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  1. Article ; Online: Valuation of opportunity costs by rats working for rewarding electrical brain stimulation.

    Rebecca Brana Solomon / Kent Conover / Peter Shizgal

    PLoS ONE, Vol 12, Iss 8, p e

    2017  Volume 0182120

    Abstract: Pursuit of one goal typically precludes simultaneous pursuit of another. Thus, each exclusive activity entails an "opportunity cost:" the forgone benefits from the next-best activity eschewed. The present experiment estimates, in laboratory rats, the ... ...

    Abstract Pursuit of one goal typically precludes simultaneous pursuit of another. Thus, each exclusive activity entails an "opportunity cost:" the forgone benefits from the next-best activity eschewed. The present experiment estimates, in laboratory rats, the function that maps objective opportunity costs into subjective ones. In an operant chamber, rewarding electrical brain stimulation was delivered when the cumulative time a lever had been depressed reached a criterion duration. The value of the activities forgone during this duration is the opportunity cost of the electrical reward. We determined which of four functions best describes how objective opportunity costs, expressed as the required duration of lever depression, are translated into their subjective equivalents. The simplest account is the identity function, which equates subjective and objective opportunity costs. A variant of this function called the "sigmoidal-slope function," converges on the identity function at longer durations but deviates from it at shorter durations. The sigmoidal-slope function has the form of a hockey stick. The flat "blade" denotes a range over which opportunity costs are subjectively equivalent; these durations are too short to allow substitution of more beneficial activities. The blade extends into an upward-curving portion over which costs become discriminable and finally into the straight "handle," over which objective and subjective costs match. The two remaining functions are based on hyperbolic and exponential temporal discounting, respectively. The results are best described by the sigmoidal-slope function. That this is so suggests that different principles of intertemporal choice are involved in the evaluation of time spent working for a reward or waiting for its delivery. The subjective opportunity-cost function plays a key role in the evaluation and selection of goals. An accurate description of its form and parameters is essential to successful modeling and prediction of instrumental performance and reward-related ...
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Valuation of opportunity costs by rats working for rewarding electrical brain stimulation.

    Solomon, Rebecca Brana / Conover, Kent / Shizgal, Peter

    PloS one

    2017  Volume 12, Issue 8, Page(s) e0182120

    Abstract: Pursuit of one goal typically precludes simultaneous pursuit of another. Thus, each exclusive activity entails an "opportunity cost:" the forgone benefits from the next-best activity eschewed. The present experiment estimates, in laboratory rats, the ... ...

    Abstract Pursuit of one goal typically precludes simultaneous pursuit of another. Thus, each exclusive activity entails an "opportunity cost:" the forgone benefits from the next-best activity eschewed. The present experiment estimates, in laboratory rats, the function that maps objective opportunity costs into subjective ones. In an operant chamber, rewarding electrical brain stimulation was delivered when the cumulative time a lever had been depressed reached a criterion duration. The value of the activities forgone during this duration is the opportunity cost of the electrical reward. We determined which of four functions best describes how objective opportunity costs, expressed as the required duration of lever depression, are translated into their subjective equivalents. The simplest account is the identity function, which equates subjective and objective opportunity costs. A variant of this function called the "sigmoidal-slope function," converges on the identity function at longer durations but deviates from it at shorter durations. The sigmoidal-slope function has the form of a hockey stick. The flat "blade" denotes a range over which opportunity costs are subjectively equivalent; these durations are too short to allow substitution of more beneficial activities. The blade extends into an upward-curving portion over which costs become discriminable and finally into the straight "handle," over which objective and subjective costs match. The two remaining functions are based on hyperbolic and exponential temporal discounting, respectively. The results are best described by the sigmoidal-slope function. That this is so suggests that different principles of intertemporal choice are involved in the evaluation of time spent working for a reward or waiting for its delivery. The subjective opportunity-cost function plays a key role in the evaluation and selection of goals. An accurate description of its form and parameters is essential to successful modeling and prediction of instrumental performance and reward-related decision making.
    MeSH term(s) Animals ; Brain/physiology ; Electric Stimulation ; Rats
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0182120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1.

    Chang, Christina C / Naranbhai, Vivek / Stern, Jared / Roche, Michael / Dantanarayana, Ashanti / Ke, Ruian / Tennakoon, Surekha / Solomon, Ajantha / Hoh, Rebecca / Hartogensis, Wendy / Hecht, Frederick M / Sikaris, Ken / Price, David J / Elliott, Julian H / Deeks, Steven G / Churchill, Melissa / Cameron, Paul U / Hengartner, Nicolas / Perelson, Alan S /
    Lewin, Sharon R

    AIDS (London, England)

    2018  Volume 32, Issue 15, Page(s) 2119–2128

    Abstract: Objective(s): To determine whether variation in cell-associated unspliced (CA-US) HIV RNA in HIV-infected individuals on antiretroviral therapy (ART) has a circadian basis.: Methods: Prospective observational study of HIV-infected individuals on ART. ...

