Second-generation PLINK: rising to the challenge of larger and richer datasets
Christopher C. Chang,Carson C. Chow,Laurent C. A. M. Tellier,Shashaank Vattikuti,Shaun Purcell,James J. Lee +5 more
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TLDR
PLINK as discussed by the authors is a C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics, which has been widely used in the literature.Abstract:
PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format.
To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information.
The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.read more
Citations
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Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system.
Julia Ramirez,Stefan van Duijvenboden,Stefan van Duijvenboden,Ioanna Ntalla,Borbala Mifsud,Helen R. Warren,Evan Tzanis,Michele Orini,Andrew Tinker,Pier D. Lambiase,Patricia B. Munroe +10 more
TL;DR: The authors examine both traits in a two-stage GWAS design in up to 67,257 individuals from UK Biobank to reinforce current understanding of HR response to exercise and recovery and could guide future studies evaluating its contribution to cardiovascular risk prediction.
Posted ContentDOI
Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors
Niamh Mullins,Jooeun Kang,Adrian I. Campos,Adrian I. Campos,Jonathan R. I. Coleman,Jonathan R. I. Coleman,Alexis C. Edwards,Hanga Galfalvy,Daniel F. Levey,Daniel F. Levey,Adriana Lori,Andrey A. Shabalin,Anna Starnawska,Mei-Hsin Su,Hunna J. Watson,Hunna J. Watson,Hunna J. Watson,Mark Adams,Swapnil Awasthi,Michael J. Gandal,Jonathan D. Hafferty,Akitoyo Hishimoto,Minsoo Kim,Satoshi Okazaki,Ikuo Otsuka,Ikuo Otsuka,Stephan Ripke,Stephan Ripke,Stephan Ripke,Erin B. Ware,Andrew W. Bergen,Wade H. Berrettini,Martin Bohus,Harry Brandt,Xiao Chang,Wei J. Chen,Wei J. Chen,Hsi-Chung Chen,Steven Crawford,Scott J. Crow,Emily DiBlasi,Philibert Duriez,Fernando Fernández-Aranda,Manfred M. Fichter,Steven Gallinger,Stephen J. Glatt,Philip Gorwood,Yiran Guo,Hakon Hakonarson,Hakon Hakonarson,Katherine A. Halmi,Hai-Gwo Hwu,Sonia Jain,Stéphane Jamain,Susana Jiménez-Murcia,Craig Johnson,Allan S. Kaplan,Allan S. Kaplan,Walter H. Kaye,Pamela K. Keel,James L. Kennedy,James L. Kennedy,Kelly L. Klump,Robert D. Levitan,Robert D. Levitan,Dong Li,Shih-Cheng Liao,Klaus Lieb,Lisa Lilenfeld,Chih-Min Liu,Pierre J. Magistretti,Pierre J. Magistretti,Christian R. Marshall,James E. Mitchell,Eric T. Monson,Richard M. Myers,Dalila Pinto,Abigail Powers,Nicolas Ramoz,Stefan Roepke,Alessandro Rotondo,Vsevolod Rozanov,Stephen W. Scherer,Christian Schmahl,M. Sokolowski,Michael Strober,Michael Strober,Laura M. Thornton,Janet Treasure,Janet Treasure,Ming T. Tsuang,Maria La Via,Stephanie H. Witt,D. Blake Woodside,Zeynep Yilmaz,Zeynep Yilmaz,Lea Zillich,Rolf Adolfsson,Ingrid Agartz,Ingrid Agartz,Tracy Air,Martin Alda,Lars Alfredsson,Ole A. Andreassen,Ole A. Andreassen,Adebayo Anjorin,Vivek Appadurai,Vivek Appadurai,María Soler Artigas,Sandra Van der Auwera,M. Helena Azevedo,Nicholas Bass,Claiton Hd Bau,Bernhard T. Baune,Bernhard T. Baune,Frank Bellivier,Klaus Berger,Joanna M. Biernacka,Tim B. Bigdeli,Tim B. Bigdeli,Elisabeth B. Binder,Elisabeth B. Binder,Michael Boehnke,Marco P. Boks,Rosa Bosch,Rosa Bosch,David L. Braff,Richard A. Bryant,Monika Budde,Enda M. Byrne,Wiepke Cahn,Miguel Casas,Enrique Castelao,Jorge A. Cervilla,Boris Chaumette,Boris