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734 results on '"Pittman, Alan"'

1. RNA Therapy for Oncogenic NRAS-Driven Nevi Induces Apoptosis

Author

Bryant, Dale, Barberan-Martin, Sara, Maeshima, Ruhina, del Valle Torres, Ignacio, Rabii, Mohammad, Baird, William, Sauvadet, Aimie, Demetriou, Charalambos, Jones, Phoebe, Knöpfel, Nicole, Michailidis, Fanourios, Riachi, Melissa, Bennett, Dorothy C., Zecchin, Davide, Pittman, Alan, Polubothu, Satyamaanasa, Hart, Stephen, and Kinsler, Veronica A.

Published
2025
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2. Mosaic BRAF Fusions Are a Recurrent Cause of Congenital Melanocytic Nevi Targetable by MAPK Pathway Inhibition

Author

Martin, Sara Barberan, Polubothu, Satyamaanasa, Bruzos, Alicia Lopez, Kelly, Gavin, Horswell, Stuart, Sauvadet, Aimie, Bryant, Dale, Zecchin, Davide, Riachi, Melissa, Michailidis, Fanourios, Sadri, Amir, Muwanga-Nanyonjo, Noreen, Lopez-Balboa, Pablo, Knöpfel, Nicole, Bulstrode, Neil, Pittman, Alan, Yeh, Iwei, and Kinsler, Veronica A.

Published
2024
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5. Biallelic variants in OGDH encoding oxoglutarate dehydrogenase lead to a neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities

Author

Whittle, Ella F., Chilian, Madison, Karimiani, Ehsan Ghayoor, Progri, Helga, Buhas, Daniela, Kose, Melis, Ganetzky, Rebecca D., Toosi, Mehran Beiraghi, Torbati, Paria Najarzadeh, Badv, Reza Shervin, Shelihan, Ivan, Yang, Hui, Elloumi, Houda Zghal, Lee, Sukyeong, Jamshidi, Yalda, Pittman, Alan M., Houlden, Henry, Ignatius, Erika, Rahman, Shamima, Maroofian, Reza, Yoon, Wan Hee, and Carroll, Christopher J.

Published
2023
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6. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author

Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki V., Hutri-Kähönen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J. Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O’Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome I., Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.

Published
2022
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7. Inherited duplications of PPP2R3B predispose to nevi and melanoma via a C21orf91-driven proliferative phenotype

Author

Polubothu, Satyamaanasa, Zecchin, Davide, Al-Olabi, Lara, Lionarons, Daniël A., Harland, Mark, Horswell, Stuart, Thomas, Anna C., Hunt, Lilian, Wlodarchak, Nathan, Aguilera, Paula, Brand, Sarah, Bryant, Dale, Carrera, Cristina, Chen, Hui, Elgar, Greg, Harwood, Catherine A., Howell, Michael, Larue, Lionel, Loughlin, Sam, MacDonald, Jeff, Malvehy, Josep, Barberan, Sara Martin, da Silva, Vanessa Martins, Molina, Miriam, Morrogh, Deborah, Moulding, Dale, Nsengimana, Jérémie, Pittman, Alan, Puig-Butillé, Joan-Anton, Parmar, Kiran, Sebire, Neil J., Scherer, Stephen, Stadnik, Paulina, Stanier, Philip, Tell, Gemma, Waelchli, Regula, Zarrei, Mehdi, Puig, Susana, Bataille, Véronique, Xing, Yongna, Healy, Eugene, Moore, Gudrun E., Di, Wei-Li, Newton-Bishop, Julia, Downward, Julian, and Kinsler, Veronica A.

Published
2021
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8. MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration

Author

Simone, Roberto, Javad, Faiza, Emmett, Warren, Wilkins, Oscar G., Almeida, Filipa Lourenço, Barahona-Torres, Natalia, Zareba-Paslawska, Justyna, Ehteramyan, Mazdak, Zuccotti, Paola, Modelska, Angelika, Siva, Kavitha, Virdi, Gurvir S., Mitchell, Jamie S., Harley, Jasmine, Kay, Victoria A., Hondhamuni, Geshanthi, Trabzuni, Daniah, Ryten, Mina, Wray, Selina, Preza, Elisavet, Kia, Demis A., Pittman, Alan, Ferrari, Raffaele, Manzoni, Claudia, Lees, Andrew, Hardy, John A., Denti, Michela A., Quattrone, Alessandro, Patani, Rickie, Svenningsson, Per, Warner, Thomas T., Plagnol, Vincent, Ule, Jernej, and de Silva, Rohan

Published
2021
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11. O09 Targeted genetic therapy for congenital melanocytic naevi

Author

Bryant, Dale, primary, Barberan-Martin, Sara, additional, Maeshima, Ruhina, additional, Del Valle Torres, Ignacio, additional, Rabii, Mohammad, additional, Sauvadet, Aimie, additional, Demetriou, Charalambos, additional, Knöpfel, Nicole, additional, Michailides, Fanis, additional, Riachi, Melissa, additional, Zecchin, Davide, additional, Pittman, Alan, additional, Polubothu, Satyamaanasa, additional, Hart, Steve, additional, and Kinsler, Veronica, additional

Published
2024
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12. Uniparental isodisomy of chromosome 2 causing MRPL44-related multisystem mitochondrial disease

Author

Horga, Alejandro, Manole, Andreea, Mitchell, Alice L., Bugiardini, Enrico, Hargreaves, Iain P., Mowafi, Walied, Bettencourt, Conceição, Blakely, Emma L., He, Langping, Polke, James M., Woodward, Catherine E., Dalla Rosa, Ilaria, Shah, Sachit, Pittman, Alan M., Quinlivan, Ros, Reilly, Mary M., Taylor, Robert W., Holt, Ian J., Hanna, Michael G., Pitceathly, Robert D. S., Spinazzola, Antonella, and Houlden, Henry

Published
2021
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13. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.

