ALL to comprehensively characterize acquired somatic mutations in ALL, elucidating the developmental timing of all genetic lesions. Shared, prenatal, coding-region single-nucleotide variants were limited to the putative initiating lesions. All other nonsynonymous single-nucleotide variants were distinct between tumors and, therefore, secondary and postnatal. These changes occurred in a background of noncoding mutational changes that were almost entirely discordant in twin pairs and likely passenger mutations acquired during leukemic cell proliferation.

Published
2013

37. Common variation at 10p12.31 near MLLT10 influences meningioma risk

Author

Dobbins, Sara E., Broderick, Peter, Melin, Beatrice, Feychting, Maria, Johansen, Christoffer, Andersson, Ulrika, Brännström, Thomas, Schramm, Johannes, Olver, Bianca, Lloyd, Amy, Ma, Yussanne P., Hosking, Fay J., Lönn, Stefan, Ahlbom, Anders, Henriksson, Roger, Schoemaker, Minouk J., Hepworth, Sarah J., Hoffmann, Per, Muehleisen, Thomas W., Noethen, Markus M., Moebus, Susanne, Eisele, Lewin, Kosteljanetz, Michael, Muir, Kenneth, Swerdlow, Anthony, Simon, Matthias, Houlston, Richard S., Dobbins, Sara E., Broderick, Peter, Melin, Beatrice, Feychting, Maria, Johansen, Christoffer, Andersson, Ulrika, Brännström, Thomas, Schramm, Johannes, Olver, Bianca, Lloyd, Amy, Ma, Yussanne P., Hosking, Fay J., Lönn, Stefan, Ahlbom, Anders, Henriksson, Roger, Schoemaker, Minouk J., Hepworth, Sarah J., Hoffmann, Per, Muehleisen, Thomas W., Noethen, Markus M., Moebus, Susanne, Eisele, Lewin, Kosteljanetz, Michael, Muir, Kenneth, Swerdlow, Anthony, Simon, Matthias, and Houlston, Richard S.

Abstract

To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.

Published
2011
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38. Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk

Author

Crowther-Swanepoel, Dalemari, Broderick, Peter, Di Bernardo, Maria Chiara, Dobbins, Sara E., Torres, Maria, Mansouri, Mahmoud, Ruiz-Ponte, Clara, Enjuanes, Anna, Rosenquist, Richard, Carracedo, Angel, Jurlander, Jesper, Campo, Elias, Juliusson, Gunnar, Montserrat, Emilio, Smedby, Karin E., Dyer, Martin J. S., Matutes, Estella, Dearden, Claire, Sunter, Nicola J., Hall, Andrew G., Mainou-Fowler, Tryfonia, Jackson, Graham H., Summerfield, Geoffrey, Harris, Robert J., Pettitt, Andrew R., Allsup, David J., Bailey, James R., Pratt, Guy, Pepper, Chris, Fegan, Chris, Parker, Anton, Oscier, David, Allan, James M., Catovsky, Daniel, Houlston, Richard S., Crowther-Swanepoel, Dalemari, Broderick, Peter, Di Bernardo, Maria Chiara, Dobbins, Sara E., Torres, Maria, Mansouri, Mahmoud, Ruiz-Ponte, Clara, Enjuanes, Anna, Rosenquist, Richard, Carracedo, Angel, Jurlander, Jesper, Campo, Elias, Juliusson, Gunnar, Montserrat, Emilio, Smedby, Karin E., Dyer, Martin J. S., Matutes, Estella, Dearden, Claire, Sunter, Nicola J., Hall, Andrew G., Mainou-Fowler, Tryfonia, Jackson, Graham H., Summerfield, Geoffrey, Harris, Robert J., Pettitt, Andrew R., Allsup, David J., Bailey, James R., Pratt, Guy, Pepper, Chris, Fegan, Chris, Parker, Anton, Oscier, David, Allan, James M., Catovsky, Daniel, and Houlston, Richard S.

