Advancing human genetics research and drug discovery through exome sequencing of the UK Biobank.
Joseph D. Szustakowski,Suganthi Balasubramanian,Erika Kvikstad,Shareef Khalid,Paola G. Bronson,Ariella Sasson,Emily Wong,Daren Liu,J. Wade Davis,Carolina Haefliger,A. Katrina Loomis,Rajesh Mikkilineni,Hyun Ji Noh,Samir Wadhawan,Xiaodong Bai,Alicia Hawes,Olga Krasheninina,Ricardo Ulloa,Alex Lopez,E. N. Smith,Jeffrey F. Waring,Christopher D. Whelan,Ellen A. Tsai,John D. Overton,William J. Salerno,Howard J. Jacob,Sándor Szalma,Heiko Runz,Gregory Hinkle,Paul Nioi,Slavé Petrovski,Melissa R. Miller,Aris Baras,Lyndon J. Mitnaul,Jeffrey G. Reid +34 more
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TLDR
The UK Biobank Exome Sequencing Consortium (UKB-ESC) as mentioned in this paper is a private-public partnership between the UK Biopartition and eight biopharmaceutical companies that will complete the sequencing of exomes for all ~500,000 UKB participants.Abstract:
The UK Biobank Exome Sequencing Consortium (UKB-ESC) is a private–public partnership between the UK Biobank (UKB) and eight biopharmaceutical companies that will complete the sequencing of exomes for all ~500,000 UKB participants. Here, we describe the early results from ~200,000 UKB participants and the features of this project that enabled its success. The biopharmaceutical industry has increasingly used human genetics to improve success in drug discovery. Recognizing the need for large-scale human genetics data, as well as the unique value of the data access and contribution terms of the UKB, the UKB-ESC was formed. As a result, exome data from 200,643 UKB enrollees are now available. These data include ~10 million exonic variants—a rich resource of rare coding variation that is particularly valuable for drug discovery. The UKB-ESC precompetitive collaboration has further strengthened academic and industry ties and has provided teams with an opportunity to interact with and learn from the wider research community. The UK Biobank Exome Sequencing Consortium aims to sequence all the exomes of approximately 500,000 UK Biobank participants. This Perspective describes the results from approximately 200,000 exomes and discusses the lessons learned from this UK Biobank–biopharmaceutical company collaboration.read more
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Exome sequencing and analysis of 454,787 UK Biobank participants.
Joshua D. Backman,Alexander H. Li,Anthony Marcketta,Dylan Sun,Joelle Mbatchou,Michael D. Kessler,Christian Benner,Daren Liu,Adam E. Locke,Suganthi Balasubramanian,Ashish Yadav,Nilanjana Banerjee,Christopher E. Gillies,Amy Damask,Simon Liu,Xiaodong Bai,Alicia Hawes,Evan Maxwell,Lauren Gurski,Kyoko Watanabe,Jack A. Kosmicki,Veera M. Rajagopal,Jason Mighty,Marcus B. Jones,Lyndon J. Mitnaul,Eli A. Stahl,Giovanni Coppola,Eric Jorgenson,Lukas Habegger,William J Salerno,Alan R. Shuldiner,Luca A. Lotta,John D. Overton,Michael N. Cantor,Jeffrey G. Reid,George D. Yancopoulos,Hyun Min Kang,Jonathan Marchini,Aris Baras,Gonçalo R. Abecasis,Manuel A. R. Ferreira +40 more
TL;DR: This paper used exome sequencing to explore protein altering variants and their consequences in 454,787 UK Biobank study participants and identified 12 million coding variants, including ~1 million loss-of-function and ~1.8 million deleterious missense variants.
Journal ArticleDOI
Rare variant contribution to human disease in 281,104 UK Biobank exomes.
