Journal ArticleDOI
Benefits and limitations of genome-wide association studies.
Vivian W.Y. Tam,Nikunj Patel,Michelle Turcotte,Yohan Bossé,Guillaume Paré,David Meyre,David Meyre +6 more
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TLDR
This Review comprehensively assess the benefits and limitations of GWAS in human populations and discusses the relevance of performing more GWAS, with a focus on the cardiometabolic field.Abstract:
Genome-wide association studies (GWAS) involve testing genetic variants across the genomes of many individuals to identify genotype–phenotype associations. GWAS have revolutionized the field of complex disease genetics over the past decade, providing numerous compelling associations for human complex traits and diseases. Despite clear successes in identifying novel disease susceptibility genes and biological pathways and in translating these findings into clinical care, GWAS have not been without controversy. Prominent criticisms include concerns that GWAS will eventually implicate the entire genome in disease predisposition and that most association signals reflect variants and genes with no direct biological relevance to disease. In this Review, we comprehensively assess the benefits and limitations of GWAS in human populations and discuss the relevance of performing more GWAS. Despite the success of human genome-wide association studies (GWAS) in associating genetic variants and complex diseases or traits, criticisms of the usefulness of this study design remain. This Review assesses the pros and cons of GWAS, with a focus on the cardiometabolic field.read more
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Integrative analysis of 111 reference human epigenomes
Anshul Kundaje,Wouter Meuleman,Jason Ernst,Angela Yen,Pouya Kheradpour,Zhizhuo Zhang,Jianrong Wang,Lucas D. Ward,Abhishek Sarkar,Gerald Quon,Matthew L. Eaton,Yi-Chieh Wu,Andreas R. Pfenning,Xinchen Wang,Melina Claussnitzer,Yaping Liu,Mukul S. Bansal,Soheil Feizi-Khankandi,Ah Ram Kim,Richard C Sallari,Nicholas A Sinnott-Armstrong,Laurie A. Boyer,Elizabeta Gjoneska,Li-Huei Tsai,Manolis Kellis +24 more
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Hana Lango Allen,Karol Estrada,Guillaume Lettre,Sonja I. Berndt,Michael N. Weedon,Fernando Rivadeneira,Cristen J. Willer,Anne U. Jackson,Sailaja Vedantam,Soumya Raychaudhuri,Teresa Ferreira,Andrew R. Wood,Robert J. Weyant,Ayellet V. Segrè,Elizabeth K. Speliotes,Eleanor Wheeler,Nicole Soranzo,Ju-Hyun Park,Jian Yang,Daniel F. Gudbjartsson,Nancy L. Heard-Costa,Joshua C. Randall,Lu Qi,Albert V. Smith,Reedik Maegi,Tomi Pastinen,Liming Liang,Iris M. Heid,Jian'an Luan,Gudmar Thorleifsson,Thomas W. Winkler,Michael E. Goddard,Ken Sin Lo,Cameron D. Palmer,Tsegaselassie Workalemahu,Yurii S. Aulchenko,Åsa Johansson,M. Carola Zillikens,Mary F. Feitosa,Tõnu Esko,Toby Johnson,Shamika Ketkar,Peter Kraft,Massimo Mangino,Inga Prokopenko,Devin Absher,Eva Albrecht,Florian Ernst,Nicole L. Glazer,Caroline Hayward,Jouke-Jan Hottenga,Kevin B. Jacobs,Joshua W. Knowles,Zoltán Kutalik,Keri L. Monda,Ozren Polasek,Michael Preuss,Nigel W. Rayner,Neil R. Robertson,Valgerdur Steinthorsdottir,Jonathan Tyrer,Benjamin F. Voight,Fredrik Wiklund,Jianfeng Xu,Jing Hua Zhao,Dale R. Nyholt,Niina Pellikka,Markus Perola,John R. B. Perry,Ida Surakka,Mari-Liis Tammesoo,Elizabeth L. Altmaier,Najaf Amin,Thor Aspelund,Tushar Bhangale,Gabrielle Boucher,Daniel I. Chasman,Constance Chen,Lachlan J. M. Coin,Mark E. Cooper,Anna L. Dixon,Quince Gibson,Elin Grundberg,Ke Hao,M. Juhani Junttila,Lee M. Kaplan,Johannes