Abstract

To identify new risk variants for chronic lymphocytic leukemia (CLL), we conducted a genome-wide association study of 299,983 tagging SNPs, with validation in four additional series totaling 2,503 cases and 5,789 controls. We identified four new risk loci for CLL at 2q37.3 (rs757978, FARP2; odds ratio (OR) = 1.39; P = 2.11 x 10(-9)), 8q24.21 (rs2456449; OR = 1.26; P = 7.84 x 10(-10)), 15q21.3 (rs7169431; OR = 1.36; P = 4.74 x 10(-7)) and 16q24.1 (rs305061; OR = 1.22; P = 3.60 x 10(-7)). We also found evidence for risk loci at 15q25.2 (rs783540, CPEB1; OR = 1.18; P = 3.67 x 10(-6)) and 18q21.1 (rs1036935; OR = 1.22; P = 2.28 x 10(-6)). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy.

Published
2010
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39. A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)

Author

Enciso-Mora, Victor, Broderick, Peter, Ma, Yussanne, Jarrett, Ruth F., Hjalgrim, Henrik, Hemminki, Kari, van den Berg, Anke, Olver, Bianca, Lloyd, Amy, Dobbins, Sara E., Lightfoot, Tracy, van Leeuwen, Flora E., Foersti, Asta, Diepstra, Arjan, Broeks, Annegien, Vijayakrishnan, Jayaram, Shield, Lesley, Lake, Annette, Montgomery, Dorothy, Roman, Eve, Engert, Andreas, von Strandmann, Elke Pogge, Reiners, Katrin S., Nolte, Ilja M., Smedby, Karin E., Adami, Hans-Olov, Russell, Nicola S., Glimelius, Bengt, Hamilton-Dutoit, Stephen, de Bruin, Marieke, Ryder, Lars P., Molin, Daniel, Sorensen, Karina Meden, Chang, Ellen T., Taylor, Malcolm, Cooke, Rosie, Hofstra, Robert, Westers, Helga, van Wezel, Tom, van Eijk, Ronald, Ashworth, Alan, Rostgaard, Klaus, Melbye, Mads, Swerdlow, Anthony J., Houlston, Richard S., Enciso-Mora, Victor, Broderick, Peter, Ma, Yussanne, Jarrett, Ruth F., Hjalgrim, Henrik, Hemminki, Kari, van den Berg, Anke, Olver, Bianca, Lloyd, Amy, Dobbins, Sara E., Lightfoot, Tracy, van Leeuwen, Flora E., Foersti, Asta, Diepstra, Arjan, Broeks, Annegien, Vijayakrishnan, Jayaram, Shield, Lesley, Lake, Annette, Montgomery, Dorothy, Roman, Eve, Engert, Andreas, von Strandmann, Elke Pogge, Reiners, Katrin S., Nolte, Ilja M., Smedby, Karin E., Adami, Hans-Olov, Russell, Nicola S., Glimelius, Bengt, Hamilton-Dutoit, Stephen, de Bruin, Marieke, Ryder, Lars P., Molin, Daniel, Sorensen, Karina Meden, Chang, Ellen T., Taylor, Malcolm, Cooke, Rosie, Hofstra, Robert, Westers, Helga, van Wezel, Tom, van Eijk, Ronald, Ashworth, Alan, Rostgaard, Klaus, Melbye, Mads, Swerdlow, Anthony J., and Houlston, Richard S.

Abstract

To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10−8), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10−13) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10−8). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10−50). These data provide new insight into the pathogenesis of cHL.

Published
2010
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40. Genome-wide association study identifies five susceptibility loci for glioma.