Quanli Wang,Ryan S. Dhindsa,Keren J Carss,Andrew R. Harper,Abhishek Nag,Ioanna Tachmazidou,Dimitrios Vitsios,Sri V V Deevi,A. Mackay,Daniel Muthas,Michael Huhn,Susan J. Monkley,Henric Olsson,Sebastian Wasilewski,Katherine R. Smith,Ruth March,Adam Platt,Carolina Haefliger,Slavé Petrovski,Slavé Petrovski +19 more
TL;DR: This paper studied the relationship between rare protein-coding variants and 17,361 binary and 1,419 quantitative phenotypes using exome sequencing data from 269,171 UK Biobank participants of European ancestry.
Journal ArticleDOI
Genetic insights into biological mechanisms governing human ovarian ageing.
Katherine S. Ruth,Felix R. Day,Jazib Hussain,Ana Martínez-Marchal,Catherine E. Aiken,Ajuna Azad,Deborah J. Thompson,Lucie Knoblochova,Lucie Knoblochova,Hironori Abe,Jane L. Tarry-Adkins,Javier Martin Gonzalez,Pierre Fontanillas,Annique Claringbould,Olivier B. Bakker,Patrick Sulem,Robin G. Walters,Chikashi Terao,Sandra Turon,Momoko Horikoshi,Kuang Lin,N. Charlotte Onland-Moret,Aditya Sankar,Emil Peter Thrane Hertz,Pascal Timshel,Vallari Shukla,Rehannah Borup,Kristina W. Olsen,Kristina W. Olsen,Paula Aguilera,Paula Aguilera,Mònica Ferrer-Roda,Yan Huang,Stasa Stankovic,Paul R. H. J. Timmers,Paul R. H. J. Timmers,Thomas U. Ahearn,Behrooz Z. Alizadeh,Elnaz Naderi,Irene L. Andrulis,Irene L. Andrulis,Alice M. Arnold,Kristan J. Aronson,Annelie Augustinsson,Stefania Bandinelli,Caterina Barbieri,Robin N Beaumont,Heiko Becher,Matthias W. Beckmann,Stefania Benonisdottir,Sven Bergmann,Sven Bergmann,Murielle Bochud,Eric Boerwinkle,Stig E. Bojesen,Stig E. Bojesen,Manjeet K. Bolla,Dorret I. Boomsma,Dorret I. Boomsma,Nicholas Bowker,Jennifer A. Brody,Linda Broer,Julie E. Buring,Julie E. Buring,Archie Campbell,Harry Campbell,Jose E. Castelao,Eulalia Catamo,Stephen J. Chanock,Georgia Chenevix-Trench,Marina Ciullo,Tanguy Corre,Tanguy Corre,Fergus J. Couch,Angela Cox,Laura Crisponi,Simon S. Cross,Francesco Cucca,Francesco Cucca,Kamila Czene,George Davey Smith,Eco J. C. de Geus,Eco J. C. de Geus,Renée de Mutsert,Immaculata De Vivo,Immaculata De Vivo,Ellen W. Demerath,Joe Dennis,Alison M. Dunning,Miriam Dwek,Mikael Eriksson,Tõnu Esko,Tõnu Esko,Peter A. Fasching,Peter A. Fasching,Jessica D. Faul,Luigi Ferrucci,Nora Franceschini,Timothy M. Frayling,Manuela Gago-Dominguez,Massimo Mezzavilla,Montserrat Garcia-Closas,Christian Gieger,Graham G. Giles,Graham G. Giles,Graham G. Giles,Harald Grallert,Daniel F. Gudbjartsson,Vilmundur Gudnason,Pascal Guénel,Christopher A. Haiman,Niclas Håkansson,Per Hall,Caroline Hayward,Chunyan He,Wei He,Gerardo Heiss,Miya Kudo Høffding,John L. Hopper,Jouke J. Hottenga,Jouke J. Hottenga,Frank B. Hu,Frank B. Hu,David G. Hunter,Mohammad Arfan Ikram,Rebecca D. Jackson,Micaella Joaquim,Esther M. John,Peter K. Joshi,David Karasik,Sharon L.R. Kardia,Christiana Kartsonaki,Robert Karlsson,Cari M. Kitahara,Ivana Kolcic,Charles Kooperberg,Peter Kraft,Allison W. Kurian,Zoltán