Estimation of effect size distribution from genome-wide association studies and implications for future discoveries
Ju-Hyun Park,Sholom Wacholder,Mitchell H. Gail,Ulrike Peters,Kevin B. Jacobs,Stephen J. Chanock,Nilanjan Chatterjee +6 more
TLDR
Using reported GWAS findings for height, Crohn's disease and breast, prostate and colorectal cancers, it is determined that each of these traits is likely to harbor additional loci within the spectrum of low-penetrance common variants.Abstract:
We report a set of tools to estimate the number of susceptibility loci and the distribution of their effect sizes for a trait on the basis of discoveries from existing genome-wide association studies (GWASs). We propose statistical power calculations for future GWASs using estimated distributions of effect sizes. Using reported GWAS findings for height, Crohn's disease and breast, prostate and colorectal (BPC) cancers, we determine that each of these traits is likely to harbor additional loci within the spectrum of low-penetrance common variants. These loci, which can be identified from sufficiently powerful GWASs, together could explain at least 15-20% of the known heritability of these traits. However, for BPC cancers, which have modest familial aggregation, our analysis suggests that risk models based on common variants alone will have modest discriminatory power (63.5% area under curve), even with new discoveries.read more
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Journal ArticleDOI
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
Elizabeth K. Speliotes,Elizabeth K. Speliotes,Cristen J. Willer,Sonja I. Berndt,Keri L. Monda,Gudmar Thorleifsson,Anne U. Jackson,Hana Lango Allen,Cecilia M. Lindgren,Jian'an Luan,Reedik Maegi,Joshua C. Randall,Sailaja Vedantam,Thomas W. Winkler,Lu Qi,Lu Qi,Tsegaselassie Workalemahu,Iris M. Heid,Valgerdur Steinthorsdottir,Heather M. Stringham,Michael N. Weedon,Eleanor Wheeler,Andrew R. Wood,Teresa Ferreira,Robert J. Weyant,Ayellet V. Segrè,Ayellet V. Segrè,Karol Estrada,Liming Liang,James Nemesh,James Nemesh,Ju-Hyun Park,Stefan Gustafsson,Tuomas O. Kilpelaenen,Jian Yang,Nabila Bouatia-Naji,Nabila Bouatia-Naji,Tõnu Esko,Mary F. Feitosa,Zoltán Kutalik,Massimo Mangino,Soumya Raychaudhuri,Soumya Raychaudhuri,Soumya Raychaudhuri,André Scherag,Albert V. Smith,Ryan P. Welch,Jing Hua Zhao,Katja K.H. Aben,Devin Absher,Najaf Amin,Anna L. Dixon,Eva Fisher,Nicole L. Glazer,Michael E. Goddard,Nancy L. Heard-Costa,Volker Hoesel,Jouke-Jan Hottenga,Åsa Johansson,Åsa Johansson,Toby Johnson,Shamika Ketkar,Claudia Lamina,Shengxu Li,Miriam F. Moffatt,Richard H. Myers,Narisu Narisu,John R. B. Perry,Marjolein Peters,Michael Preuss,Samuli Ripatti,Fernando Rivadeneira,Camilla H. Sandholt,Laura J. Scott,Nicholas J. Timpson,Jonathan Tyrer,Sophie van Wingerden,Richard M. Watanabe,Charles C. White,Fredrik Wiklund,Christina Barlassina,Daniel I. Chasman,Daniel I. Chasman,Mark E. Cooper,John-Olov Jansson,Robert Lawrence,Niina Pellikka,Inga Prokopenko,Jianxin Shi,Elisabeth Thiering,Helene Alavere,Maria Teresa Sciarrone Alibrandi,Peter Almgren,Alice M. Arnold,Thor Aspelund,Larry D. Atwood,Beverley Balkau,Anthony J. Balmforth,Amanda J. Bennett,Yoav Ben-Shlomo,Richard N. Bergman,Sven Bergmann,Heike Biebermann,Alexandra I. F. Blakemore,Tanja Boes,Lori L. Bonnycastle,Stefan R. Bornstein,Morris Brown,Thomas A. Buchanan,Fabio Busonero,Harry Campbell,Francesco P. Cappuccio,Christine Cavalcanti-Proença,Christine Cavalcanti-Proença,Yii-Der Ida Chen,Chih-Mei Chen,Peter S. Chines,Robert Clarke,Lachlan