Kettunen,Inke R. Koenig,Tony Kwan,Robert Lawrence,Douglas F. Levinson,Mattias Lorentzon,Barbara McKnight,Andrew P. Morris,Martina Mueller,Julius S. Ngwa,Shaun Purcell,Suzanne Rafelt,Rany M. Salem,Erika Salvi,Serena Sanna,Jianxin Shi,Ulla Sovio,John R. Thompson,Michael C. Turchin,Liesbeth Vandenput,Dominique J. Verlaan,Veronique Vitart,Charles C. White,Andreas Ziegler,Peter Almgren,Anthony J. Balmforth,Harry Campbell,Lorena Citterio,Alessandro De Grandi,Anna F. Dominiczak,Jubao Duan,Paul Elliott,Roberto Elosua,Johan G. Eriksson,Nelson B. Freimer,Eco J. C. de Geus,Nicola Glorioso,Shen Haiqing,Anna-Liisa Hartikainen,Aki S. Havulinna,Andrew A. Hicks,Jennie Hui,Wilmar Igl,Thomas Illig,Antti Jula,Eero Kajantie,Tuomas O. Kilpelaeinen,Markku Koiranen,Ivana Kolcic,Seppo Koskinen,Peter Kovacs,Jaana Laitinen,Jianjun Liu,Marja-Liisa Lokki,Ana Marušić,Andrea Maschio,Thomas Meitinger,Antonella Mulas,Guillaume Paré,Alex N. Parker,John F. Peden,Astrid Petersmann,Irene Pichler,Kirsi H. Pietiläinen,Anneli Pouta,Martin Riddertrale,Jerome I. Rotter,Jennifer G. Sambrook,Alan R. Sanders,Carsten Oliver Schmidt,Juha Sinisalo,Jan Smit,Heather M. Stringham,G. Bragi Walters,Elisabeth Widen,Sarah H. Wild,Gonneke Willemsen,Laura Zagato,Lina Zgaga,Paavo Zitting,Helene Alavere,Martin Farrall,Wendy L. McArdle,Mari Nelis,Marjolein Peters,Samuli Ripatti,Joyce B. J. vVan Meurs,Katja K.H. Aben,Kristin G. Ardlie,Jacques S. Beckmann,John Beilby,Richard N. Bergman,Sven Bergmann,Francis S. Collins,Daniele Cusi,Martin den Heijer,Gudny Eiriksdottir,Pablo V. Gejman,Alistair S. Hall,Anders Hamsten,Heikki V. Huikuri,Carlos Iribarren,Mika Kähönen,Jaakko Kaprio,Sekar Kathiresan,Lambertus A. Kiemeney,Thomas D. Kocher,Lenore J. Launer,Terho Lehtimäki,Olle Melander,Thomas H. Mosley,Arthur W. Musk,Markku S. Nieminen,Christopher J. O'Donnell,Claes Ohlsson,Ben A. Oostra,Lyle J. Palmer,Olli T. Raitakari,Paul M. Ridker,John D. Rioux,Aila Rissanen,Carlo Rivolta,Heribert Schunkert,Alan R. Shuldiner,David S. Siscovick,Michael Stumvoll,Anke Toenjes,Jaakko Tuomilehto,Gert-Jan B. van Ommen,Jorma Viikari,Andrew C. Heath,Nicholas G. Martin,Grant W. Montgomery,Michael A. Province,Manfred Kayser,Alice M. Arnold,Larry D. Atwood,Eric Boerwinkle,Stephen J. Chanock,Panos Deloukas,Christian Gieger,Henrik Grönberg,Per Hall,Andrew T. Hattersley,Christian Hengstenberg,Wolfgang Hoffman,G. Mark Lathrop,Veikko Salomaa,Stefan Schreiber,Manuela Uda,Dawn M. Waterworth,Alan F. Wright,Themistocles L. Assimes,Inês Barroso,Albert Hofman,Karen L. Mohlke,Dorret I. Boomsma,Mark J. Caulfield,L. Adrienne Cupples,Jeanette Erdmann,Caroline S. Fox,Vilmundur Gudnason,Ulf Gyllensten,Tamara B. Harris,Richard B. Hayes,Marjo-Ritta Jarvelin,Vincent Mooser,Patricia B. Munroe,Willem H. Ouwehand,Brenda W.J.H. Penninx,Peter P. Pramstaller,Thomas Quertermous,Igor Rudan,Nilesh J. Samani,Tim D. Spector,Henry Voelzke,Hugh Watkins,James F. Wilson,Leif Groop,Talin Haritunians,Frank B. Hu,Robert C. Kaplan,Andres Metspalu,Kari E. North,David Schlessinger,Nicholas J. Wareham,David J. Hunter,Jeffrey R. O'Connell,David P. Strachan,H. Erich Schadt,Unnur Thorsteinsdottir,Leena Peltonen,André G. Uitterlinden,Peter M. Visscher,Nilanjan Chatterjee,Ruth J. F. Loos,Michael Boehnke,Mark I. McCarthy,Erik Ingelsson,Cecilia M. Lindgren,Gonçalo R. Abecasis,Kari Stefansson,Timothy M. Frayling,Joel N. Hirschhorn +289 more
TL;DR: In this paper, the authors show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, revealing patterns with important implications for genetic studies of common human diseases and traits.