    Abstract Objective(s): To determine whether variation in cell-associated unspliced (CA-US) HIV RNA in HIV-infected individuals on antiretroviral therapy (ART) has a circadian basis.
    Methods: Prospective observational study of HIV-infected individuals on ART. Blood was collected on three occasions and CA-US HIV RNA and mRNA of the circadian-locomotor-output-cycles-kaput (CLOCK)-associated genes quantified by real time PCR. CLOCK-associated proteins were over-expressed in a cell line stably transfected with an HIV long-terminal repeat (LTR) luciferase reporter.
    Results: Using a mixed effects model, there was a significant increase in log-CA-US RNA at the third visit compared with the first visit (effect size of 0.619 with standard error (SE) of 0.098, P < 0.001) and an independent effect of time of blood draw (effect size 0.051 (SE 0.025), P = 0.040). The CLOCK-associated gene, brain-and-muscle-ARNT-like-1 (BMAL-1) had a significant relationship with log CA-US HIV RNA (effect size 8.508 (SE 3.777), P = 0.028) and also with time (P = 0.045). Over expression of BMAL-1 and CLOCK in a cell line stably transfected with an HIV-LTR luciferase reporter resulted in an increase in luciferase expression and this was reduced following mutation of the second E-box in the HIV-LTR.
    Conclusion: The basal level of HIV transcription on ART can vary significantly and is modulated by the circadian regulator BMAL-1, amongst other factors.
    MeSH term(s) ARNTL Transcription Factors/biosynthesis ; ARNTL Transcription Factors/genetics ; Anti-Retroviral Agents/therapeutic use ; Blood Cells/virology ; Cells, Cultured ; Female ; Gene Expression Profiling ; HIV/growth & development ; HIV Infections/drug therapy ; HIV Infections/virology ; Host-Pathogen Interactions ; Humans ; Male ; Middle Aged ; RNA, Viral/analysis ; Real-Time Polymerase Chain Reaction ; Transcription, Genetic
    Chemical Substances ARNTL Transcription Factors ; BMAL1 protein, human ; Anti-Retroviral Agents ; RNA, Viral
    Language English
    Publishing date 2018-08-16
    Publishing country England
    Document type Clinical Trial ; Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 639076-6
    ISSN 1473-5571 ; 0269-9370 ; 1350-2840
    ISSN (online) 1473-5571
    ISSN 0269-9370 ; 1350-2840
    DOI 10.1097/QAD.0000000000001937
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Rociletinib in EGFR-mutated non-small-cell lung cancer.

    Sequist, Lecia V / Soria, Jean-Charles / Goldman, Jonathan W / Wakelee, Heather A / Gadgeel, Shirish M / Varga, Andrea / Papadimitrakopoulou, Vassiliki / Solomon, Benjamin J / Oxnard, Geoffrey R / Dziadziuszko, Rafal / Aisner, Dara L / Doebele, Robert C / Galasso, Cathy / Garon, Edward B / Heist, Rebecca S / Logan, Jennifer / Neal, Joel W / Mendenhall, Melody A / Nichols, Suzanne /
    Piotrowska, Zofia / Wozniak, Antoinette J / Raponi, Mitch / Karlovich, Chris A / Jaw-Tsai, Sarah / Isaacson, Jeffrey / Despain, Darrin / Matheny, Shannon L / Rolfe, Lindsey / Allen, Andrew R / Camidge, D Ross

    The New England journal of medicine

    2015  Volume 372, Issue 18, Page(s) 1700–1709

    Abstract: Background: Non-small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by the T790M EGFR mutation in most cases. Rociletinib ...

    Abstract Background: Non-small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by the T790M EGFR mutation in most cases. Rociletinib (CO-1686) is an EGFR inhibitor active in preclinical models of EGFR-mutated NSCLC with or without T790M.
    Methods: In this phase 1-2 study, we administered rociletinib to patients with EGFR-mutated NSCLC who had disease progression during previous treatment with an existing EGFR inhibitor. In the expansion (phase 2) part of the study, patients with T790M-positive disease received rociletinib at a dose of 500 mg twice daily, 625 mg twice daily, or 750 mg twice daily. Key objectives were assessment of safety, side-effect profile, pharmacokinetics, and preliminary antitumor activity of rociletinib. Tumor biopsies to identify T790M were performed during screening. Treatment was administered in continuous 21-day cycles.
    Results: A total of 130 patients were enrolled. The first 57 patients to be enrolled received the free-base form of rociletinib (150 mg once daily to 900 mg twice daily). The remaining patients received the hydrogen bromide salt (HBr) form (500 mg twice daily to 1000 mg twice daily). A maximum tolerated dose (the highest dose associated with a rate of dose-limiting toxic effects of less than 33%) was not identified. The only common dose-limiting adverse event was hyperglycemia. In an efficacy analysis that included patients who received free-base rociletinib at a dose of 900 mg twice daily or the HBr form at any dose, the objective response rate among the 46 patients with T790M-positive disease who could be evaluated was 59% (95% confidence interval [CI], 45 to 73), and the rate among the 17 patients with T790M-negative disease who could be evaluated was 29% (95% CI, 8 to 51).
    Conclusions: Rociletinib was active in patients with EGFR-mutated NSCLC associated with the T790M resistance mutation. (Funded by Clovis Oncology; ClinicalTrials.gov number, NCT01526928.).
    MeSH term(s) Acrylamides/administration & dosage ; Acrylamides/adverse effects ; Acrylamides/pharmacokinetics ; Aged ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm/genetics ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/genetics ; Female ; Humans ; Hyperglycemia/chemically induced ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/pharmacokinetics ; Pyrimidines/administration & dosage ; Pyrimidines/adverse effects ; Pyrimidines/pharmacokinetics
    Chemical Substances Acrylamides ; Antineoplastic Agents ; Protein Kinase Inhibitors ; Pyrimidines ; rociletinib (72AH61702G) ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2015-04-29
    Publishing country United States
    Document type Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMoa1413654
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