Author

van Rheenen, Wouter, Shatunov, Aleksey, Dekker, Annelot M, McLaughlin, Russell L, Diekstra, Frank P, Pulit, Sara L, van der Spek, Rick AA, Võsa, Urmo, de Jong, Simone, Robinson, Matthew R, Yang, Jian, Fogh, Isabella, van Doormaal, Perry Tc, Tazelaar, Gijs HP, Koppers, Max, Blokhuis, Anna M, Sproviero, William, Jones, Ashley R, Kenna, Kevin P, van Eijk, Kristel R, Harschnitz, Oliver, Schellevis, Raymond D, Brands, William J, Medic, Jelena, Menelaou, Androniki, Vajda, Alice, Ticozzi, Nicola, Lin, Kuang, Rogelj, Boris, Vrabec, Katarina, Ravnik-Glavač, Metka, Koritnik, Blaž, Zidar, Janez, Leonardis, Lea, Grošelj, Leja Dolenc, Millecamps, Stéphanie, Salachas, François, Meininger, Vincent, de Carvalho, Mamede, Pinto, Susana, Mora, Jesus S, Rojas-García, Ricardo, Polak, Meraida, Chandran, Siddharthan, Colville, Shuna, Swingler, Robert, Morrison, Karen E, Shaw, Pamela J, Hardy, John, Orrell, Richard W, Pittman, Alan, Sidle, Katie, Fratta, Pietro, Malaspina, Andrea, Topp, Simon, Petri, Susanne, Abdulla, Susanne, Drepper, Carsten, Sendtner, Michael, Meyer, Thomas, Ophoff, Roel A, Staats, Kim A, Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, Van Deerlin, Vivianna M, Trojanowski, John Q, Elman, Lauren, McCluskey, Leo, Basak, A Nazli, Tunca, Ceren, Hamzeiy, Hamid, Parman, Yesim, Meitinger, Thomas, Lichtner, Peter, Radivojkov-Blagojevic, Milena, Andres, Christian R, Maurel, Cindy, Bensimon, Gilbert, Landwehrmeyer, Bernhard, Brice, Alexis, Payan, Christine AM, Saker-Delye, Safaa, Dürr, Alexandra, Wood, Nicholas W, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Rietschel, Marcella, Cichon, Sven, Nöthen, Markus M, Amouyel, Philippe, Tzourio, Christophe, Dartigues, Jean-François, Uitterlinden, Andre G, Rivadeneira, Fernando, Estrada, Karol, Hofman, Albert, Curtis, Charles, and Blauw, Hylke M

Subjects
PARALS Registry, SLALOM Group, SLAP Registry, FALS Sequencing Consortium, SLAGEN Consortium, NNIPPS Study Group, Humans, Amyotrophic Lateral Sclerosis, Genetic Predisposition to Disease, Proteins, Cytoskeletal Proteins, Myelin Proteins, Case-Control Studies, Cohort Studies, Mutation, Netherlands, Munc18 Proteins, Genome-Wide Association Study, Neurosciences, Rare Diseases, Brain Disorders, Biotechnology, Prevention, Human Genome, Neurodegenerative, Genetics, ALS, Aetiology, 2.1 Biological and endogenous factors, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.

Published
2016

14. The Intellectual Disability Risk Gene Kdm5b Regulates Long-Term Memory Consolidation in the Hippocampus.

Author

Pérez-Sisqués, Leticia, Bhatt, Shail U., Matuleviciute, Rugile, Gileadi, Talia E., Kramar, Eniko, Graham, Andrew, Garcia, Franklin G., Keiser, Ashley, Matheos, Dina P., Cain, James A., Pittman, Alan M., Andreae, Laura C., Fernandes, Cathy, Wood, Marcelo A., Giese, K. Peter, and Basson, M. Albert

Subjects
LONG-term memory, HISTONE demethylases, INTELLECTUAL disabilities, GENE expression, COGNITIVE ability, AGENESIS of corpus callosum, RECESSIVE genes
Abstract

The histone lysine demethylase KDM5B is implicated in recessive intellectual disability disorders, and heterozygous, proteintruncating variants in KDM5B are associated with reduced cognitive function in the population. The KDM5 family of lysine demethylases has developmental and homeostatic functions in the brain, some of which appear to be independent of lysine demethylase activity. To determine the functions of KDM5B in hippocampus-dependent learning and memory, we first studied male and female mice homozygous for a Kdm5bΔARID allele that lacks demethylase activity. Kdm5bΔARID/ΔARID mice exhibited hyperactivity and long-term memory deficits in hippocampus-dependent learning tasks. The expression of immediate early, activity-dependent genes was downregulated in these mice and hyperactivated upon a learning stimulus compared with wild-type (WT) mice. A number of other learning-associated genes were also significantly dysregulated in the Kdm5bΔARID/ΔARID hippocampus. Next, we knocked down Kdm5b specifically in the adult, WT mouse hippocampus with shRNA. Kdm5b knockdown resulted in spontaneous seizures, hyperactivity, and hippocampus-dependent long-term memory and long-term potentiation deficits. These findings identify KDM5B as a critical regulator of gene expression and synaptic plasticity in the adult hippocampus and suggest that at least some of the cognitive phenotypes associated with KDM5B gene variants are caused by direct effects on memory consolidation mechanisms. [ABSTRACT FROM AUTHOR]