Kutalik,Zoltán Kutalik,Martina La Bianca,Genevieve Lachance,Claudia Langenberg,Lenore J. Launer,Joop S.E. Laven,Debbie A Lawlor,Loic Le Marchand,Jingmei Li,Annika Lindblom,Annika Lindblom,Sara Lindström,Tricia Lindstrom,Martha S. Linet,Yongmei Liu,Simin Liu,Jian'an Luan,Reedik Mägi,Patrik K. E. Magnusson,Massimo Mangino,Massimo Mangino,Arto Mannermaa,Brumat Marco,Jonathan Marten,Nicholas G. Martin,Hamdi Mbarek,Hamdi Mbarek,Barbara McKnight,Sarah E. Medland,Christa Meisinger,Thomas Meitinger,Cristina Menni,Andres Metspalu,Lili Milani,Roger L. Milne,Roger L. Milne,Roger L. Milne,Grant W. Montgomery,Dennis O. Mook-Kanamori,Antonella Mulas,Anna Marie Mulligan,Anna Marie Mulligan,Alison D. Murray,Mike A. Nalls,Anne B. Newman,Raymond Noordam,Teresa Nutile,Dale R. Nyholt,Andrew F. Olshan,Håkan Olsson,Jodie N. Painter,Alpa V. Patel,Nancy L. Pedersen,Natalia Perjakova,Annette Peters,Ulrike Peters,Paul D.P. Pharoah,Ozren Polasek,Eleonora Porcu,Bruce M. Psaty,Iffat Rahman,Gad Rennert,Hedy S. Rennert,Paul M. Ridker,Paul M. Ridker,Susan M. Ring,Antonietta Robino,Lynda M. Rose,Frits R. Rosendaal,Jacques E. Rossouw,Igor Rudan,Rico Rueedi,Rico Rueedi,Daniela Ruggiero,Cinzia Sala,Emmanouil Saloustros,Dale P. Sandler,Serena Sanna,Elinor J. Sawyer,Chloé Sarnowski,David Schlessinger,Marjanka K. Schmidt,Minouk J. Schoemaker,Katharina E. Schraut,Katharina E. Schraut,Christopher G. Scott,Saleh Shekari,Amruta Shrikhande,Albert V. Smith,Blair H. Smith,Jennifer A. Smith,Rossella Sorice,Melissa C. Southey,Melissa C. Southey,Melissa C. Southey,Tim D. Spector,John J. Spinelli,Meir J. Stampfer,Meir J. Stampfer,Doris Stöckl,Joyce B. J. van Meurs,Konstantin Strauch,Konstantin Strauch,Unnur Styrkarsdottir,Anthony J. Swerdlow,Toshiko Tanaka,Lauren R. Teras,Alexander Teumer,Unnur Þorsteinsdottir,Unnur Þorsteinsdottir,Nicholas J. Timpson,Daniela Toniolo,Michela Traglia,Melissa A. Troester,Thérèse Truong,Jessica Tyrrell,André G. Uitterlinden,Sheila Ulivi,Celine M. Vachon,Veronique Vitart,Uwe Völker,Peter Vollenweider,Henry Völzke,Qin Wang,Nicholas J. Wareham,Clarice R. Weinberg,David R. Weir,Amber N. Wilcox,Ko Willems van Dijk,Gonneke Willemsen,Gonneke Willemsen,James F. Wilson,James F. Wilson,Bruce H. R. Wolffenbuttel,Alicja Wolk,Alicja Wolk,Andrew R. Wood,Wei Zhao,Marek Zygmunt,Zhengming Chen,Liming Li,Lude Franke,Stephen Burgess,Patrick Deelen,Patrick Deelen,Tune H. Pers,Marie Louise Grøndahl,Claus Yding Andersen,Anna Pujol,Andrés J. López-Contreras,Andrés J. López-Contreras,Jeremy A. Daniel,Kari Stefansson,Kari Stefansson,Jenny Chang-Claude,Jenny Chang-Claude,Yvonne T. van der Schouw,Kathryn L. Lunetta,Daniel I. Chasman,Daniel I. Chasman,Douglas F. Easton,Jenny A. Visser,Susan E. Ozanne,Satoshi H. Namekawa,Petr Solc,Joanne M. Murabito,Ken K. Ong,Eva Hoffmann,Anna Murray,Ignasi Roig,John R. B. Perry,John R. B. Perry +310 more
TL;DR: In this paper, the authors identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry.