    Dejnirattisai, Wanwisa / Huo, Jiandong / Zhou, Daming / Zahradník, Jiří / Supasa, Piyada / Liu, Chang / Duyvesteyn, Helen M.E. / Ginn, Helen M. / Mentzer, Alexander J. / Tuekprakhon, Aekkachai / Nutalai, Rungtiwa / Wang, Beibei / Dijokaite, Aiste / Khan, Suman / Avinoam, Ori / Bahar, Mohammad / Skelly, Donal / Adele, Sandra / Johnson, Sile Ann /
    Amini, Ali / Ritter, Thomas G. / Mason, Chris / Dold, Christina / Pan, Daniel / Assadi, Sara / Bellass, Adam / Omo-Dare, Nicola / Koeckerling, David / Flaxman, Amy / Jenkin, Daniel / Aley, Parvinder K. / Voysey, Merryn / Clemens, Sue Ann Costa / Naveca, Felipe Gomes / Nascimento, Valdinete / Nascimento, Fernanda / Fernandes da Costa, Cristiano / Resende, Paola Cristina / Pauvolid-Correa, Alex / Siqueira, Marilda M. / Baillie, Vicky / Serafin, Natali / Kwatra, Gaurav / Da Silva, Kelly / Madhi, Shabir A. / Nunes, Marta C. / Malik, Tariq / Openshaw, Peter J.M. / Baillie, J. Kenneth / Semple, Malcolm G. / Townsend, Alain R. / Huang, Kuan-Ying A. / Tan, Tiong Kit / Carroll, Miles W. / Klenerman, Paul / Barnes, Eleanor / Dunachie, Susanna J. / Constantinides, Bede / Webster, Hermione / Crook, Derrick / Pollard, Andrew J. / Lambe, Teresa / Paterson, Neil G. / Williams, Mark A. / Hall, David R. / Fry, Elizabeth E. / Mongkolsapaya, Juthathip / Ren, Jingshan / Schreiber, Gideon / Stuart, David I. / Screaton, Gavin R. / Conlon, Christopher / Deeks, Alexandra S. / Frater, John / Frending, Lisa / Gardiner, Siobhan / Jämsén, Anni / Jeffery, Katie / Malone, Tom / Phillips, Eloise / Rothwell, Lucy / Stafford, Lizzie / Baillie, J Kenneth / Openshaw, Peter JM. / Carson, Gail / Alex, Beatrice / Andrikopoulos, Petros / Bach, Benjamin / Barclay, Wendy S. / Bogaert, Debby / Chand, Meera / Chechi, Kanta / Cooke, Graham S. / da Silva Filipe, Ana / de Silva, Thushan / Docherty, Annemarie B. / dos Santos Correia, Gonçalo / Dumas, Marc-Emmanuel / Dunning, Jake / Fletcher, Tom / Green, Christoper A. / Greenhalf, William / Griffin, Julian L. / Gupta, Rishi K. / Harrison, Ewen M. / Hiscox, Julian A. / Wai Ho, Antonia Ying / Horby, Peter W. / Ijaz, Samreen / Khoo, Saye / Law, Andrew / Lewis, Matthew R. / Liggi, Sonia / Lim, Wei Shen / Maslen, Lynn / Merson, Laura / Meynert, Alison M. / Moore, Shona C. / Noursadeghi, Mahdad / Olanipekun, Michael / Osagie, Anthonia / Palmarini, Massimo / Palmieri, Carlo / Paxton, William A. / Pollakis, Georgios / Price, Nicholas / Rambaut, Andrew / Robertson, Dave / Russell, Clark D. / Sancho-Shimizu, Vanessa / Sands, Caroline J. / Scott, Janet T. / Sigfrid, Louise / Solomon, Tom / Sriskandan, Shiranee / Stuart, David / Summers, Charlotte / Swann, Olivia V. / Takats, Zoltan / Takis, Panteleimon / Tedder, Richard S. / Thompson, AA Roger / Thomson, Emma C. / Thwaites, Ryan S. / Turtle, Lance CW. / Zambon, Maria / Hardwick, Hayley / Donohue, Chloe / Griffiths, Fiona / Oosthuyzen, Wilna / Donegan, Cara / Spencer, Rebecca G. / Norman, Lisa / Pius, Riinu / Drake, Thomas M. / Fairfield, Cameron J. / Knight, Stephen R. / Mclean, Kenneth A. / Murphy, Derek / Shaw, Catherine A. / Dalton, Jo / Girvan, Michelle / Saviciute, Egle / Roberts, Stephanie / Harrison, Janet / Marsh, Laura / Connor, Marie / Halpin, Sophie / Jackson, Clare / Gamble, C. / Plotkin, Daniel / Lee, James / Leeming, Gary / Wham, Murray / Clohisey, Sara / Hendry, Ross / Scott-Brown, Jas / Shaw, Victoria / McDonald, Sarah E. / Keating, Seán / Ahmed, Katie A. / Armstrong, Jane A. / Ashworth, Milton / Asiimwe, Innocent G. / Bakshi, Siddharth / Barlow, Samantha L. / Booth, Laura / Brennan, Benjamin / Bullock, Katie / Catterall, Benjamin WA. / Clark, Jordan J. / Clarke, Emily A. / Cole, Sarah / Cooper, Louise / Cox, Helen / Davis, Christopher / Dincarslan, Oslem / Dunn, Chris / Dyer, Philip / Elliott, Angela / Evans, Anthony / Finch, Lorna / Fisher, Lewis WS. / Foster, Terry / Garcia-Dorival, Isabel / Gunning, Philip / Hartley, Catherine / Jensen, Rebecca L. / Jones, Christopher B. / Jones, Trevor R. / Khandaker, Shadia / King So, Katharine / Kiy, Robyn T. / Koukorava, Chrysa / Lake, Annette / Lant, Suzannah / Latawiec, Diane / Lavelle-Langham, Lara / Lefteri, Daniella / Lett, Lauren / Livoti, Lucia A. / Mancini, Maria / McDonald, Sarah / McEvoy, Laurence / McLauchlan, John / Metelmann, Soeren / Miah, Nahida S. / Middleton, Joanna / Mitchell, Joyce / Murphy, Ellen G. / Penrice-Randal, Rebekah / Pilgrim, Jack / Prince, Tessa / Reynolds, Will / Ridley, P. Matthew / Sales, Debby / Shaw, Victoria E. / Shears, Rebecca K. / Small, Benjamin / Subramaniam, Krishanthi S. / Szemiel, Agnieska / Taggart, Aislynn / Tanianis-Hughes, Jolanta / Thomas, Jordan / Trochu, Erwan / van Tonder, Libby / Wilcock, Eve / Zhang, J. Eunice / Flaherty, Lisa / Maziere, Nicole / Cass, Emily / Carracedo, Alejandra Doce / Carlucci, Nicola / Holmes, Anthony / Massey, Hannah / Murphy, Lee / McCafferty, Sarah / Clark, Richard / Fawkes, Angie / Morrice, Kirstie / Maclean, Alan / Wrobel, Nicola / Donnelly, Lorna / Coutts, Audrey / Hafezi, Katarzyna / MacGillivray, Louise / Gilchrist, Tammy / Adeniji, Kayode / Agranoff, Daniel / Agwuh, Ken / Ail, Dhiraj / Aldera, Erin L. / Alegria, Ana / Allen, Sam / Angus, Brian / Ashish, Abdul / Atkinson, Dougal / Bari, Shahedal / Barlow, Gavin / Barnass, Stella / Barrett, Nicholas / Bassford, Christopher / Basude, Sneha / Baxter, David / Beadsworth, Michael / Bernatoniene, Jolanta / Berridge, John / Berry, Colin / Best, Nicola / Bothma, Pieter / Chadwick, David / Brittain-Long, Robin / Bulteel, Naomi / Burden, Tom / Burtenshaw, Andrew / Caruth, Vikki / Chambler, Duncan / Chee, Nigel / Child, Jenny / Chukkambotla, Srikanth / Clark, Tom / Collini, Paul / Cosgrove, Catherine / Cupitt, Jason / Cutino-Moguel, Maria-Teresa / Dark, Paul / Dawson, Chris / Dervisevic, Samir / Donnison, Phil / Douthwaite, Sam / Drummond, Andrew / DuRand, Ingrid / Dushianthan, Ahilanadan / Dyer, Tristan / Evans, Cariad / Eziefula, Chi / Fegan, Chrisopher / Finn, Adam / Fullerton, Duncan / Garg, Sanjeev / Garg, Atul / Gkrania-Klotsas, Effrossyni / Godden, Jo / Goldsmith, Arthur / Graham, Clive / Hardy, Elaine / Hartshorn, Stuart / Harvey, Daniel / Havalda, Peter / Hawcutt, Daniel B. / Hobrok, Maria / Hodgson, Luke / Hormis, Anil / Jacobs, Michael / Jain, Susan / Jennings, Paul / Kaliappan, Agilan / Kasipandian, Vidya / Kegg, Stephen / Kelsey, Michael / Kendall, Jason / Kerrison, Caroline / Kerslake, Ian / Koch, Oliver / Koduri, Gouri / Kōśi, Jōrjj / Laha, Shondipon / Laird, Steven / Larkin, Susan / Leiner, Tamas / Lillie, Patrick / Limb, James / Linnett, Vanessa / Little, Jeff / Lyttle, Mark / MacMahon, Michael / MacNaughton, Emily / Mankregod, Ravish / Masson, Huw / Matovu, Elijah / McCullough, Katherine / McEwen, Ruth / Meda, Manjula / Mills, Gary / Minton, Jane / Mirfenderesky, Mariyam / Mohandas, Kavya / Mok, Quen / Moon, James / Moore, Elinoor / Morgan, Patrick / Morris, Craig / Mortimore, Katherine / Moses, S. / Mpenge, Mbiye / Mulla, Rohinton / Murphy, Michael / Nagel, Megan / Nagarajan, Thapas / Nelson, Mark / Norris, Lillian / O’Shea, Matthew K. / Otahal, Igor / Ostermann, Marlies / Pais, Mark / Panchatsharam, Selva / Papakonstantinou, Danai / Paraiso, Hassan / Patel, Brij / Pattison, Natalie / Pepperell, Justin / Peters, Mark / Phull, Mandeep / Pintus, Stefania / Pooni, Jagtur Singh / Planche, Tim / Post, Frank / Price, David / Prout, Rachel / Rae, Nikolas / Reschreiter, Henrik / Reynolds, Tim / Richardson, Neil / Roberts, Mark / Roberts, Devender / Rose, Alistair / Rousseau, Guy / Ruge, Bobby / Ryan, Brendan / Saluja, Taranprit / Schmid, Matthias L. / Shah, Aarti / Shanmuga, Prad / Sharma, Anil / Shawcross, Anna / Sizer, Jeremy / Shankar-Hari, Manu / Smith, Richard / Snelson, Catherine / Spittle, Nick / Staines, Nikki / Stambach, Tom / Stewart, Richard / Subudhi, Pradeep / Szakmany, Tamas / Tatham, Kate / Thomas, Jo / Thompson, Chris / Thompson, Robert / Tridente, Ascanio / Tupper-Carey, Darell / Twagira, Mary / Vallotton, Nick / Vancheeswaran, Rama / Vincent-Smith, Lisa / Visuvanathan, Shico / Vuylsteke, Alan / Waddy, Sam / Wake, Rachel / Walden, Andrew / Welters, Ingeborg / Whitehouse, Tony / Whittaker, Paul / Whittington, Ashley / Papineni, Padmasayee / Wijesinghe, Meme / Williams, Martin / Wilson, Lawrence / Winchester, Stephen / Wiselka, Martin / Wolverson, Adam / Wootton, Daniel G. / Workman, Andrew / Yates, Bryan / Young, Peter