Published
2024
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17. 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

18. 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

19. Mosaic BRAF Fusions Are a Recurrent Cause of Congenital Melanocytic Nevi Targetable by MAPK Pathway Inhibition

Author

Martin, Sara Barberan, primary, Polubothu, Satyamaanasa, additional, Bruzos, Alicia Lopez, additional, Kelly, Gavin, additional, Horswell, Stuart, additional, Sauvadet, Aimie, additional, Bryant, Dale, additional, Zecchin, Davide, additional, Riachi, Melissa, additional, Michailidis, Fanourios, additional, Sadri, Amir, additional, Muwanga-Nanyonjo, Noreen, additional, Lopez-Balboa, Pablo, additional, Knöpfel, Nicole, additional, Bulstrode, Neil, additional, Pittman, Alan, additional, Yeh, Iwei, additional, and Kinsler, Veronica A., additional

Published
2023
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20. Autosomal dominant optic atrophy and cataract “plus” phenotype including axonal neuropathy

Author

Horga, Alejandro, Bugiardini, Enrico, Manole, Andreea, Bremner, Fion, Jaunmuktane, Zane, Dankwa, Lois, Rebelo, Adriana P., Woodward, Catherine E., Hargreaves, Iain P., Cortese, Andrea, Pittman, Alan M., Brandner, Sebastian, Polke, James M., Pitceathly, Robert D.S., Züchner, Stephan, Hanna, Michael G., Scherer, Steven S., Houlden, Henry, and Reilly, Mary M.

Published
2019
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21. Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson’s disease

Author

Brown, Emmeline E., Blauwendraat, Cornelis, Trinh, Joanne, Rizig, Mie, Nalls, Mike A., Leveille, Etienne, Ruskey, Jennifer A., Jonvik, Hallgeir, Tan, Manuela M.X., Bandres-Ciga, Sara, Hassin-Baer, Sharon, Brockmann, Kathrin, Infante, Jon, Tolosa, Eduardo, Ezquerra, Mario, Ben Romdhan, Sawssan, Benmahdjoub, Mustapha, Arezki, Mohamed, Mhiri, Chokri, Hardy, John, Singleton, Andrew B., Alcalay, Roy N., Gasser, Thomas, Grosset, Donald G., Williams, Nigel M., Pittman, Alan, Gan-Or, Ziv, Fernandez-Santiago, Ruben, Brice, Alexis, Lesage, Suzanne, Farrer, Matthew, Wood, Nicholas, and Morris, Huw R.

Published
2021
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22. Biallelic variants in TSPOAP1, encoding the active-zone protein RIMBP1, cause autosomal recessive dystonia

Author

Mencacci, Niccolo E., Brockmann, Marisa M., Dai, Jinye, Pajusalu, Sander, Atasu, Burcu, Campos, Joaquin, Pino, Gabriela, Gonzalez-Latapi, Paulina, Patzke, Christopher, Schwake, Michael, Tucci, Arianna, Pittman, Alan, Simon-Sanchez, Javier, Carvill, Gemma L., Wiethoff, Bettina Balin Sarah, Warner, Thomas T., Papandreou, Apostolos, Soo, Audrey, Rein, Reet, Kadastik-Eerme, Liis, Puusepp, Sanna, Reinson, Karit, Tomberg, Tiiu, Hanagasi, Hasmet, Gasser, Thomas, Bhatia, Kailash P., Kurian, Manju A., Lohmann, Ebba, Ounap, Katrin, Rosenmund, Christian, Sudhof, Thomas C., Wood, Nicholas W., Krainc, Dimitri, and Acuna, Claudio

Subjects
Binding proteins -- Health aspects, Neural transmission -- Genetic aspects -- Health aspects, Genetic variation -- Health aspects, Dystonia -- Genetic aspects -- Development and progression -- Care and treatment, Health care industry
Abstract

Dystonia is a debilitating hyperkinetic movement disorder, which can be transmitted as a monogenic trait. Here, we describe homozygous frameshift, nonsense, and missense variants in TSPOAP1, which encodes the active-zone RIM-binding protein 1 (RIMBP1), as a genetic cause of autosomal recessive dystonia in 7 subjects from 3 unrelated families. Subjects carrying loss-of-function variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy. Conversely, subjects carrying a pathogenic missense variant (p.Gly1808Ser) presented with isolated adult-onset focal dystonia. In mice, complete loss of RIMBP1, known to reduce neurotransmission, led to motor abnormalities reminiscent of dystonia, decreased Purkinje cell dendritic arborization, and reduced numbers of cerebellar synapses. In vitro analysis of the p.Gly1808Ser variant showed larger spike-evoked calcium transients and enhanced neurotransmission, suggesting that RIMBP1-linked dystonia can be caused by either reduced or enhanced rates of spike-evoked release in relevant neural networks. Our findings establish a direct link between dysfunction of the presynaptic active zone and dystonia and highlight the critical role played by well-balanced neurotransmission in motor control and disease pathogenesis., Introduction Dystonia is a disabling hyperkinetic movement disorder characterized by an excess of sustained, often repetitive, involuntary twisting movements, and abnormal postures (1). Dystonia, after Parkinson's disease and essential tremor, [...]