Journal ArticleDOI
Multimodal biomedical AI
TL;DR: In this article , the authors outline the key applications enabled by multimodal artificial intelligence, along with the technical and analytical challenges, and survey the data, modeling and privacy challenges that must be overcome to realize the full potential of multimodAL artificial intelligence in health.
Journal ArticleDOI
Polygenic basis and biomedical consequences of telomere length variation.
Veryan Codd,Veryan Codd,Qingning Wang,Qingning Wang,Elias Allara,Elias Allara,Crispin Musicha,Crispin Musicha,Stephen Kaptoge,Stephen Kaptoge,Svetlana Stoma,Tao Jiang,Stephen E. Hamby,Stephen E. Hamby,Peter S. Braund,Vasiliki Bountziouka,Vasiliki Bountziouka,Charley A. Budgeon,Charley A. Budgeon,Charley A. Budgeon,Matthew Denniff,Chloe Swinfield,Manolo Papakonstantinou,Shilpi Sheth,Dominika E Nanus,Sophie C Warner,Minxian Wang,Minxian Wang,Amit Khera,James Eales,Willem H. Ouwehand,John R Thompson,Emanuele Di Angelantonio,Angela M. Wood,Adam S. Butterworth,John Danesh,Christopher P. Nelson,Christopher P. Nelson,Nilesh J. Samani,Nilesh J. Samani +39 more
TL;DR: In this paper, the authors characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants.
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
An integrated encyclopedia of DNA elements in the human genome
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Welch,Mary Kate Wing,Xiaowei Zhan,Philip Awadalla,Philip Awadalla,Alan Hodgkinson,Yun Li,Xinghua Shi,Andrew Quitadamo,Gerton Lunter,Jonathan Marchini,Simon Myers,Claire Churchhouse,Olivier Delaneau,Olivier Delaneau,Anjali Gupta-Hinch,Warren W. Kretzschmar,Zamin Iqbal,Iain Mathieson,Androniki Menelaou,Androniki Menelaou,Andy Rimmer,Dionysia Kiara Xifara,Taras K. Oleksyk,Yunxin Fu,Xiaoming Liu,Momiao Xiong,Lynn B. Jorde,David J. Witherspoon,Jinchuan Xing,Brian L. Browning,Sharon R. Browning,Fereydoun Hormozdiari,Peter H. Sudmant,Ekta Khurana,Chris Tyler-Smith,Cornelis A. Albers,Qasim Ayub,Yuan Chen,Vincenza Colonna,Vincenza Colonna,Luke Jostins,Klaudia Walter,Yali Xue,Mark Gerstein,Alexej Abyzov,Suganthi Balasubramanian,Jieming Chen,Declan Clarke,Yao Fu,Arif Harmanci,Mike Jin,Dong-Hoon Lee,Jeremy Liu,Xinmeng Jasmine Mu,Xinmeng Jasmine Mu,Jing Zhang,Yan Zhang,Christopher Hartl,Khalid Shakir,Jeremiah D. Degenhardt,Sascha Meiers,Benjamin Raeder,Francesco Paolo Casale,Oliver Stegle,Eric-Wubbo Lameijer,Ira M. Hall,Vineet Bafna,Jacob J. Michaelson,Eugene J. Gardner,Ryan E. Mills,Gargi Dayama,Ken Chen,Xian Fan,Zechen Chong,Tenghui Chen,Mark Chaisson,John Huddleston,Maika