Chaumette,Sven Cichon,Aiden Corvin,Nicholas John Craddock,David Craig,Franziska Degenhardt,Srdjan Djurovic,Srdjan Djurovic,Howard J. Edenberg,Ayman H. Fanous,Ayman H. Fanous,Jerome C. Foo,Andreas J. Forstner,Andreas J. Forstner,Andreas J. Forstner,Mark A. Frye,Janice M. Fullerton,Janice M. Fullerton,Justine M. Gatt,Pablo V. Gejman,Pablo V. Gejman,Ina Giegling,Ina Giegling,Hans J. Grabe,Melissa J. Green,Melissa J. Green,Eugenio H. Grevet,Maria Grigoroiu-Serbanescu,Blanca Gutiérrez,Jose Guzman-Parra,Steven P. Hamilton,Marian L. Hamshere,Annette M. Hartmann,Joanna Hauser,Stefanie Heilmann-Heimbach,Per Hoffmann,Per Hoffmann,Per Hoffmann,Marcus Ising,Ian Jones,Lisa Jones,Lina Jonsson,René S. Kahn,John R. Kelsoe,Kenneth S. Kendler,Stefan Kloiber,Stefan Kloiber,Stefan Kloiber,Karestan C. Koenen,Karestan C. Koenen,Manolis Kogevinas,Bettina Konte,Marie-Odile Krebs,Marie-Odile Krebs,Mikael Landén,Mikael Landén,Jacob Lawrence,Marion Leboyer,Marion Leboyer,Phil Lee,Phil Lee,Douglas F. Levinson,Calwing Liao,Calwing Liao,Jolanta Lissowska,Susanne Lucae,Fermín Mayoral,Susan L. McElroy,Patrick J. McGrath,Peter McGuffin,Andrew McQuillin,Sarah E. Medland,Divya Mehta,Divya Mehta,Ingrid Melle,Ingrid Melle,Yuri Milaneschi,Philip B. Mitchell,Esther Molina,Gunnar Morken,Preben Bo Mortensen,Bertram Müller-Myhsok,Bertram Müller-Myhsok,Caroline M. Nievergelt,Vishwajit L. Nimgaonkar,Markus M. Nöthen,Michael Conlon O'Donovan,Roel A. Ophoff,Roel A. Ophoff,Michael John Owen,Carlos N. Pato,Michele T. Pato,Brenda W.J.H. Penninx,Jonathan Pimm,Giorgio Pistis,James B. Potash,Robert A Power,Robert A Power,Martin Preisig,Digby Quested,Josep Antoni Ramos-Quiroga,Andreas Reif,Marta Ribasés,Vanesa Richarte,Vanesa Richarte,Marcella Rietschel,Margarita Rivera,Margarita Rivera,Andrea L. Roberts,Gloria Roberts,Guy A. Rouleau,Guy A. Rouleau,Diego L. Rovaris,Dan Rujescu,Cristina Sánchez-Mora,Alan R. Sanders,Alan R. Sanders,Peter R. Schofield,Peter R. Schofield,Thomas G. Schulze,Laura J. Scott,Alessandro Serretti,Jianxin Shi,Stanley I. Shyn,Lea Sirignano,Pamela Sklar,Olav B. Smeland,Olav B. Smeland,Jordan W. Smoller,Jordan W. Smoller,Edmund J.S. Sonuga-Barke,Gianfranco Spalletta,John Strauss,John Strauss,Beata Świątkowska,Maciej Trzaskowski,Gustavo Turecki,Laura Vilar-Ribó,John B. Vincent,Henry Völzke,James T.R. Walters,Cynthia Shannon Weickert,Thomas W. Weickert,Myrna M. Weissman,Leanne M. Williams,Naomi R. Wray,Clement C. Zai,Esben Agerbo,Esben Agerbo,Anders D. Børglum,Gerome Breen,Gerome Breen,Annette Erlangsen,Tõnu Esko,Tõnu Esko,Joel Gelernter,Joel Gelernter,David M. Hougaard,David M. Hougaard,Ronald C. Kessler,Henry R. Kranzler,Qingqin S. Li,Nicholas G. Martin,Andrew M. McIntosh,Sarah E. Medland,Ole Mors,Ole Mors,Merete Nordentoft,Merete Nordentoft,Catherine M. Olsen,David J. Porteous,Robert J. Ursano,Danuta Wasserman,Thomas Werge,David C. Whiteman,Cynthia M. Bulik,Cynthia M. Bulik,Hilary Coon,Ditte Demontis,Anna R. Docherty,Anna R. Docherty,Po-Hsiu Kuo,Cathryn M. Lewis,J. John Mann,Miguel E. Rentería,Miguel E. Rentería,Daniel J. Smith,Eli A. Stahl,Eli A. Stahl,Murray B. Stein,Fabian Streit,Virginia L. Willour,Douglas M. Ruderfer +327 more
TL;DR: The results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest the existence of a shared genetic etiology between SA and known risk factors that is not mediated by psychiatric disorders.
Journal ArticleDOI
Genome-wide analysis of insomnia disorder.