Published
2021
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23. Genetic Insights from Consanguineous Cardiomyopathy Families

Author

Maurer, Constance, primary, Boleti, Olga, additional, Najarzadeh Torbati, Paria, additional, Norouzi, Farzaneh, additional, Fowler, Anna Nicole Rebekah, additional, Minaee, Shima, additional, Salih, Khalid Hama, additional, Taherpour, Mehdi, additional, Birjandi, Hassan, additional, Alizadeh, Behzad, additional, Salih, Aso Faeq, additional, Bijari, Moniba, additional, Houlden, Henry, additional, Pittman, Alan Michael, additional, Maroofian, Reza, additional, Almashham, Yahya H., additional, Karimiani, Ehsan Ghayoor, additional, Kaski, Juan Pablo, additional, Faqeih, Eissa Ali, additional, Vakilian, Farveh, additional, and Jamshidi, Yalda, additional

Published
2023
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24. 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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25. Integrin α7 Mutations Are Associated With Adult‐Onset Cardiac Dysfunction in Humans and Mice

Author

Bugiardini, Enrico, primary, Nunes, Andreia M., additional, Oliveira‐Santos, Ariany, additional, Dagda, Marisela, additional, Fontelonga, Tatiana M., additional, Barraza‐Flores, Pamela, additional, Pittman, Alan M., additional, Morrow, Jasper M., additional, Parton, Matthew, additional, Houlden, Henry, additional, Elliott, Perry M., additional, Syrris, Petros, additional, Maas, Roderick P., additional, Akhtar, Mohammed M., additional, Küsters, Benno, additional, Raaphorst, Joost, additional, Schouten, Meyke, additional, Kamsteeg, Erik‐Jan, additional, van Engelen, Baziel, additional, Hanna, Michael G., additional, Phadke, Rahul, additional, Lopes, Luis R., additional, Matthews, Emma, additional, and Burkin, Dean J., additional

Published
2022
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27. Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at 16q11.2 and MAPT H1 loci

Author

Soutar, Marc P M, primary, Melandri, Daniela, additional, O’Callaghan, Benjamin, additional, Annuario, Emily, additional, Monaghan, Amy E, additional, Welsh, Natalie J, additional, D’Sa, Karishma, additional, Guelfi, Sebastian, additional, Zhang, David, additional, Pittman, Alan, additional, Trabzuni, Daniah, additional, Verboven, Anouk H A, additional, Pan, Kylie S, additional, Kia, Demis A, additional, Bictash, Magda, additional, Gandhi, Sonia, additional, Houlden, Henry, additional, Cookson, Mark R, additional, Kasri, Nael Nadif, additional, Wood, Nicholas W, additional, Singleton, Andrew B, additional, Hardy, John, additional, Whiting, Paul J, additional, Blauwendraat, Cornelis, additional, Whitworth, Alexander J, additional, Manzoni, Claudia, additional, Ryten, Mina, additional, Lewis, Patrick A, additional, and Plun-Favreau, Hélène, additional

Published
2022
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28. Rare Variation in Drug Metabolism and Long QT Genes and the Genetic Susceptibility to Acquired Long QT Syndrome

Author

Gray, Belinda, Baruteau, Alban-Elouen, Antolin, Albert A, Pittman, Alan, Sarganas, Giselle, Molokhia, Mariam, Blom, Marieke T, Bastiaenen, Rachel, Bardai, Abdenasser, Priori, Silvia G, Napolitano, Carlo, Weeke, Peter E, Shakir, Saad A, Haverkamp, Wilhelm, Mestres, Jordi, Winkel, Bo, Witney, Adam A, Chis-Ster, Irina, Sangaralingam, Ajanthah, Camm, A John, Tfelt-Hansen, Jacob, Roden, Dan M, Tan, Hanno L, Garbe, Edeltraut, Sturkenboom, Miriam, Behr, Elijah R, Gray, Belinda, Baruteau, Alban-Elouen, Antolin, Albert A, Pittman, Alan, Sarganas, Giselle, Molokhia, Mariam, Blom, Marieke T, Bastiaenen, Rachel, Bardai, Abdenasser, Priori, Silvia G, Napolitano, Carlo, Weeke, Peter E, Shakir, Saad A, Haverkamp, Wilhelm, Mestres, Jordi, Winkel, Bo, Witney, Adam A, Chis-Ster, Irina, Sangaralingam, Ajanthah, Camm, A John, Tfelt-Hansen, Jacob, Roden, Dan M, Tan, Hanno L, Garbe, Edeltraut, Sturkenboom, Miriam, and Behr, Elijah R

Abstract

BACKGROUND: Acquired long QT syndrome (aLQTS) is a serious unpredictable adverse drug reaction. Pharmacogenomic markers may predict risk.METHODS: Among 153 aLQTS patients (mean age 58 years [range, 14-88], 98.7% White, 85.6% symptomatic), computational methods identified proteins interacting most significantly with 216 QT-prolonging drugs. All cases underwent sequencing of 31 candidate genes arising from this analysis or associating with congenital LQTS. Variants were filtered using a minor allele frequency <1% and classified for susceptibility for aLQTS. Gene-burden analyses were then performed comparing the primary cohort to control exomes (n=452) and an independent replication aLQTS exome sequencing cohort.RESULTS: In 25.5% of cases, at least one rare variant was identified: 22.2% of cases carried a rare variant in a gene associated with congenital LQTS, and in 4% of cases that variant was known to be pathogenic or likely pathogenic for congenital LQTS; 7.8% cases carried a cytochrome-P450 (CYP) gene variant. Of 12 identified CYP variants, 11 (92%) were in an enzyme known to metabolize at least one culprit drug to which the subject had been exposed. Drug-drug interactions that affected culprit drug metabolism were found in 19% of cases. More than one congenital LQTS variant, CYP gene variant, or drug interaction was present in 7.8% of cases. Gene-burden analyses of the primary cohort compared to control exomes (n=452), and an independent replication aLQTS exome sequencing cohort (n=67) and drug-tolerant controls (n=148) demonstrated an increased burden of rare (minor allele frequency<0.01) variants in CYP genes but not LQTS genes.CONCLUSIONS: Rare susceptibility variants in CYP genes are emerging as potentially important pharmacogenomic risk markers for aLQTS and could form part of personalized medicine approaches in the future.