Malig,Bradley J. Nelson,Nicholas F. Parrish,Ben Blackburne,Sarah J. Lindsay,Zemin Ning,Yujun Zhang,Hugo Y. K. Lam,Cristina Sisu,Danny Challis,Uday S. Evani,James T. Lu,Uma Nagaswamy,Jin Yu,Wangshen Li,Lukas Habegger,Haiyuan Yu,Fiona Cunningham,Ian Dunham,Kasper Lage,Kasper Lage,Jakob Berg Jespersen,Jakob Berg Jespersen,Jakob Berg Jespersen,Heiko Horn,Heiko Horn,Donghoon Kim,Rob DeSalle,Apurva Narechania,Melissa A. Wilson Sayres,Fernando L. Mendez,G. David Poznik,Peter A. Underhill,David Mittelman,Ruby Banerjee,Maria Cerezo,Thomas W. Fitzgerald,Sandra Louzada,Andrea Massaia,Fengtang Yang,Divya Kalra,Walker Hale,Xu Dan,Kathleen C. Barnes,Christine Beiswanger,Hongyu Cai,Hongzhi Cao,Hongzhi Cao,Brenna M. Henn,Danielle Jones,Jane Kaye,Alastair Kent,Angeliki Kerasidou,Rasika A. Mathias,Pilar N. Ossorio,Michael Parker,Charles N. Rotimi,Charmaine D.M. Royal,Karla Sandoval,Yeyang Su,Zhongming Tian,Sarah A. Tishkoff,Marc Via,Yuhong Wang,Huanming Yang,Ling Yang,Jiayong Zhu,Walter F. Bodmer,Gabriel Bedoya,Zhiming Cai,Yang Gao,Jiayou Chu,Leena Peltonen,Andrés C. García-Montero,Alberto Orfao,Julie Dutil,Juan Carlos Martínez-Cruzado,R. Mathias,Anselm Hennis,Harold Watson,Colin A. McKenzie,Firdausi Qadri,Regina C. LaRocque,Xiaoyan Deng,Danny Asogun,Onikepe A. Folarin,Christian T. Happi,Omonwunmi Omoniwa,Matt Stremlau,Matt Stremlau,Ridhi Tariyal,Ridhi Tariyal,M Jallow,M Jallow,Fatoumatta Sisay Joof,Fatoumatta Sisay Joof,Tumani Corrah,Tumani Corrah,Kirk A. Rockett,Kirk A. Rockett,Dominic P. Kwiatkowski,Dominic P. Kwiatkowski,Jaspal S. Kooner,Tran Tinh Hien,Sarah J. Dunstan,Sarah J. Dunstan,Nguyen ThuyHang,Richard Fonnie,Robert F. Garry,Lansana Kanneh,Lina M. Moses,John S. Schieffelin,Donald S. Grant,Carla Gallo,Giovanni Poletti,Danish Saleheen,Asif Rasheed,Lisa D. Brooks,Adam Felsenfeld,Jean E. McEwen,Yekaterina Vaydylevich,Audrey Duncanson,Michael Dunn,Jeffery A. Schloss +517 more
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Journal ArticleDOI
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
Paul Burton,David Clayton,Lon R. Cardon,Nicholas John Craddock,Panos Deloukas,Audrey Duncanson,Dominic P. Kwiatkowski,Mark I. McCarthy,Willem H. Ouwehand,Nilesh J. Samani,John A. Todd,Peter Donnelly,Jeffrey C. Barrett,Dan Davison,Doug Easton,David M. Evans,H. T. Leung,Jonathan Marchini,Andrew P. Morris,Chris C. A. Spencer,Martin D. Tobin,Antony P. Attwood,James P. Boorman,Barbara Cant,Ursula Everson,Judith M. Hussey,Jennifer Jolley,Alexandra S. Knight,Kerstin Koch,Elizabeth Meech,Sarah Nutland,Christopher Prowse,Helen Stevens,Niall