    Cell. 2022 Feb. 03, v. 185, no. 3 p.467-484.e15

    2022  

    Abstract: On 24ᵗʰ November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent ... ...

    Institution OPTIC Consortium
    ISARIC4C Consortium
    Abstract On 24ᵗʰ November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses.
    Keywords Severe acute respiratory syndrome coronavirus 2 ; evolution ; neutralization ; pandemic ; vaccines ; SARS-CoV-2 ; Omicron ; variants ; immune evasion ; receptor interaction ; Spike ; RBD
    Language English
    Dates of publication 2022-0203
    Size p. 467-484.e15.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2021.12.046
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

    Nora Franceschini / Claudia Giambartolomei / Paul S. de Vries / Chris Finan / Joshua C. Bis / Rachael P. Huntley / Ruth C. Lovering / Salman M. Tajuddin / Thomas W. Winkler / Misa Graff / Maryam Kavousi / Caroline Dale / Albert V. Smith / Edith Hofer / Elisabeth M. van Leeuwen / Ilja M. Nolte / Lingyi Lu / Markus Scholz / Muralidharan Sargurupremraj /
    Niina Pitkänen / Oscar Franzén / Peter K. Joshi / Raymond Noordam / Riccardo E. Marioni / Shih-Jen Hwang / Solomon K. Musani / Ulf Schminke / Walter Palmas / Aaron Isaacs / Adolfo Correa / Alan B. Zonderman / Albert Hofman / Alexander Teumer / Amanda J. Cox / André G. Uitterlinden / Andrew Wong / Andries J. Smit / Anne B. Newman / Annie Britton / Arno Ruusalepp / Bengt Sennblad / Bo Hedblad / Bogdan Pasaniuc / Brenda W. Penninx / Carl D. Langefeld / Christina L. Wassel / Christophe Tzourio / Cristiano Fava / Damiano Baldassarre / Daniel H. O’Leary / Daniel Teupser / Diana Kuh / Elena Tremoli / Elmo Mannarino / Enzo Grossi / Eric Boerwinkle / Eric E. Schadt / Erik Ingelsson / Fabrizio Veglia / Fernando Rivadeneira / Frank Beutner / Ganesh Chauhan / Gerardo Heiss / Harold Snieder / Harry Campbell / Henry Völzke / Hugh S. Markus / Ian J. Deary / J. Wouter Jukema / Jacqueline de Graaf / Jacqueline Price / Janne Pott / Jemma C. Hopewell / Jingjing Liang / Joachim Thiery / Jorgen Engmann / Karl Gertow / Kenneth Rice / Kent D. Taylor / Klodian Dhana / Lambertus A. L. M. Kiemeney / Lars Lind / Laura M. Raffield / Lenore J. Launer / Lesca M. Holdt / Marcus Dörr / Martin Dichgans / Matthew Traylor / Matthias Sitzer / Meena Kumari / Mika Kivimaki / Mike A. Nalls / Olle Melander / Olli Raitakari / Oscar H. Franco / Oscar L. Rueda-Ochoa / Panos Roussos / Peter H. Whincup / Philippe Amouyel / Philippe Giral / Pramod Anugu / Quenna Wong / Rainer Malik / Rainer Rauramaa / Ralph Burkhardt / Rebecca Hardy / Reinhold Schmidt / Renée de Mutsert / Richard W. Morris / Rona J. Strawbridge / S. Goya Wannamethee / Sara Hägg / Sonia Shah / Stela McLachlan / Stella Trompet / Sudha Seshadri / Sudhir Kurl / Susan R. Heckbert / Susan Ring / Tamara B. Harris / Terho Lehtimäki / Tessel E. Galesloot / Tina Shah / Ulf de Faire / Vincent Plagnol / Wayne D. Rosamond / Wendy Post / Xiaofeng Zhu / Xiaoling Zhang / Xiuqing Guo / Yasaman Saba / MEGASTROKE Consortium / Abbas Dehghan / Adrie Seldenrijk / Alanna C. Morrison / Anders Hamsten / Bruce M. Psaty / Cornelia M. van Duijn / Deborah A. Lawlor / Dennis O. Mook-Kanamori / Donald W. Bowden / Helena Schmidt / James F. Wilson / James G. Wilson / Jerome I. Rotter / Joanna M. Wardlaw / John Deanfield / Julian Halcox / Leo-Pekka Lyytikäinen / Markus Loeffler / Michele K. Evans / Stéphanie Debette / Steve E. Humphries / Uwe Völker / Vilmundur Gudnason / Aroon D. Hingorani / Johan L. M. Björkegren / Juan P. Casas / Christopher J. O’Donnell

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 14

    Abstract: Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and ... ...

    Abstract Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.
    Keywords Science ; Q
    Language English
    Publishing date 2018-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

    Nora Franceschini / Claudia Giambartolomei / Paul S. de Vries / Chris Finan / Joshua C. Bis / Rachael P. Huntley / Ruth C. Lovering / Salman M. Tajuddin / Thomas W. Winkler / Misa Graff / Maryam Kavousi / Caroline Dale / Albert V. Smith / Edith Hofer / Elisabeth M. van Leeuwen / Ilja M. Nolte / Lingyi Lu / Markus Scholz / Muralidharan Sargurupremraj /
    Niina Pitkänen / Oscar Franzén / Peter K. Joshi / Raymond Noordam / Riccardo E. Marioni / Shih-Jen Hwang / Solomon K. Musani / Ulf Schminke / Walter Palmas / Aaron Isaacs / Adolfo Correa / Alan B. Zonderman / Albert Hofman / Alexander Teumer / Amanda J. Cox / André G. Uitterlinden / Andrew Wong / Andries J. Smit / Anne B. Newman / Annie Britton / Arno Ruusalepp / Bengt Sennblad / Bo Hedblad / Bogdan Pasaniuc / Brenda W. Penninx / Carl D. Langefeld / Christina L. Wassel / Christophe Tzourio / Cristiano Fava / Damiano Baldassarre / Daniel H. O’Leary / Daniel Teupser / Diana Kuh / Elena Tremoli / Elmo Mannarino / Enzo Grossi / Eric Boerwinkle / Eric E. Schadt / Erik Ingelsson / Fabrizio Veglia / Fernando Rivadeneira / Frank Beutner / Ganesh Chauhan / Gerardo Heiss / Harold Snieder / Harry Campbell / Henry Völzke / Hugh S. Markus / Ian J. Deary / J. Wouter Jukema / Jacqueline de Graaf / Jacqueline Price / Janne Pott / Jemma C. Hopewell / Jingjing Liang / Joachim Thiery / Jorgen Engmann / Karl Gertow / Kenneth Rice / Kent D. Taylor / Klodian Dhana / Lambertus A. L. M. Kiemeney / Lars Lind / Laura M. Raffield / Lenore J. Launer / Lesca M. Holdt / Marcus Dörr / Martin Dichgans / Matthew Traylor / Matthias Sitzer / Meena Kumari / Mika Kivimaki / Mike A. Nalls / Olle Melander / Olli Raitakari / Oscar H. Franco / Oscar L. Rueda-Ochoa / Panos Roussos / Peter H. Whincup / Philippe Amouyel / Philippe Giral / Pramod Anugu / Quenna Wong / Rainer Malik / Rainer Rauramaa / Ralph Burkhardt / Rebecca Hardy / Reinhold Schmidt / Renée de Mutsert / Richard W. Morris / Rona J. Strawbridge / S. Goya Wannamethee / Sara Hägg / Sonia Shah / Stela McLachlan / Stella Trompet / Sudha Seshadri / Sudhir Kurl / Susan R. Heckbert / Susan Ring / Tamara B. Harris / Terho Lehtimäki / Tessel E. Galesloot / Tina Shah / Ulf de Faire / Vincent Plagnol / Wayne D. Rosamond / Wendy Post / Xiaofeng Zhu / Xiaoling Zhang / Xiuqing Guo / Yasaman Saba / MEGASTROKE Consortium / Abbas Dehghan / Adrie Seldenrijk / Alanna C. Morrison / Anders Hamsten / Bruce M. Psaty / Cornelia M. van Duijn / Deborah A. Lawlor / Dennis O. Mook-Kanamori / Donald W. Bowden / Helena Schmidt / James F. Wilson / James G. Wilson / Jerome I. Rotter / Joanna M. Wardlaw / John Deanfield / Julian Halcox / Leo-Pekka Lyytikäinen / Markus Loeffler / Michele K. Evans / Stéphanie Debette / Steve E. Humphries / Uwe Völker / Vilmundur Gudnason / Aroon D. Hingorani / Johan L. M. Björkegren / Juan P. Casas / Christopher J. O’Donnell

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 14

    Abstract: Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and ... ...