The Answer Is 17 Years, What Is the Question
TL;DR: The study concludes that understanding lags first requires agreeing models, definitions and measures, which can be applied in practice, and a second task would be to develop a process by which to gather these data.
The genetic architecture of type 2 diabetes
Christian Fuchsberger,Jason Flannick,Tanya M. Teslovich,Anubha Mahajan,Vineeta Agarwala,Kyle J. Gaulton,Clement Ma,Pierre Fontanillas,Loukas Moutsianas,Davis J. McCarthy,Manuel A. Rivas,John R. B. Perry,Xueling Sim,Thomas W. Blackwell,Neil Robertson,N. William Rayner,Pablo Cingolani,Adam E. Locke,Juan Fernandez Tajes,Heather M. Highland,Josée Dupuis,Peter S. Chines,Cecilia M. Lindgren,Christopher Hartl,Anne U. Jackson,Han Chen,Jeroen R. Huyghe,Martijn van de Bunt,Richard D. Pearson,Ashok Kumar,Martina Mueller-Nurasyid,Niels Grarup,Heather M. Stringham,Eric R. Gamazon,Jae-Hoon Lee,Yi Chen,Robert A. Scott,Jennifer E. Below,Peng Chen,Jinyan Huang,Min Jin Go,Michael L. Stitzel,Dorota Pasko,Stephen C. J. Parker,Tibor V. Varga,Todd Green,Nicola L. Beer,Aaron G. Day-Williams,Teresa Ferreira,Tasha E. Fingerlin,Momoko Horikoshi,Cheng Hu,Iksoo Huh,Mohammad Kamran Ikram,Bong-Jo Kim,Yongkang Kim,Young-Jin Kim,Min-Seok Kwon,Juyoung Lee,Selyeong Lee,Keng-Han Lin,Taylor J. Maxwell,Yoshihiko Nagai,Xu Wang,Ryan P. Welch,Joon Yoon,Weihua Zhang,Nir Barzilai,Benjamin F. Voight,Bok-Ghee Han,Christopher P. Jenkinson,Teemu Kuulasmaa,Johanna Kuusisto,Alisa K. Manning,Maggie C.Y. Ng,Nicholette D. Palmer,Beverley Balkau,Alena Stančáková,Hanna E. Abboud,Heiner Boeing,Vilmantas Giedraitis,Dorairaj Prabhakaran,Omri Gottesman,James Scott,Jason Carey,Phoenix Kwan,George B. Grant,Joshua D. Smith,Benjamin M. Neale,Shaun Purcell,Adam S. Butterworth,Joanna M. M. Howson,Heung Man Lee,Yingchang Lu,Soo Heon Kwak,Wei Zhao,John Danesh,Vincent K. L. Lam,Kyong Soo Park,Danish Saleheen,Wing-Yee So,Claudia H. T. Tam,Uzma Afzal,David Aguilar,Rector Arya,Tin Aung,Edmund Chan,Carmen Navarro,Ching-Yu Cheng,Domenico Palli,Adolfo Correa,Joanne E. Curran,Denis Rybin,Vidya S. Farook,Sharon P. Fowler,Barry I. Freedman,Michael Griswold,Daniel E. Hale,Pamela J. Hicks,Chiea Chuen Khor,Satish Kumar,Benjamin Lehne,Dorothée Thuillier,Wei-Yen Lim,Jianjun Liu,Yvonne T. van der Schouw,Marie Loh,Solomon K. Musani,Sobha Puppala,William R. Scott,Loic Yengo,Sian-Tsung Tan,Herman A. Taylor,Farook Thameem,Gregory P. Wilson,Tien Yin Wong,Pål R. Njølstad,Jonathan C. Levy,Massimo Mangino,Lori L. Bonnycastle,Thomas Schwarzmayr,João Fadista,Gabriela L. Surdulescu,Christian Herder,Christopher J. Groves,Thomas Wieland,Jette