Published
2022

29. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author

Arts-assistenten Kinderen, Gezonde Vaten, Circulatory Health, Team Medisch, Young, William J, Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A, Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E, Weiss, Stefan, Baldassari, Antoine R, Bartz, Traci M, Cook, James P, Evans, Daniel S, Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L, Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A, Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R, Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C, Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J, Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T, Felix, Stephan B, Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Huang, Paul L, Huikuri, Heikki V, Hutri-Kähönen, Nina, Ikram, M Arfan, Jackson, Rebecca D, Junttila, Juhani, Kavousi, Maryam, Kors, Jan A, Leal, Thiago P, Lemaitre, Rozenn N, Lin, Henry J, Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W, Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P, Mitchell, Rebecca N, Mononen, Nina, Montasser, May E, Morrison, Alanna C, Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K, Pelliccione, Giulia, Pittman, Alan, Porteous, David J, Pramstaller, Peter P, Preuss, Michael H, Raitakari, Olli T, Reiner, Alexander P, Ribeiro, Antonio Luiz P, Rice, Kenneth M, Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M Benjamin, Sinagra, Gianfranco, Sinner, Moritz F, Soliman, Elsayed Z, Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A, Wilson, James G, Avery, Christy L, Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J F, Lubitz, Steven A, Mook-Kanamori, Dennis O, Morris, Andrew P, O'Connell, Jeffrey R, Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M, Rotter, Jerome I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James F, Arking, Dan E, Ramirez, Julia, Lambiase, Pier D, Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B, Arts-assistenten Kinderen, Gezonde Vaten, Circulatory Health, Team Medisch, Young, William J, Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A, Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E, Weiss, Stefan, Baldassari, Antoine R, Bartz, Traci M, Cook, James P, Evans, Daniel S, Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L, Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A, Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R, Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C, Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J, Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T, Felix, Stephan B, Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Huang, Paul L, Huikuri, Heikki V, Hutri-Kähönen, Nina, Ikram, M Arfan, Jackson, Rebecca D, Junttila, Juhani, Kavousi, Maryam, Kors, Jan A, Leal, Thiago P, Lemaitre, Rozenn N, Lin, Henry J, Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W, Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P, Mitchell, Rebecca N, Mononen, Nina, Montasser, May E, Morrison, Alanna C, Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K, Pelliccione, Giulia, Pittman, Alan, Porteous, David J, Pramstaller, Peter P, Preuss, Michael H, Raitakari, Olli T, Reiner, Alexander P, Ribeiro, Antonio Luiz P, Rice, Kenneth M, Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M Benjamin, Sinagra, Gianfranco, Sinner, Moritz F, Soliman, Elsayed Z, Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A, Wilson, James G, Avery, Christy L, Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J F, Lubitz, Steven A, Mook-Kanamori, Dennis O, Morris, Andrew P, O'Connell, Jeffrey R, Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M, Rotter, Jerome I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James F, Arking, Dan E, Ramirez, Julia, Lambiase, Pier D, Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B

Published
2022

30. Rare Variation in Drug Metabolism and Long QT Genes and the Genetic Susceptibility to Acquired Long QT Syndrome

Author

Data Science & Biostatistiek, Child Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Gray, Belinda, Baruteau, Alban-Elouen, Antolin, Albert A, Pittman, Alan, Sarganas, Giselle, Molokhia, Mariam, Blom, Marieke T, Bastiaenen, Rachel, Bardai, Abdenasser, Priori, Silvia G, Napolitano, Carlo, Weeke, Peter E, Shakir, Saad A, Haverkamp, Wilhelm, Mestres, Jordi, Winkel, Bo, Witney, Adam A, Chis-Ster, Irina, Sangaralingam, Ajanthah, Camm, A John, Tfelt-Hansen, Jacob, Roden, Dan M, Tan, Hanno L, Garbe, Edeltraut, Sturkenboom, Miriam, Behr, Elijah R, Data Science & Biostatistiek, Child Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Gray, Belinda, Baruteau, Alban-Elouen, Antolin, Albert A, Pittman, Alan, Sarganas, Giselle, Molokhia, Mariam, Blom, Marieke T, Bastiaenen, Rachel, Bardai, Abdenasser, Priori, Silvia G, Napolitano, Carlo, Weeke, Peter E, Shakir, Saad A, Haverkamp, Wilhelm, Mestres, Jordi, Winkel, Bo, Witney, Adam A, Chis-Ster, Irina, Sangaralingam, Ajanthah, Camm, A John, Tfelt-Hansen, Jacob, Roden, Dan M, Tan, Hanno L, Garbe, Edeltraut, Sturkenboom, Miriam, and Behr, Elijah R

Published
2022

33. Rare Variation in Drug Metabolism and Long QT Genes and the Genetic Susceptibility to Acquired Long QT Syndrome

Author

Gray, Belinda, primary, Baruteau, Alban-Elouen, additional, Antolin, Albert A., additional, Pittman, Alan, additional, Sarganas, Giselle, additional, Molokhia, Mariam, additional, Blom, Marieke T., additional, Bastiaenen, Rachel, additional, Bardai, Abdenasser, additional, Priori, Silvia G., additional, Napolitano, Carlo, additional, Weeke, Peter E., additional, Shakir, Saad A., additional, Haverkamp, Wilhelm, additional, Mestres, Jordi, additional, Winkel, Bo, additional, Witney, Adam A., additional, Chis-Ster, Irina, additional, Sangaralingam, Ajanthah, additional, Camm, A. John, additional, Tfelt-Hansen, Jacob, additional, Roden, Dan M., additional, Tan, Hanno L., additional, Garbe, Edeltraut, additional, Sturkenboom, Miriam, additional, and Behr, Elijah R., additional