    Abstract Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.
    Keywords Science ; Q
    Language English
    Publishing date 2018-12-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.

    Franceschini, Nora / Giambartolomei, Claudia / de Vries, Paul S / Finan, Chris / Bis, Joshua C / Huntley, Rachael P / Lovering, Ruth C / Tajuddin, Salman M / Winkler, Thomas W / Graff, Misa / Kavousi, Maryam / Dale, Caroline / Smith, Albert V / Hofer, Edith / van Leeuwen, Elisabeth M / Nolte, Ilja M / Lu, Lingyi / Scholz, Markus / Sargurupremraj, Muralidharan /
    Pitkänen, Niina / Franzén, Oscar / Joshi, Peter K / Noordam, Raymond / Marioni, Riccardo E / Hwang, Shih-Jen / Musani, Solomon K / Schminke, Ulf / Palmas, Walter / Isaacs, Aaron / Correa, Adolfo / Zonderman, Alan B / Hofman, Albert / Teumer, Alexander / Cox, Amanda J / Uitterlinden, André G / Wong, Andrew / Smit, Andries J / Newman, Anne B / Britton, Annie / Ruusalepp, Arno / Sennblad, Bengt / Hedblad, Bo / Pasaniuc, Bogdan / Penninx, Brenda W / Langefeld, Carl D / Wassel, Christina L / Tzourio, Christophe / Fava, Cristiano / Baldassarre, Damiano / O'Leary, Daniel H / Teupser, Daniel / Kuh, Diana / Tremoli, Elena / Mannarino, Elmo / Grossi, Enzo / Boerwinkle, Eric / Schadt, Eric E / Ingelsson, Erik / Veglia, Fabrizio / Rivadeneira, Fernando / Beutner, Frank / Chauhan, Ganesh / Heiss, Gerardo / Snieder, Harold / Campbell, Harry / Völzke, Henry / Markus, Hugh S / Deary, Ian J / Jukema, J Wouter / de Graaf, Jacqueline / Price, Jacqueline / Pott, Janne / Hopewell, Jemma C / Liang, Jingjing / Thiery, Joachim / Engmann, Jorgen / Gertow, Karl / Rice, Kenneth / Taylor, Kent D / Dhana, Klodian / Kiemeney, Lambertus A L M / Lind, Lars / Raffield, Laura M / Launer, Lenore J / Holdt, Lesca M / Dörr, Marcus / Dichgans, Martin / Traylor, Matthew / Sitzer, Matthias / Kumari, Meena / Kivimaki, Mika / Nalls, Mike A / Melander, Olle / Raitakari, Olli / Franco, Oscar H / Rueda-Ochoa, Oscar L / Roussos, Panos / Whincup, Peter H / Amouyel, Philippe / Giral, Philippe / Anugu, Pramod / Wong, Quenna / Malik, Rainer / Rauramaa, Rainer / Burkhardt, Ralph / Hardy, Rebecca / Schmidt, Reinhold / de Mutsert, Renée / Morris, Richard W / Strawbridge, Rona J / Wannamethee, S Goya / Hägg, Sara / Shah, Sonia / McLachlan, Stela / Trompet, Stella / Seshadri, Sudha / Kurl, Sudhir / Heckbert, Susan R / Ring, Susan / Harris, Tamara B / Lehtimäki, Terho / Galesloot, Tessel E / Shah, Tina / de Faire, Ulf / Plagnol, Vincent / Rosamond, Wayne D / Post, Wendy / Zhu, Xiaofeng / Zhang, Xiaoling / Guo, Xiuqing / Saba, Yasaman / Dehghan, Abbas / Seldenrijk, Adrie / Morrison, Alanna C / Hamsten, Anders / Psaty, Bruce M / van Duijn, Cornelia M / Lawlor, Deborah A / Mook-Kanamori, Dennis O / Bowden, Donald W / Schmidt, Helena / Wilson, James F / Wilson, James G / Rotter, Jerome I / Wardlaw, Joanna M / Deanfield, John / Halcox, Julian / Lyytikäinen, Leo-Pekka / Loeffler, Markus / Evans, Michele K / Debette, Stéphanie / Humphries, Steve E / Völker, Uwe / Gudnason, Vilmundur / Hingorani, Aroon D / Björkegren, Johan L M / Casas, Juan P / O'Donnell, Christopher J

    Nature communications

    2018  Volume 9, Issue 1, Page(s) 5141

    Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71, ...