Author

Shete, Sanjay, Hosking, Fay J, Robertson, Lindsay B, Dobbins, Sara E, Sanson, Marc, Malmer, Beatrice, Simon, Matthias, Marie, Yannick, Boisselier, Blandine, Delattre, Jean-Yves, Hoang-Xuan, Khe, El Hallani, Soufiane, Idbaih, Ahmed, Zelenika, Diana, Andersson, Ulrika, Henriksson, Roger, Bergenheim, A Tommy, Feychting, Maria, Lönn, Stefan, Ahlbom, Anders, Schramm, Johannes, Linnebank, Michael, Hemminki, Kari, Kumar, Rajiv, Hepworth, Sarah J, Price, Amy, Armstrong, Georgina, Liu, Yanhong, Gu, Xiangjun, Yu, Robert, Lau, Ching, Schoemaker, Minouk, Muir, Kenneth, Swerdlow, Anthony, Lathrop, Mark, Bondy, Melissa, Houlston, Richard S, Shete, Sanjay, Hosking, Fay J, Robertson, Lindsay B, Dobbins, Sara E, Sanson, Marc, Malmer, Beatrice, Simon, Matthias, Marie, Yannick, Boisselier, Blandine, Delattre, Jean-Yves, Hoang-Xuan, Khe, El Hallani, Soufiane, Idbaih, Ahmed, Zelenika, Diana, Andersson, Ulrika, Henriksson, Roger, Bergenheim, A Tommy, Feychting, Maria, Lönn, Stefan, Ahlbom, Anders, Schramm, Johannes, Linnebank, Michael, Hemminki, Kari, Kumar, Rajiv, Hepworth, Sarah J, Price, Amy, Armstrong, Georgina, Liu, Yanhong, Gu, Xiangjun, Yu, Robert, Lau, Ching, Schoemaker, Minouk, Muir, Kenneth, Swerdlow, Anthony, Lathrop, Mark, Bondy, Melissa, and Houlston, Richard S

Abstract

To identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma at 5p15.33 (rs2736100, TERT; P = 1.50 x 10(-17)), 8q24.21 (rs4295627, CCDC26; P = 2.34 x 10(-18)), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 x 10(-15)), 20q13.33 (rs6010620, RTEL1; P = 2.52 x 10(-12)) and 11q23.3 (rs498872, PHLDB1; P = 1.07 x 10(-8)). These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.

Published
2009
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41. Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk

Author

Chubb, Daniel, primary, Weinhold, Niels, additional, Broderick, Peter, additional, Chen, Bowang, additional, Johnson, David C, additional, Försti, Asta, additional, Vijayakrishnan, Jayaram, additional, Migliorini, Gabriele, additional, Dobbins, Sara E, additional, Holroyd, Amy, additional, Hose, Dirk, additional, Walker, Brian A, additional, Davies, Faith E, additional, Gregory, Walter A, additional, Jackson, Graham H, additional, Irving, Julie A, additional, Pratt, Guy, additional, Fegan, Chris, additional, Fenton, James A L, additional, Neben, Kai, additional, Hoffmann, Per, additional, Nöthen, Markus M, additional, Mühleisen, Thomas W, additional, Eisele, Lewin, additional, Ross, Fiona M, additional, Straka, Christian, additional, Einsele, Hermann, additional, Langer, Christian, additional, Dörner, Elisabeth, additional, Allan, James M, additional, Jauch, Anna, additional, Morgan, Gareth J, additional, Hemminki, Kari, additional, Houlston, Richard S, additional, and Goldschmidt, Hartmut, additional

Published
2013
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43. The CCND1 c.870G>A polymorphism is a risk factor for t(11;14)(q13;q32) multiple myeloma

Author

Weinhold, Niels, primary, Johnson, David C, additional, Chubb, Daniel, additional, Chen, Bowang, additional, Försti, Asta, additional, Hosking, Fay J, additional, Broderick, Peter, additional, Ma, Yussanne P, additional, Dobbins, Sara E, additional, Hose, Dirk, additional, Walker, Brian A, additional, Davies, Faith E, additional, Kaiser, Martin F, additional, Li, Ni L, additional, Gregory, Walter A, additional, Jackson, Graham H, additional, Witzens-Harig, Mathias, additional, Neben, Kai, additional, Hoffmann, Per, additional, Nöthen, Markus M, additional, Mühleisen, Thomas W, additional, Eisele, Lewin, additional, Ross, Fiona M, additional, Jauch, Anna, additional, Goldschmidt, Hartmut, additional, Houlston, Richard S, additional, Morgan, Gareth J, additional, and Hemminki, Kari, additional