Published
2022
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34. CHCHD10 Pro34Ser is not a highly penetrant pathogenic variant for amyotrophic lateral sclerosis and frontotemporal dementia

Author

Abdelkarim, Samir, Morgan, Sarah, Plagnol, Vincent, Lu, Ching-Hua, Adamson, Gary, Howard, Robin, Malaspina, Andrea, Orrell, Richard, Sharma, Nikhil, Sidle, Katie, Clarke, Jan, Fox, Nick C., Rossor, Martin N., Warren, Jason D., Clark, Camilla N., Rohrer, Jonathan D., Fisher, Elizabeth M. C., Mead, Simon, Pittman, Alan, and Fratta, Pietro

Published
2016
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36. Genetic analyses of the QT interval and its components in over 250K individuals identifies new loci and pathways affecting ventricular depolarization and repolarization

Author

Young, William J., primary, Lahrouchi, Najim, additional, Isaacs, Aaron, additional, Duong, ThuyVy, additional, Foco, Luisa, additional, Ahmed, Farah, additional, Brody, Jennifer A., additional, Salman, Reem, additional, Noordam, Raymond, additional, Benjamins, Jan-Walter, additional, Haessler, Jeffrey, additional, Lyytikäinen, Leo-Pekka, additional, Repetto, Linda, additional, Concas, Maria Pina, additional, van den Berg, Marten E., additional, Weiss, Stefan, additional, Baldassari, Antoine R., additional, Bartz, Traci M., additional, Cook, James P., additional, Evans, Daniel S., additional, Freudling, Rebecca, additional, Hines, Oliver, additional, Isaksen, Jonas L., additional, Lin, Honghuang, additional, Mei, Hao, additional, Moscati, Arden, additional, Müller-Nurasyid, Martina, additional, Nursyifa, Casia, additional, Qian, Yong, additional, Richmond, Anne, additional, Roselli, Carolina, additional, Ryan, Kathleen A., additional, Tarazona-Santos, Eduardo, additional, Thériault, Sébastien, additional, van Duijvenboden, Stefan, additional, Warren, Helen R., additional, Yao, Jie, additional, Raza, Dania, additional, Aeschbacher, Stefanie, additional, Ahlberg, Gustav, additional, Alonso, Alvaro, additional, Andreasen, Laura, additional, Bis, Joshua C., additional, Boerwinkle, Eric, additional, Campbell, Archie, additional, Catamo, Eulalia, additional, Cocca, Massimiliano, additional, Cutler, Michael J., additional, Darbar, Dawood, additional, De Grandi, Alessandro, additional, De Luca, Antonio, additional, Ding, Jun, additional, Ellervik, Christina, additional, Ellinor, Patrick T., additional, Felix, Stephan B., additional, Froguel, Philippe, additional, Fuchsberger, Christian, additional, Gögele, Martin, additional, Graff, Claus, additional, Graff, Mariaelisa, additional, Guo, Xiuqing, additional, Hansen, Torben, additional, Heckbert, Susan R., additional, Huang, Paul L., additional, Huikuri, Heikki V., additional, Hutri-Kähönen, Nina, additional, Ikram, M.Arfan, additional, Jackson, Rebecca D., additional, Junttila, Juhani, additional, Kavousi, Maryam, additional, Kors, Jan A., additional, Leal, Thiago P., additional, Lemaitre, Rozenn N., additional, Lin, Henry J., additional, Lind, Lars, additional, Linneberg, Allan, additional, Liu, Simin, additional, MacFarlane, Peter W., additional, Mangino, Massimo, additional, Meitinger, Thomas, additional, Mezzavilla, Massimo, additional, Mishra, Pashupati P., additional, Mitchell, Rebecca N., additional, Mononen, Nina, additional, Montasser, May E., additional, Morrison, Alanna C., additional, Nauck, Matthias, additional, Nauffal, Victor, additional, Navarro, Pau, additional, Nikus, Kjell, additional, Pare, Guillaume, additional, Patton, Kristen K., additional, Pelliccione, Giulia, additional, Pittman, Alan, additional, Porteous, David J., additional, Pramstaller, Peter P., additional, Preuss, Michael H., additional, Raitakari, Olli T., additional, Reiner, Alexander P., additional, Ribeiro, Antonio Luiz P., additional, Rice, Kenneth M., additional, Risch, Lorenz, additional, Schlessinger, David, additional, Schotten, Ulrich, additional, Schurmann, Claudia, additional, Shen, Xia, additional, Shoemaker, M.Benjamin, additional, Sinagra, Gianfranco, additional, Sinner, Moritz F., additional, Soliman, Elsayed Z., additional, Stoll, Monika, additional, Strauch, Konstantin, additional, Tarasov, Kirill, additional, Taylor, Kent D., additional, Tinker, Andrew, additional, Trompet, Stella, additional, Uitterlinden, André, additional, Völker, Uwe, additional, Völzke, Henry, additional, Waldenberger, Melanie, additional, Weng, Lu-Chen, additional, Whitsel, Eric A., additional, Wilson, James G., additional, Avery, Christy L., additional, Conen, David, additional, Correa, Adolfo, additional, Cucca, Francesco, additional, Dörr, Marcus, additional, Gharib, Sina A., additional, Girotto, Giorgia, additional, Grarup, Niels, additional, Hayward, Caroline, additional, Jamshidi, Yalda, additional, Järvelin, Marjo-Riitta, additional, Jukema, J.Wouter, additional, Kääb, Stefan, additional, Kähönen, Mika, additional, Kanters, Jørgen K., additional, Kooperberg, Charles, additional, Lehtimäki, Terho, additional, Lima-Costa, Maria Fernanda, additional, Liu, Yongmei, additional, Loos, Ruth J.F., additional, Lubitz, Steven A., additional, Mook-Kanamori, Dennis O., additional, Morris, Andrew P., additional, O’Connell, Jeffrey R., additional, Olesen, Morten Salling, additional, Orini, Michele, additional, Padmanabhan, Sandosh, additional, Pattaro, Cristian, additional, Peters, Annette, additional, Psaty, Bruce M., additional, Rotter, Jerome I., additional, Stricker, Bruno, additional, van der Harst, Pim, additional, van Duijn, Cornelia M., additional, Verweij, Niek, additional, Wilson, James F., additional, Arking, Dan E., additional, Ramirez, Julia, additional, Lambiase, Pier D., additional, Sotoodehnia, Nona, additional, Mifsud, Borbala, additional, Newton-Cheh, Christopher, additional, and Munroe, Patricia B., additional