J. M. Coin,John M. C. Connell,Ian N. M. Day,Martin den Heijer,Jubao Duan,Shah Ebrahim,Paul Elliott,Roberto Elosua,Gudny Eiriksdottir,Michael R. Erdos,Johan G. Eriksson,Maurizio F. Facheris,Stephan B. Felix,Pamela Fischer-Posovszky,Aaron R. Folsom,Aaron R. Folsom,Nele Friedrich,Nelson B. Freimer,Mao Fu,Stefan Gaget,Stefan Gaget,Pablo V. Gejman,Eco J. C. de Geus,Christian Gieger,Anette P. Gjesing,Anuj Goel,Philippe Goyette,Harald Grallert,Juergen Graessler,Danielle M. Greenawalt,Christopher J. Groves,Vilmundur Gudnason,Candace Guiducci,Anna-Liisa Hartikainen,Neelam Hassanali,Alistair S. Hall,Aki S. Havulinna,Caroline Hayward,Andrew C. Heath,Christian Hengstenberg,Andrew A. Hicks,Anke Hinney,Albert Hofman,Georg Homuth,Jennie Hui,Wilmar Igl,Carlos Iribarren,Carlos Iribarren,Bo Isomaa,Kevin B. Jacobs,Ivonne Jarick,Elizabeth S. Jewell,Ulrich John,Torben Jørgensen,Pekka Jousilahti,Antti Jula,Marika Kaakinen,Eero Kajantie,Lee M. Kaplan,Sekar Kathiresan,Johannes Kettunen,Leena Kinnunen,Joshua W. Knowles,Ivana Kolcic,Inke R. Koenig,Seppo Koskinen,Peter Kovacs,Johanna Kuusisto,Peter Kraft,Kirsti Kvaløy,Jaana Laitinen,Olivier Lantieri,Chiara Lanzani,Lenore J. Launer,Cécile Lecoeur,Cécile Lecoeur,Terho Lehtimaeki,Guillaume Lettre,Guillaume Lettre,Jianjun Liu,Marja-Liisa Lokki,Mattias Lorentzon,Robert Luben,Barbara Ludwig,Paolo Manunta,Diana Marek,Michel Marre,Nicholas G. Martin,Wendy L. McArdle,Anne McCarthy,Barbara McKnight,Thomas Meitinger,Olle Melander,David Meyre,David Meyre,Kristian Midthjell,Grant W. Montgomery,Mario A. Morken,Andrew P. Morris,Rosanda Mulić,Julius S. Ngwa,Mari Nelis,Mari Nelis,Matt Neville,Dale R. Nyholt,Christopher J. O'Donnell,Stephen O'Rahilly,Ken K. Ong,Ben A. Oostra,Guillaume Paré,Alex N. Parker,Markus Perola,Irene Pichler,Kirsi H. Pietilaeinen,Carl G. P. Platou,Ozren Polasek,Anneli Pouta,Suzanne Rafelt,Olli T. Raitakari,Nigel W. Rayner,Martin Ridderstråle,Winfried Rief,Aimo Ruokonen,Neil Robertson,Peter Rzehak,Veikko Salomaa,Alan R. Sanders,Manjinder S. Sandhu,Manjinder S. Sandhu,Serena Sanna,Jouko Saramies,Markku J. Savolainen,Susann Scherag,Sabine Schipf,Stefan Schreiber,Heribert Schunkert,Kaisa Silander,Juha Sinisalo,David S. Siscovick,Jan Smit,Nicole Soranzo,Nicole Soranzo,Ulla Sovio,Jonathan Stephens,Jonathan Stephens,Ida Surakka,Amy J. Swift,Mari-Liis Tammesoo,Jean-Claude Tardif,Jean-Claude Tardif,Maris Teder-Laving,Tanya M. Teslovich,John R. Thompson,John R. Thompson,Brian Thomson,Anke Toenjes,Tiinamaija Tuomi,Joyce B. J. van Meurs,Gert-Jan B. van Ommen,Vincent Vatin,Vincent Vatin,Jorma S. A. Viikari,Jorma S. A. Viikari,Sophie Visvikis-Siest,Veronique Vitart,Carla I. G. Vogel,Benjamin F. Voight,Lindsay L. Waite,Henri Wallaschofski,G. Bragi Walters,Elisabeth Widen,Susanna Wiegand,Sarah H. Wild,Gonneke Willemsen,Daniel R. Witte,Jacqueline C. M. Witteman,Jianfeng Xu,Qunyuan Zhang,Lina Zgaga,Andreas Ziegler,Paavo Zitting,John Beilby,I. Sadaf Farooqi,Johannes Hebebrand,Heikki V. Huikuri,Alan James,Mika Kaehoenen,Douglas F. Levinson,Fabio Macciardi,Fabio Macciardi,Markku S. Nieminen,Claes Ohlsson,Lyle J. Palmer,Paul M. Ridker,Paul M. Ridker,Michael Stumvoll,Jacques S. Beckmann,Heiner Boeing,Eric Boerwinkle,Dorret I. Boomsma,Mark J. Caulfield,Stephen J. Chanock,Francis S. Collins,L. Adrienne Cupples,George Davey Smith,Jeanette Erdmann,Philippe Froguel,Philippe Froguel,Philippe Froguel,Henrik Greonberg,Ulf Gyllensten,Per Hall,Torben Hansen,Tamara B. Harris,Andrew T. Hattersley,Richard B. Hayes,Joachim Heinrich,Frank B. Hu,Frank B. Hu,Kristian Hveem,Thomas