Published
2013
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44. Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2Enhancer Polymorphism

Author

Li, Ni, Johnson, David C., Weinhold, Niels, Kimber, Scott, Dobbins, Sara E., Mitchell, Jonathan S., Kinnersley, Ben, Sud, Amit, Law, Philip J., Orlando, Giulia, Scales, Matthew, Wardell, Christopher P., Försti, Asta, Hoang, Phuc H., Went, Molly, Holroyd, Amy, Hariri, Fadi, Pastinen, Tomi, Meissner, Tobias, Goldschmidt, Hartmut, Hemminki, Kari, Morgan, Gareth J., Kaiser, Martin, and Houlston, Richard S.

Abstract

Multiple myeloma (MM) is a malignancy of plasma cells. Genome-wide association studies have shown that variation at 5q15 influences MM risk. Here, we have sought to decipher the causal variant at 5q15 and the mechanism by which it influences tumorigenesis. We show that rs6877329 G > C resides in a predicted enhancer element that physically interacts with the transcription start site of ELL2. The rs6877329-C risk allele is associated with reduced enhancer activity and lowered ELL2expression. Since ELL2is critical to the B cell differentiation process, reduced ELL2expression is consistent with inherited genetic variation contributing to arrest of plasma cell development, facilitating MM clonal expansion. These data provide evidence for a biological mechanism underlying a hereditary risk of MM at 5q15.

Published
2017
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45. Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk

Author

Broderick, Peter, primary, Chubb, Daniel, additional, Johnson, David C, additional, Weinhold, Niels, additional, Försti, Asta, additional, Lloyd, Amy, additional, Olver, Bianca, additional, Ma, Yussanne P, additional, Dobbins, Sara E, additional, Walker, Brian A, additional, Davies, Faith E, additional, Gregory, Walter A, additional, Child, J Anthony, additional, Ross, Fiona M, additional, Jackson, Graham H, additional, Neben, Kai, additional, Jauch, Anna, additional, Hoffmann, Per, additional, Mühleisen, Thomas W, additional, Nöthen, Markus M, additional, Moebus, Susanne, additional, Tomlinson, Ian P, additional, Goldschmidt, Hartmut, additional, Hemminki, Kari, additional, Morgan, Gareth J, additional, and Houlston, Richard S, additional

Published
2011
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46. Common variation at 10p12.31 near MLLT10 influences meningioma risk

Author

Dobbins, Sara E, primary, Broderick, Peter, additional, Melin, Beatrice, additional, Feychting, Maria, additional, Johansen, Christoffer, additional, Andersson, Ulrika, additional, Brännström, Thomas, additional, Schramm, Johannes, additional, Olver, Bianca, additional, Lloyd, Amy, additional, Ma, Yussanne P, additional, Hosking, Fay J, additional, Lönn, Stefan, additional, Ahlbom, Anders, additional, Henriksson, Roger, additional, Schoemaker, Minouk J, additional, Hepworth, Sarah J, additional, Hoffmann, Per, additional, Mühleisen, Thomas W, additional, Nöthen, Markus M, additional, Moebus, Susanne, additional, Eisele, Lewin, additional, Kosteljanetz, Michael, additional, Muir, Kenneth, additional, Swerdlow, Anthony, additional, Simon, Matthias, additional, and Houlston, Richard S, additional

Published
2011
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47. A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)