Bork-Jensen,Ivan Brandslund,Cramer Christensen,Heikki A. Koistinen,Alex S. F. Doney,Leena Kinnunen,Tõnu Esko,Andrew Farmer,Liisa Hakaste,Dylan Hodgkiss,Jasmina Kravic,Valeriya Lyssenko,Mette Hollensted,Marit E. Jørgensen,Torben Jørgensen,Claes Ladenvall,Johanne Marie Justesen,Annemari Käräjämäki,Jennifer Kriebel,Wolfgang Rathmann,Lars Lannfelt,Torsten Lauritzen,Narisu Narisu,Allan Linneberg,Olle Melander,Lili Milani,Matt Neville,Marju Orho-Melander,Lu Qi,Qibin Qi,Michael Roden,Olov Rolandsson,Amy J. Swift,Anders Rosengren,Kathleen Stirrups,Andrew R. Wood,Evelin Mihailov,Christine Blancher,Mauricio O. Carneiro,Jared Maguire,Ryan Poplin,Khalid Shakir,Timothy R. Fennell,Mark A. DePristo,Martin Hrabé de Angelis,Panos Deloukas,Anette P. Gjesing,Goo Jun,Peter M. Nilsson,Jacquelyn Murphy,Robert C. Onofrio,Barbara Thorand,Torben Hansen,Christa Meisinger,Frank B. Hu,Bo Isomaa,Fredrik Karpe,Liming Liang,Annette Peters,Cornelia Huth,Stephen O'Rahilly,Colin N. A. Palmer,Oluf Pedersen,Rainer Rauramaa,Jaakko Tuomilehto,Veikko Salomaa,Richard M. Watanabe,Ann-Christine Syvänen,Richard N. Bergman,Dwaipayan Bharadwaj,Erwin P. Bottinger,Yoon Shin Cho,Giriraj R. Chandak,Juliana C.N. Chan,Kee Seng Chia,Mark J. Daly,Shah Ebrahim,Claudia Langenberg,Paul Elliott,Kathleen A. Jablonski,Donna M. Lehman,Weiping Jia,Ronald C.W. Ma,Toni I. Pollin,Manjinder S. Sandhu,Nikhil Tandon,Philippe Froguel,Inês Barroso,Yik Ying Teo,Eleftheria Zeggini,Ruth J. F. Loos,Kerrin S. Small,Janina S. Ried,Ralph A. DeFronzo,Harald Grallert,Benjamin Glaser,Andres Metspalu,Nicholas J. Wareham,Mark Walker,Eric Banks,Christian Gieger,Erik Ingelsson,Hae Kyung Im,Thomas Illig,Paul W. Franks,Gemma Buck,Joseph Trakalo,David Buck,Inga Prokopenko,Reedik Mägi,Lars Lind,Yossi Farjoun,Katharine R. Owen,Anna L. Gloyn,Konstantin Strauch,Tiinamaija Tuomi,Jaspal S. Kooner,Jong-Young Lee,Taesung Park,Peter Donnelly,Andrew D. Morris,Andrew T. Hattersley,Donald W. Bowden,Francis S. Collins,Gil Atzmon,John C. Chambers,Tim D. Spector,Markku Laakso,Tim M. Strom,Graeme I. Bell,John Blangero,Ravindranath Duggirala,E. Shyong Tai,Gilean McVean,Craig L. Hanis,James G. Wilson,Mark Seielstad,Timothy M. Frayling,James B. Meigs,Nancy J. Cox,Robert Sladek,Eric S. Lander,Stacey Gabriel,Noël P. Burtt,Karen L. Mohlke,Thomas Meitinger,Leif Groop,Gonçalo R. Abecasis,Jose C. Florez,Laura J. Scott,Andrew P. Morris,Hyun Min Kang,Michael Boehnke,David Altshuler,Mark I. McCarthy +300 more
TL;DR: Large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes, but most fell within regions previously identified by genome-wide association studies.