Published
2021
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41. Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis

Author

Hanna, Michael G., Houlden, Henry, Machado, Pedro M., Gang, Qiang, Bettencourt, Conceicao, Healy, Estelle, Parton, Matthew, Holton, Janice L., Brady, Stefen, Hilton-Jones, David, Shieh, Perry B., Zanoteli, Edmar, de Camargo, Leonardo Valente, De Paepe, Boel, De Bleecker, Jan, Shaibani, Aziz, Ripolone, Michela, Violano, Raffaella, Moggio, Maurizio, Barohn, Richard J., Dimachkie, Mazen M., McVey, April L., Pasnoor, Mamatha, Glenn, Melanie, Jawdat, Omar, Statland, Jeffrey, Rico, Gabrielle, Mora, Marina, Mantegazza, Renato, Zanotti, Simona, Needham, Merrilee, Mastaglia, Frank, Liang, Christina, Dalakas, Marinos C., Biba, Angie, Chinoy, Hector, Lilleker, James B., Lamb, Janine, Platt, Hazel, Cooper, Robert G., Miller, James A.L., Roberts, Mark, Househam, Elizabeth, Hilton, David, Shivane, Aditya, Bartlett, Amy, Kissel, John T., Runk, Heidi, Wicklund, Matthew, Saperstein, David S., McKinney, Lynette R., Bettencourt, Conceição, Pittman, Alan M., Hughes, Deborah, and Singleton, Andrew B.

Published
2016
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42. Mitochondrial DNA analysis from exome sequencing data improves diagnostic yield in neurological diseases

Author

Poole, Olivia V, Pizzamiglio, Chiara, Murphy, David, Falabella, Micol, Macken, William L, Bugiardini, Enrico, Woodward, Cathy E, Labrum, Robyn, Efthymiou, Stephanie, Salpietro, Vincenzo, Chelban, Viorica, Kaiyrzhanov, Rauan, Maroofian, Reza, Synaps, Group, Aguennouz, M'Hammed, Di Rosa, Gabriella, Amato, Anthony A, Gregory, Allison, Hayflick, Susan J, Jonvik, Hallgeir, Wood, Nicholas, Houlden, Henry, Vandrovcova, Jana, Hanna, Michael G, Pittman, Alan, and Pitceathly, Robert D S

Subjects
Adult, Male, 0301 basic medicine, Mitochondrial DNA, Mitochondrial Diseases, Adolescent, Disease, Brief Communication, DNA, Mitochondrial, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Exome Sequencing, Humans, Medicine, Exome sequencing, Aged, Aged, 80 and over, Genetics, business.industry, Middle Aged, Phenotype, Mtdna mutations, 030104 developmental biology, Neurology, Child, Preschool, Neurology (clinical), Nervous System Diseases, Brief Communications, business, 030217 neurology & neurosurgery
Abstract

A rapidly expanding catalog of neurogenetic disorders has encouraged a diagnostic shift towards early clinical whole exome sequencing (WES). Adult primary mitochondrial diseases (PMDs) frequently exhibit neurological manifestations that overlap with other nervous system disorders. However, mitochondrial DNA (mtDNA) is not routinely analyzed in standard clinical WES bioinformatic pipelines. We reanalyzed 11,424 exomes, enriched with neurological diseases, for pathogenic mtDNA variants. Twenty-four different mtDNA mutations were detected in 64 exomes, 11 of which were considered disease causing based on the associated clinical phenotypes. These findings highlight the diagnostic uplifts gained by analyzing mtDNA from WES data in neurological diseases. ANN NEUROL 2021;89:1240-1247.