Author

Enciso-Mora, Victor, primary, Broderick, Peter, additional, Ma, Yussanne, additional, Jarrett, Ruth F, additional, Hjalgrim, Henrik, additional, Hemminki, Kari, additional, van den Berg, Anke, additional, Olver, Bianca, additional, Lloyd, Amy, additional, Dobbins, Sara E, additional, Lightfoot, Tracy, additional, van Leeuwen, Flora E, additional, Försti, Asta, additional, Diepstra, Arjan, additional, Broeks, Annegien, additional, Vijayakrishnan, Jayaram, additional, Shield, Lesley, additional, Lake, Annette, additional, Montgomery, Dorothy, additional, Roman, Eve, additional, Engert, Andreas, additional, von Strandmann, Elke Pogge, additional, Reiners, Katrin S, additional, Nolte, Ilja M, additional, Smedby, Karin E, additional, Adami, Hans-Olov, additional, Russell, Nicola S, additional, Glimelius, Bengt, additional, Hamilton-Dutoit, Stephen, additional, de Bruin, Marieke, additional, Ryder, Lars P, additional, Molin, Daniel, additional, Sorensen, Karina Meden, additional, Chang, Ellen T, additional, Taylor, Malcolm, additional, Cooke, Rosie, additional, Hofstra, Robert, additional, Westers, Helga, additional, van Wezel, Tom, additional, van Eijk, Ronald, additional, Ashworth, Alan, additional, Rostgaard, Klaus, additional, Melbye, Mads, additional, Swerdlow, Anthony J, additional, and Houlston, Richard S, additional

Published
2010
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48. Allergy and glioma risk: Test of association by genotype

Author

Dobbins, Sara E., primary, Hosking, Fay J., additional, Shete, Sanjay, additional, Armstrong, Georgina, additional, Swerdlow, Anthony, additional, Liu, Yanhong, additional, Yu, Robert, additional, Lau, Ching, additional, Schoemaker, Minouk J., additional, Hepworth, Sarah J., additional, Muir, Kenneth, additional, Bondy, Melissa, additional, and Houlston, Richard S., additional

Published
2010
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49. Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk

Author

Sherborne, Amy L, primary, Hosking, Fay J, additional, Prasad, Rashmi B, additional, Kumar, Rajiv, additional, Koehler, Rolf, additional, Vijayakrishnan, Jayaram, additional, Papaemmanuil, Elli, additional, Bartram, Claus R, additional, Stanulla, Martin, additional, Schrappe, Martin, additional, Gast, Andreas, additional, Dobbins, Sara E, additional, Ma, Yussanne, additional, Sheridan, Eamonn, additional, Taylor, Malcolm, additional, Kinsey, Sally E, additional, Lightfoot, Tracey, additional, Roman, Eve, additional, Irving, Julie A E, additional, Allan, James M, additional, Moorman, Anthony V, additional, Harrison, Christine J, additional, Tomlinson, Ian P, additional, Richards, Sue, additional, Zimmermann, Martin, additional, Szalai, Csaba, additional, Semsei, Ágnes F, additional, Erdelyi, Daniel J, additional, Krajinovic, Maja, additional, Sinnett, Daniel, additional, Healy, Jasmine, additional, Neira, Anna Gonzalez, additional, Kawamata, Norihiko, additional, Ogawa, Seishi, additional, Koeffler, H Phillip, additional, Hemminki, Kari, additional, Greaves, Mel, additional, and Houlston, Richard S, additional

Published
2010
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50. Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk

Author

Crowther-Swanepoel, Dalemari, primary, Broderick, Peter, additional, Di Bernardo, Maria Chiara, additional, Dobbins, Sara E, additional, Torres, María, additional, Mansouri, Mahmoud, additional, Ruiz-Ponte, Clara, additional, Enjuanes, Anna, additional, Rosenquist, Richard, additional, Carracedo, Angel, additional, Jurlander, Jesper, additional, Campo, Elias, additional, Juliusson, Gunnar, additional, Montserrat, Emilio, additional, Smedby, Karin E, additional, Dyer, Martin J S, additional, Matutes, Estella, additional, Dearden, Claire, additional, Sunter, Nicola J, additional, Hall, Andrew G, additional, Mainou-Fowler, Tryfonia, additional, Jackson, Graham H, additional, Summerfield, Geoffrey, additional, Harris, Robert J, additional, Pettitt, Andrew R, additional, Allsup, David J, additional, Bailey, James R, additional, Pratt, Guy, additional, Pepper, Chris, additional, Fegan, Chris, additional, Parker, Anton, additional, Oscier, David, additional, Allan, James M, additional, Catovsky, Daniel, additional, and Houlston, Richard S, additional

Published
2010
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