Loss-of-function mutations in SLC30A8 protect against type 2 diabetes
Jason Flannick,Gudmar Thorleifsson,Nicola L. Beer,Suzanne B.R. Jacobs,Niels Grarup,Noël P. Burtt,Anubha Mahajan,Christian Fuchsberger,Gil Atzmon,Rafn Benediktsson,John Blangero,Donald W. Bowden,Ivan Brandslund,Julia Brosnan,Frank Burslem,John C. Chambers,Yoon Shin Cho,Cramer Christensen,Desiree Douglas,Ravindranath Duggirala,Zachary Dymek,Yossi Farjoun,Timothy Fennell,Pierre Fontanillas,Tom Forsén,Stacey Gabriel,Benjamin Glaser,Daniel F. Gudbjartsson,Craig L. Hanis,Torben Hansen,Astradur B. Hreidarsson,Kristian Hveem,Erik Ingelsson,Bo Isomaa,Stefan Johansson,Torben Jørgensen,Marit E. Jørgensen,Sekar Kathiresan,Augustine Kong,Jaspal S. Kooner,Jasmina Kravic,Markku Laakso,Jong-Young Lee,Lars Lind,Cecilia M. Lindgren,Allan Linneberg,Gisli Masson,Thomas Meitinger,Karen L. Mohlke,Anders Molven,Andrew P. Morris,Shobha Potluri,Rainer Rauramaa,Rasmus Ribel-Madsen,Ann-Marie Richard,Tim Rolph,Veikko Salomaa,Ayellet V. Segrè,Hanna Skaerstrand,Valgerdur Steinthorsdottir,Heather M. Stringham,Patrick Sulem,E. Shyong Tai,Yik Ying Teo,Tanya M. Teslovich,Unnur Thorsteinsdottir,Jeff K. Trimmer,Tiinamaija Tuomi,Jaakko Tuomilehto,Fariba Vaziri-Sani,Benjamin F. Voight,James G. Wilson,Michael Boehnke,Mark I. McCarthy,Pål R. Njølstad,Oluf Pedersen,Leif Groop,David Cox,Kari Stefansson,David Altshuler +79 more
TL;DR: Loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against type 2 diabetes, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
References
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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
Analysis of protein-coding genetic variation in 60,706 humans
Monkol Lek,Konrad J. Karczewski,Konrad J. Karczewski,Eric Vallabh Minikel,Eric Vallabh Minikel,Kaitlin E. Samocha,Eric Banks,Timothy Fennell,Anne H. O’Donnell-Luria,Anne H. O’Donnell-Luria,Anne H. O’Donnell-Luria,James S. Ware,Andrew J. Hill,Andrew J. Hill,Andrew J. Hill,Beryl B. Cummings,Beryl B. Cummings,Taru Tukiainen,Taru Tukiainen,Daniel P. Birnbaum,Jack A. Kosmicki,Laramie E. Duncan,Laramie E. Duncan,Karol Estrada,Karol Estrada,Fengmei Zhao,Fengmei Zhao,James Zou,Emma Pierce-Hoffman,Emma Pierce-Hoffman,Joanne Berghout,David Neil Cooper,Nicole A. Deflaux,Mark A. DePristo,Ron Do,Jason Flannick,Jason Flannick,Menachem Fromer,Laura D. Gauthier,Jackie Goldstein,Jackie Goldstein,Namrata Gupta,Daniel P. Howrigan,Daniel P. Howrigan,Adam Kiezun,Mitja I. Kurki,Mitja I. Kurki,Ami Levy Moonshine,Pradeep Natarajan,Lorena Orozco,Gina M. Peloso,Gina M. Peloso,Ryan Poplin,Manuel A. Rivas,Valentin Ruano-Rubio,Samuel A. Rose,Douglas M. Ruderfer,Khalid Shakir,Peter D. Stenson,Christine Stevens,Brett Thomas,Brett Thomas,Grace Tiao,María Teresa Tusié-Luna,Ben Weisburd,Hong-Hee Won,Dongmei Yu,David Altshuler,David Altshuler,Diego Ardissino,Michael Boehnke,John Danesh,Stacey Donnelly,Roberto Elosua,Jose C. Florez,Jose C. Florez,Stacey Gabriel,Gad Getz,Gad Getz,Stephen J. Glatt,Christina M. Hultman,Sekar Kathiresan,Markku Laakso,Steven A. McCarroll,Steven A. McCarroll,Mark I. McCarthy,Mark I. McCarthy,Dermot P.B. McGovern,Ruth McPherson,Benjamin M. Neale,Benjamin M. Neale,Aarno Palotie,Shaun Purcell,Danish Saleheen,Jeremiah M. Scharf,Pamela Sklar,Patrick F. Sullivan,Patrick F. Sullivan,Jaakko Tuomilehto,Ming T. Tsuang,Hugh Watkins,Hugh Watkins,James G. Wilson,Mark J. Daly,Mark J. Daly,Daniel G. MacArthur,Daniel G. MacArthur +106 more
TL;DR: The aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC) provides direct evidence for the presence of widespread mutational recurrence.
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