Published
2021

44. Genetic analyses of the QT interval and its components in over 250K individuals identifies new loci and pathways affecting ventricular depolarization and repolarization

Author

Young, William J, Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A, Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E, Weiss, Stefan, Baldassari, Antoine R, Bartz, Traci M, Cook, James P, Evans, Daniel S, Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L, Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A, Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R, Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C, Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J, Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T, Felix, Stephan B, Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Huang, Paul L, Huikuri, Heikki V, Hutri-Kähönen, Nina, Ikram, M Arfan, Jackson, Rebecca D, Junttila, Juhani, Kavousi, Maryam, Kors, Jan A, Leal, Thiago P, Lemaitre, Rozenn N, Lin, Henry J, Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W, Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P, Mitchell, Rebecca N, Mononen, Nina, Montasser, May E, Morrison, Alanna C, Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K, Pelliccione, Giulia, Pittman, Alan, Porteous, David J, Pramstaller, Peter P, Preuss, Michael H, Raitakari, Olli T, Reiner, Alexander P, Ribeiro, Antonio Luiz P, Rice, Kenneth M, Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M Benjamin, Sinagra, Gianfranco, Sinner, Moritz F, Soliman, Elsayed Z, Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A, Wilson, James G, Avery, Christy L, Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J.F, Lubitz, Steven A, Mook-Kanamori, Dennis O, Morris, Andrew P, O'Connell, Jeffrey R, Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M, Rotter, Jerome I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James F, Arking, Dan E, Ramírez, Julia, Lambiase, Pier D, Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B

Subjects
genetic and genomic medicine, cardiovascular system, cardiovascular diseases
Abstract

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization (QRS duration) and repolarization (JT interval). Abnormalities of the QT interval are associated with potentially fatal ventricular arrhythmia. We conducted genome-wide multi-ancestry analyses in >250,000 individuals and identified 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identified associations with Mendelian disease genes. Enrichments were observed in established pathways for QT and JT, with new genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast, connective tissue components and processes for cell growth and extracellular matrix interactions were significantly enriched for QRS. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlighted potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

Published
2021
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45. Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers

Author

Mencacci, Niccolò E., Isaias, Ioannis U., Reich, Martin M., Ganos, Christos, Plagnol, Vincent, Polke, James M., Bras, Jose, Hersheson, Joshua, Stamelou, Maria, Pittman, Alan M., Noyce, Alastair J., Mok, Kin Y., Opladen, Thomas, Kunstmann, Erdmute, Hodecker, Sybille, Münchau, Alexander, Volkmann, Jens, Samnick, Samuel, Sidle, Katie, Nanji, Tina, Sweeney, Mary G., Houlden, Henry, Batla, Amit, Zecchinelli, Anna L., Pezzoli, Gianni, Marotta, Giorgio, Lees, Andrew, Alegria, Paulo, Krack, Paul, Cormier-Dequaire, Florence, Lesage, Suzanne, Brice, Alexis, Heutink, Peter, Gasser, Thomas, Lubbe, Steven J., Morris, Huw R., Taba, Pille, Koks, Sulev, Majounie, Elisa, Raphael Gibbs, J., Singleton, Andrew, Hardy, John, Klebe, Stephan, Bhatia, Kailash P., and Wood, Nicholas W.

Published
2014
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46. A 6.4 Mb Duplication of the α-Synuclein Locus Causing Frontotemporal Dementia and Parkinsonism: Phenotype-Genotype Correlations

Author

Kara, Eleanna, Kiely, Aoife P., Proukakis, Christos, Giffin, Nicola, Love, Seth, Hehir, Jason, Rantell, Khadija, Pandraud, Amelie, Hernandez, Dena G., Nacheva, Elizabeth, Pittman, Alan M., Nalls, Mike A., Singleton, Andrew B., Revesz, Tamas, Bhatia, Kailash P., Quinn, Niall, Hardy, John, Holton, Janice L., and Houlden, Henry

Published
2014
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48. Iterative Reanalysis of Hypertrophic Cardiomyopathy Exome Data Reveals Causative Pathogenic Mitochondrial DNA Variants

Author

Lopes, Luis R., primary, Murphy, David, additional, Bugiardini, Enrico, additional, Salem, Reem, additional, Jager, Joanna, additional, Futema, Marta, additional, Majid Akhtar, Mohammed, additional, Savvatis, Konstantinos, additional, Woodward, Cathy, additional, Pittman, Alan M., additional, Hanna, Michael G., additional, Syrris, Petros, additional, Pitceathly, Robert D.S., additional, and Elliott, Perry M., additional

Published
2021
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49. Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion

Author

Fratta, Pietro, Polke, James M., Newcombe, Jia, Mizielinska, Sarah, Lashley, Tammaryn, Poulter, Mark, Beck, Jon, Preza, Elisavet, Devoy, Anny, Sidle, Katie, Howard, Robin, Malaspina, Andrea, Orrell, Richard W., Clarke, Jan, Lu, Ching-Hua, Mok, Kin, Collins, Toby, Shoaii, Maryam, Nanji, Tina, Wray, Selina, Adamson, Gary, Pittman, Alan, Renton, Alan E., Traynor, Bryan J., Sweeney, Mary G., Revesz, Tamas, Houlden, Henry, Mead, Simon, Isaacs, Adrian M., and Fisher, Elizabeth M.C.

Published
2015
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50. Defective phosphatidylethanolamine biosynthesis leads to a broad ataxia-spasticity spectrum

Author

Kaiyrzhanov, Rauan, primary, Wortmann, Saskia, additional, Reid, Taryn, additional, Dehghani, Mohammadreza, additional, Vahidi Mehrjardi, Mohammad Yahya, additional, Alhaddad, Bader, additional, Wagner, Matias, additional, Deschauer, Marcus, additional, Cordts, Isabell, additional, Fernandez-Murray, J Pedro, additional, Treffer, Veronika, additional, Metanat, Zahra, additional, Pittman, Alan, additional, Houlden, Henry, additional, Meitinger, Thomas, additional, Carroll, Christopher, additional, McMaster, Christopher R, additional, and Maroofian, Reza, additional

Published
2021
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