    Abstract Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
    MeSH term(s) ADAMTS9 Protein/genetics ; Amino Acid Oxidoreductases/genetics ; Carotid Intima-Media Thickness ; Coronary Disease/genetics ; Coronary Disease/pathology ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study/methods ; Humans ; Lod Score ; Plaque, Atherosclerotic/genetics ; Plaque, Atherosclerotic/pathology ; Polymorphism, Single Nucleotide ; Protein-Lysine 6-Oxidase ; Quantitative Trait Loci/genetics ; Risk Factors
    Chemical Substances Amino Acid Oxidoreductases (EC 1.4.-) ; LOXL4 protein, human (EC 1.4.3.-) ; Protein-Lysine 6-Oxidase (EC 1.4.3.13) ; ADAMTS9 Protein (EC 3.4.24.-) ; ADAMTS9 protein, human (EC 3.4.24.-)
    Language English
    Publishing date 2018-12-03
    Publishing country England
    Document type Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-018-07340-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

    Sampson, Joshua N / Wheeler, William A / Yeager, Meredith / Panagiotou, Orestis / Wang, Zhaoming / Berndt, Sonja I / Lan, Qing / Abnet, Christian C / Amundadottir, Laufey T / Figueroa, Jonine D / Landi, Maria Teresa / Mirabello, Lisa / Savage, Sharon A / Taylor, Philip R / De Vivo, Immaculata / McGlynn, Katherine A / Purdue, Mark P / Rajaraman, Preetha / Adami, Hans-Olov /
    Ahlbom, Anders / Albanes, Demetrius / Amary, Maria Fernanda / An, She-Juan / Andersson, Ulrika / Andriole, Gerald / Andrulis, Irene L / Angelucci, Emanuele / Ansell, Stephen M / Arici, Cecilia / Armstrong, Bruce K / Arslan, Alan A / Austin, Melissa A / Baris, Dalsu / Barkauskas, Donald A / Bassig, Bryan A / Becker, Nikolaus / Benavente, Yolanda / Benhamou, Simone / Berg, Christine / Van Den Berg, David / Bernstein, Leslie / Bertrand, Kimberly A / Birmann, Brenda M / Black, Amanda / Boeing, Heiner / Boffetta, Paolo / Boutron-Ruault, Marie-Christine / Bracci, Paige M / Brinton, Louise / Brooks-Wilson, Angela R / Bueno-de-Mesquita, H Bas / Burdett, Laurie / Buring, Julie / Butler, Mary Ann / Cai, Qiuyin / Cancel-Tassin, Geraldine / Canzian, Federico / Carrato, Alfredo / Carreon, Tania / Carta, Angela / Chan, John K C / Chang, Ellen T / Chang, Gee-Chen / Chang, I-Shou / Chang, Jiang / Chang-Claude, Jenny / Chen, Chien-Jen / Chen, Chih-Yi / Chen, Chu / Chen, Chung-Hsing / Chen, Constance / Chen, Hongyan / Chen, Kexin / Chen, Kuan-Yu / Chen, Kun-Chieh / Chen, Ying / Chen, Ying-Hsiang / Chen, Yi-Song / Chen, Yuh-Min / Chien, Li-Hsin / Chirlaque, María-Dolores / Choi, Jin Eun / Choi, Yi Young / Chow, Wong-Ho / Chung, Charles C / Clavel, Jacqueline / Clavel-Chapelon, Françoise / Cocco, Pierluigi / Colt, Joanne S / Comperat, Eva / Conde, Lucia / Connors, Joseph M / Conti, David / Cortessis, Victoria K / Cotterchio, Michelle / Cozen, Wendy / Crouch, Simon / Crous-Bou, Marta / Cussenot, Olivier / Davis, Faith G / Ding, Ti / Diver, W Ryan / Dorronsoro, Miren / Dossus, Laure / Duell, Eric J / Ennas, Maria Grazia / Erickson, Ralph L / Feychting, Maria / Flanagan, Adrienne M / Foretova, Lenka / Fraumeni, Joseph F / Freedman, Neal D / Beane Freeman, Laura E / Fuchs, Charles / Gago-Dominguez, Manuela / Gallinger, Steven / Gao, Yu-Tang / Gapstur, Susan M / Garcia-Closas, Montserrat / García-Closas, Reina / Gascoyne, Randy D / Gastier-Foster, Julie / Gaudet, Mia M / Gaziano, J Michael / Giffen, Carol / Giles, Graham G / Giovannucci, Edward / Glimelius, Bengt / Goggins, Michael / Gokgoz, Nalan / Goldstein, Alisa M / Gorlick, Richard / Gross, Myron / Grubb, Robert / Gu, Jian / Guan, Peng / Gunter, Marc / Guo, Huan / Habermann, Thomas M / Haiman, Christopher A / Halai, Dina / Hallmans, Goran / Hassan, Manal / Hattinger, Claudia / He, Qincheng / He, Xingzhou / Helzlsouer, Kathy / Henderson, Brian / Henriksson, Roger / Hjalgrim, Henrik / Hoffman-Bolton, Judith / Hohensee, Chancellor / Holford, Theodore R / Holly, Elizabeth A / Hong, Yun-Chul / Hoover, Robert N / Horn-Ross, Pamela L / Hosain, G M Monawar / Hosgood, H Dean / Hsiao, Chin-Fu / Hu, Nan / Hu, Wei / Hu, Zhibin / Huang, Ming-Shyan / Huerta, Jose-Maria / Hung, Jen-Yu / Hutchinson, Amy / Inskip, Peter D / Jackson, Rebecca D / Jacobs, Eric J / Jenab, Mazda / Jeon, Hyo-Sung / Ji, Bu-Tian / Jin, Guangfu / Jin, Li / Johansen, Christoffer / Johnson, Alison / Jung, Yoo Jin / Kaaks, Rudolph / Kamineni, Aruna / Kane, Eleanor / Kang, Chang Hyun / Karagas, Margaret R / Kelly, Rachel S / Khaw, Kay-Tee / Kim, Christopher / Kim, Hee Nam / Kim, Jin Hee / Kim, Jun Suk / Kim, Yeul Hong / Kim, Young Tae / Kim, Young-Chul / Kitahara, Cari M / Klein, Alison P / Klein, Robert J / Kogevinas, Manolis / Kohno, Takashi / Kolonel, Laurence N / Kooperberg, Charles / Kricker, Anne / Krogh, Vittorio / Kunitoh, Hideo / Kurtz, Robert C / Kweon, Sun-Seog / LaCroix, Andrea / Lawrence, Charles / Lecanda, Fernando / Lee, Victor Ho Fun / Li, Donghui / Li, Haixin / Li, Jihua / Li, Yao-Jen / Li, Yuqing / Liao, Linda