Murray B. Stein,Murray B. Stein,Michael McCarthy,Michael McCarthy,Chia-Yen Chen,Chia-Yen Chen,Sonia Jain,Joel Gelernter,Feng He,Steven G. Heeringa,Ronald C. Kessler,Matthew K. Nock,Stephan Ripke,Xiaoying Sun,Gary H. Wynn,Jordan W. Smoller,Jordan W. Smoller,Robert J. Ursano +17 more
TL;DR: Genetic contributions to insomnia disorder in STARRS were significantly positively correlated with major depressive disorder, and subjective well being, and negatively with morningness chronotype in external datasets.
Journal ArticleDOI
Interferon inducible X-linked gene CXorf21 may contribute to sexual dimorphism in Systemic Lupus Erythematosus
Christopher A. Odhams,Christopher A. Odhams,Amy L. Roberts,Susan K. Vester,Carolina S. T. Duarte,Charlie T. Beales,Alexander J. Clarke,Sonja Lindinger,Sonja Lindinger,Samuel J. Daffern,Samuel J. Daffern,Antonino Zito,Lingyan Chen,Lingyan Chen,Leonardo Jones,Lora Boteva,Lora Boteva,David L. Morris,Kerrin S. Small,Michelle M. A. Fernando,Deborah S. Cunninghame Graham,Timothy J. Vyse +21 more
TL;DR: Modulation in gene expression affected by the combination of two hallmarks of SLE is revealed: CXorf21 expression increases in a both an IFN-inducible and sex-specific manner.
Journal ArticleDOI
Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank.
Emmi Tikkanen,Stefan Gustafsson,David Amar,Anna Shcherbina,Daryl Waggott,Euan A. Ashley,Erik Ingelsson,Erik Ingelsson +7 more
TL;DR: The results show shared genetic aetiology between grip strength, and cardiometabolic and cognitive health; and suggest that maintaining muscular strength could prevent future cardiovascular events.
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A reference panel of 64,976 haplotypes for genotype imputation
Shane A. McCarthy,Sayantan Das,Warren W. Kretzschmar,Olivier Delaneau,Andrew R. Wood,Alexander Teumer,Hyun Min Kang,Christian Fuchsberger,Petr Danecek,Kevin Sharp,Yang Luo,C Sidore,Alan Kwong,Nicholas J. Timpson,Seppo Koskinen,Scott I. Vrieze,Laura J. Scott,He Zhang,Anubha Mahajan,Jan H. Veldink,Ulrike Peters,Ulrike Peters,Carlos N. Pato,Cornelia M. van Duijn,Christopher E. Gillies,Ilaria Gandin,Massimo Mezzavilla,Arthur Gilly,Massimiliano Cocca,Michela Traglia,Andrea Angius,Jeffrey C. Barrett,D.I. Boomsma,Kari Branham,Gerome Breen,Gerome Breen,Chad M. Brummett,Fabio Busonero,Harry Campbell,Andrew T. Chan,Sai Chen,Emily Y. Chew,Francis S. Collins,Laura J Corbin,George Davey Smith,George Dedoussis,Marcus Dörr,Aliki-Eleni Farmaki,Luigi Ferrucci,Lukas Forer,Ross M. Fraser,Stacey Gabriel,Shawn Levy,Leif Groop,Leif Groop,Tabitha A. Harrison,Andrew T. Hattersley,Oddgeir L. Holmen,Kristian Hveem,Matthias Kretzler,James Lee,Matt McGue,Thomas Meitinger,David Melzer,Josine L. Min,Karen L. Mohlke,John B. Vincent,Matthias Nauck,Deborah A. Nickerson,Aarno Palotie,Aarno Palotie,Michele T. Pato,Nicola Pirastu,Melvin G. McInnis,J. Brent Richards,J. Brent Richards,Cinzia Sala,Veikko Salomaa,David Schlessinger,Sebastian Schoenherr,P. Eline Slagboom,Kerrin S. Small,Tim D. Spector,Dwight Stambolian,Marcus A. Tuke,Jaakko Tuomilehto,Leonard H. van den Berg,Wouter van Rheenen,Uwe Völker,Cisca Wijmenga,Daniela Toniolo,Eleftheria Zeggini,Paolo Gasparini,Matthew G. Sampson,James F. Wilson,Timothy M. Frayling,Paul I.W. de Bakker,Morris A. Swertz,Steven A. McCarroll,Charles Kooperberg,Annelot M. Dekker,David Altshuler,Cristen J. Willer,William G. Iacono,Samuli Ripatti,Nicole Soranzo,Nicole Soranzo,Klaudia Walter,Anand Swaroop,Francesco Cucca,Carl A. Anderson,Richard M. Myers,Michael Boehnke,Mark I. McCarthy,Mark I. McCarthy,Richard Durbin,Gonçalo R. Abecasis,Jonathan Marchini +117 more