C. Taylor,Graham R. Walters,Neil Walker,Nicholas A. Watkins,Thilo Winzer,Richard Jones,Wendy L. McArdle,Susan M. Ring,David P. Strachan,Marcus Pembrey,Gerome Breen,David St Clair,Sian Caesar,Katherine Gordon-Smith,Lisa Jones,Christine Fraser,Elaine K. Green,Detelina Grozeva,Marian L. Hamshere,Peter Holmans,Ian Jones,George Kirov,Valentina Moskvina,Ivan Nikolov,Michael Conlon O'Donovan,Michael John Owen,David A. Collier,Amanda Elkin,Anne Farmer,Richard Williamson,Peter McGuffin,Allan H. Young,I. Nicol Ferrier,Stephen G. Ball,Anthony J. Balmforth,Jennifer H. Barrett,D. Timothy Bishop,Mark M. Iles,Azhar Maqbool,Nadira Yuldasheva,Alistair S. Hall,Peter S. Braund,Richard J. Dixon,Massimo Mangino,Suzanne Stevens,John R. Thompson,Francesca Bredin,Mark Tremelling,Miles Parkes,Hazel E. Drummond,Charlie W. Lees,Elaine R. Nimmo,Jack Satsangi,Sheila A. Fisher,Alastair Forbes,Cathryn M. Lewis,Clive M. Onnie,Natalie J. Prescott,Jeremy D. Sanderson,Christopher G. Mathew,Jamie Barbour,M. Khalid Mohiuddin,Catherine E. Todhunter,John C. Mansfield,Tariq Ahmad,Fraser Cummings,Derek P. Jewell,John Webster,Morris J. Brown,G. Mark Lathrop,John M. C. Connell,Anna F. Dominiczak,Carolina A. Braga Marcano,Beverley Burke,Richard Dobson,Johannie Gungadoo,Kate L. Lee,Patricia B. Munroe,Stephen Newhouse,Abiodun Onipinla,Chris Wallace,Mingzhan Xue,Mark J. Caulfield,Martin Farrall,Anne Barton,Ian N. Bruce,Hannah Donovan,Steve Eyre,Paul D. Gilbert,Samantha L. Hider,Anne Hinks,Sally John,Catherine Potter,Alan J. Silman,Deborah P M Symmons,Wendy Thomson,Jane Worthington,David B. Dunger,Barry Widmer,Timothy M. Frayling,Rachel M. Freathy,Hana Lango,John R. B. Perry,Beverley M. Shields,Michael N. Weedon,Andrew T. Hattersley,Graham A. Hitman,Mark Walker,Kate S. Elliott,Christopher J. Groves,Cecilia M. Lindgren,Nigel W. Rayner,Nicholas J. Timpson,Eleftheria Zeggini,Melanie J. Newport,Giorgio Sirugo,Emily J. Lyons,Fredrik O. Vannberg,Adrian V. S. Hill,Linda A. Bradbury,C Farrar,J J Pointon,Paul Wordsworth,Matthew A. Brown,Jayne A. Franklyn,Joanne M. Heward,Matthew J. Simmonds,Stephen C. L. Gough,Sheila Seal,Michael R. Stratton,Nazneen Rahman,Maria Ban,An Goris,Stephen Sawcer,Alastair Compston,David J. Conway,Muminatou Jallow,Kirk A. Rockett,Suzannah Bumpstead,Amy Chaney,Kate Downes,Mohammed J. R. Ghori,Rhian Gwilliam,Sarah E. Hunt,Michael Inouye,Andrew Keniry,Emma King,Ralph McGinnis,Simon C. Potter,Rathi Ravindrarajah,Pamela Whittaker,Claire Widden,David Withers,Niall Cardin,Teresa Ferreira,Joanne Pereira-Gale,Ingileif B. Hallgrímsdóttir,Bryan Howie,Zhan Su,Yik Ying Teo,Damjan Vukcevic,David Bentley,A Compston +195 more
TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Journal ArticleDOI
The mutational constraint spectrum quantified from variation in 141,456 humans
Konrad J. Karczewski,Laurent C. Francioli,Grace Tiao,Beryl B. Cummings,Jessica Alföldi,Qingbo Wang,Ryan L. Collins,Kristen M. Laricchia,Andrea Ganna,Daniel P. Birnbaum,Laura D. Gauthier,Harrison Brand,Matthew Solomonson,Nicholas A. Watts,Daniel R. Rhodes,Moriel Singer-Berk,Eleina M. England,Eleanor G. Seaby,Jack A. Kosmicki,Raymond K. Walters,Katherine Tashman,Yossi Farjoun,Eric Banks,Timothy Poterba,Arcturus Wang,Cotton Seed,Nicola Whiffin,Jessica X. Chong,Kaitlin E. Samocha,Emma Pierce-Hoffman,Zachary Zappala,Anne H. O’Donnell-Luria,Eric Vallabh Minikel,Ben Weisburd,Monkol Lek,James S. Ware,Christopher Vittal,Irina M. Armean,Louis Bergelson,Kristian Cibulskis,Kristen M. Connolly,Miguel Covarrubias,Stacey Donnelly,Steven Ferriera,Stacey Gabriel,Jeff Gentry,Namrata Gupta,Thibault Jeandet,Diane Kaplan,Christopher Llanwarne,Ruchi Munshi,Sam Novod,Nikelle Petrillo,David Roazen,Valentin Ruano-Rubio,Andrea Saltzman,Molly Schleicher,Jose Soto,Kathleen Tibbetts,Charlotte Tolonen,Gordon Wade,Michael E. Talkowski,Benjamin M. Neale,Mark J. Daly,Daniel G. MacArthur +64 more
TL;DR: A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.
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The mutational constraint spectrum quantified from variation in 141,456 humans
Konrad J. Karczewski,Laurent C. Francioli,Grace Tiao,Beryl B. Cummings,Jessica Alföldi,Qingbo Wang,Ryan L. Collins,Kristen M. Laricchia,Andrea Ganna,Daniel P. Birnbaum,Laura D. Gauthier,Harrison Brand,Matthew Solomonson,Nicholas A. Watts,Daniel R. Rhodes,Moriel Singer-Berk,Eleina M. England,Eleanor G. Seaby,Jack A. Kosmicki,Raymond K. Walters,Katherine Tashman,Yossi Farjoun,Eric Banks,Timothy Poterba,Arcturus Wang,Cotton Seed,Nicola Whiffin,Jessica X. Chong,Kaitlin E. Samocha,Emma Pierce-Hoffman,Zachary Zappala,Anne H. O’Donnell-Luria,Eric Vallabh Minikel,Ben Weisburd,Monkol Lek,James S. Ware,Christopher Vittal,Irina M. Armean,Louis Bergelson,Kristian Cibulskis,Kristen M. Connolly,Miguel Covarrubias,Stacey Donnelly,Steven Ferriera,Stacey Gabriel,Jeff Gentry,Namrata Gupta,Thibault Jeandet,Diane Kaplan,Christopher Llanwarne,Ruchi Munshi,Sam Novod,Nikelle Petrillo,David Roazen,Valentin Ruano-Rubio,Andrea Saltzman,Molly Schleicher,Jose Soto,Kathleen Tibbetts,Charlotte Tolonen,Gordon Wade,Michael E. Talkowski,Benjamin M. Neale,Mark J. Daly,Daniel G. MacArthur +64 more