M / Liebow, Mark / Lightfoot, Tracy / Lim, Wei-Yen / Lin, Chien-Chung / Lin, Dongxin / Lindstrom, Sara / Linet, Martha S / Link, Brian K / Liu, Chenwei / Liu, Jianjun / Liu, Li / Ljungberg, Börje / Lloreta, Josep / Di Lollo, Simonetta / Lu, Daru / Lund, Eiluv / Malats, Nuria / Mannisto, Satu / Le Marchand, Loic / Marina, Neyssa / Masala, Giovanna / Mastrangelo, Giuseppe / Matsuo, Keitaro / Maynadie, Marc / McKay, James / McKean-Cowdin, Roberta / Melbye, Mads / Melin, Beatrice S / Michaud, Dominique S / Mitsudomi, Tetsuya / Monnereau, Alain / Montalvan, Rebecca / Moore, Lee E / Mortensen, Lotte Maxild / Nieters, Alexandra / North, Kari E / Novak, Anne J / Oberg, Ann L / Offit, Kenneth / Oh, In-Jae / Olson, Sara H / Palli, Domenico / Pao, William / Park, In Kyu / Park, Jae Yong / Park, Kyong Hwa / Patiño-Garcia, Ana / Pavanello, Sofia / Peeters, Petra H M / Perng, Reury-Perng / Peters, Ulrike / Petersen, Gloria M / Picci, Piero / Pike, Malcolm C / Porru, Stefano / Prescott, Jennifer / Prokunina-Olsson, Ludmila / Qian, Biyun / Qiao, You-Lin / Rais, Marco / Riboli, Elio / Riby, Jacques / Risch, Harvey A / Rizzato, Cosmeri / Rodabough, Rebecca / Roman, Eve / Roupret, Morgan / Ruder, Avima M / Sanjose, Silvia de / Scelo, Ghislaine / Schned, Alan / Schumacher, Fredrick / Schwartz, Kendra / Schwenn, Molly / Scotlandi, Katia / Seow, Adeline / Serra, Consol / Serra, Massimo / Sesso, Howard D / Setiawan, Veronica Wendy / Severi, Gianluca / Severson, Richard K / Shanafelt, Tait D / Shen, Hongbing / Shen, Wei / Shin, Min-Ho / Shiraishi, Kouya / Shu, Xiao-Ou / Siddiq, Afshan / Sierrasesúmaga, Luis / Sihoe, Alan Dart Loon / Skibola, Christine F / Smith, Alex / Smith, Martyn T / Southey, Melissa C / Spinelli, John J / Staines, Anthony / Stampfer, Meir / Stern, Marianna C / Stevens, Victoria L / Stolzenberg-Solomon, Rachael S / Su, Jian / Su, Wu-Chou / Sund, Malin / Sung, Jae Sook / Sung, Sook Whan / Tan, Wen / Tang, Wei / Tardón, Adonina / Thomas, David / Thompson, Carrie A / Tinker, Lesley F / Tirabosco, Roberto / Tjønneland, Anne / Travis, Ruth C / Trichopoulos, Dimitrios / Tsai, Fang-Yu / Tsai, Ying-Huang / Tucker, Margaret / Turner, Jenny / Vajdic, Claire M / Vermeulen, Roel C H / Villano, Danylo J / Vineis, Paolo / Virtamo, Jarmo / Visvanathan, Kala / Wactawski-Wende, Jean / Wang, Chaoyu / Wang, Chih-Liang / Wang, Jiu-Cun / Wang, Junwen / Wei, Fusheng / Weiderpass, Elisabete / Weiner, George J / Weinstein, Stephanie / Wentzensen, Nicolas / White, Emily / Witzig, Thomas E / Wolpin, Brian M / Wong, Maria Pik / Wu, Chen / Wu, Guoping / Wu, Junjie / Wu, Tangchun / Wu, Wei / Wu, Xifeng / Wu, Yi-Long / Wunder, Jay S / Xiang, Yong-Bing / Xu, Jun / Xu, Ping / Yang, Pan-Chyr / Yang, Tsung-Ying / Ye, Yuanqing / Yin, Zhihua / Yokota, Jun / Yoon, Ho-Il / Yu, Chong-Jen / Yu, Herbert / Yu, Kai / Yuan, Jian-Min / Zelenetz, Andrew / Zeleniuch-Jacquotte, Anne / Zhang, Xu-Chao / Zhang, Yawei / Zhao, Xueying / Zhao, Zhenhong / Zheng, Hong / Zheng, Tongzhang / Zheng, Wei / Zhou, Baosen / Zhu, Meng / Zucca, Mariagrazia / Boca, Simina M / Cerhan, James R / Ferri, Giovanni M / Hartge, Patricia / Hsiung, Chao Agnes / Magnani, Corrado / Miligi, Lucia / Morton, Lindsay M / Smedby, Karin E / Teras, Lauren R / Vijai, Joseph / Wang, Sophia S / Brennan, Paul / Caporaso, Neil E / Hunter, David J / Kraft, Peter / Rothman, Nathaniel / Silverman, Debra T / Slager, Susan L / Chanock, Stephen J / Chatterjee, Nilanjan

    Journal of the National Cancer Institute

    2015  Volume 107, Issue 12, Page(s) djv279

    Abstract: Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms ( ...

    Abstract Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.
    Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.
    Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.
    Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
    MeSH term(s) Adult ; Aged ; Asian People/genetics ; Asian People/statistics & numerical data ; Bone Neoplasms/genetics ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Kidney Neoplasms/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Lung Neoplasms/etiology ; Lung Neoplasms/genetics ; Lymphoma, Large B-Cell, Diffuse/genetics ; Male ; Middle Aged ; Neoplasms/etiology ; Neoplasms/genetics ; Osteosarcoma/genetics ; Polymorphism, Single Nucleotide ; Smoking/adverse effects ; Testicular Neoplasms/genetics ; Tissue Array Analysis ; Urinary Bladder Neoplasms/etiology ; Urinary Bladder Neoplasms/genetics ; White People/genetics ; White People/statistics & numerical data
    Language English
    Publishing date 2015-10-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2992-0
    ISSN 1460-2105 ; 0027-8874 ; 0198-0157
    ISSN (online) 1460-2105
    ISSN 0027-8874 ; 0198-0157
    DOI 10.1093/jnci/djv279
    Database MEDical Literature Analysis and Retrieval System OnLINE

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