Illig,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Jaakko Kaprio,Fredrik Karpe,Kay-Tee Khaw,Lambertus A. Kiemeney,Heiko Krude,Markku Laakso,Debbie A Lawlor,Andres Metspalu,Patricia B. Munroe,Willem H. Ouwehand,Willem H. Ouwehand,Willem H. Ouwehand,Oluf Pedersen,Oluf Pedersen,Brenda W.J.H. Penninx,Brenda W.J.H. Penninx,Annette Peters,Peter P. Pramstaller,Thomas Quertermous,Thomas Reinehr,Aila Rissanen,Igor Rudan,Igor Rudan,Nilesh J. Samani,Peter Schwarz,Alan R. Shuldiner,Tim D. Spector,Jaakko Tuomilehto,Manuela Uda,André G. Uitterlinden,Timo T. Valle,Martin Wabitsch,Gerard Waeber,Nicholas J. Wareham,Hugh Watkins,James F. Wilson,Alan F. Wright,M. Carola Zillikens,Nilanjan Chatterjee,Steven A. McCarroll,Shaun Purcell,Eric E. Schadt,Peter M. Visscher,Themistocles L. Assimes,Ingrid B. Borecki,Panos Deloukas,Caroline S. Fox,Leif Groop,Talin Haritunians,David J. Hunter,David J. Hunter,Robert C. Kaplan,Karen L. Mohlke,Jeffrey R. O'Connell,Leena Peltonen,David Schlessinger,David P. Strachan,Cornelia M. van Duijn,H-Erich Wichmann,Timothy M. Frayling,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Gonçalo R. Abecasis,Inês Barroso,Inês Barroso,Michael Boehnke,Kari Stefansson,Kari Stefansson,Kari E. North,Mark I. McCarthy,Joel N. Hirschhorn,Erik Ingelsson,Ruth J. F. Loos +413 more
TL;DR: Genetic loci associated with body mass index map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor, which may provide new insights into human body weight regulation.
Journal ArticleDOI
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
Andre Franke,Dermot P.B. McGovern,Jeffrey C. Barrett,Kai Wang,Graham L. Radford-Smith,Tariq Ahmad,Charlie W. Lees,Tobias Balschun,James Lee,Rebecca L. Roberts,Carl A. Anderson,Joshua C. Bis,Suzanne Bumpstead,David Ellinghaus,Eleonora M. Festen,Michel Georges,Todd Green,Talin Haritunians,Luke Jostins,Anna Latiano,Christopher G. Mathew,Grant W. Montgomery,Natalie J. Prescott,Soumya Raychaudhuri,Jerome I. Rotter,Philip Schumm,Yashoda Sharma,Lisa A. Simms,Kent D. Taylor,David C. Whiteman,Cisca Wijmenga,Robert N. Baldassano,Murray L. Barclay,Theodore M. Bayless,Stephan Brand,Carsten Büning,Albert Cohen,Jean Frederick Colombel,Mario Cottone,Laura Stronati,Ted Denson,Martine De Vos,Renata D'Incà,Marla Dubinsky,Cathryn Edwards,Timothy H. Florin,Denis Franchimont,Richard B. Gearry,Jürgen Glas,Jürgen Glas,Jürgen Glas,André Van Gossum,Stephen L. Guthery,Jonas Halfvarson,Hein W. Verspaget,Jean-Pierre Hugot,Amir Karban,Debby Laukens,Ian C. Lawrance,Marc Lémann,Arie Levine,Cécile Libioulle,Edouard Louis,Craig Mowat,William G. Newman,Julián Panés,Anne M. Phillips,Deborah D. Proctor,Miguel Regueiro,Richard K Russell,Paul Rutgeerts,Jeremy D. Sanderson,Miquel Sans,Frank Seibold,A. Hillary Steinhart,Pieter C. F. Stokkers,Leif Törkvist,Gerd A. Kullak-Ublick,David C. Wilson,Thomas D. Walters,Stephan R. Targan,Steven R. Brant,John D. Rioux,Mauro D'Amato,Rinse K. Weersma,Subra Kugathasan,Anne M. Griffiths,John C. Mansfield,Severine Vermeire,Richard H. Duerr,Mark S. Silverberg,Jack Satsangi,Stefan Schreiber,Judy H. Cho,Vito Annese,Hakon Hakonarson,Mark J. Daly,Miles Parkes +97 more
TL;DR: A meta-analysis of six Crohn's disease genome-wide association studies and a series of in silico analyses highlighted particular genes within these loci implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP.
Journal ArticleDOI
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
Georg Ehret,Georg Ehret,Georg Ehret,Patricia B. Munroe,Kenneth Rice,Murielle Bochud,Andrew D. Johnson,Daniel I. Chasman,Albert V. Smith,Martin D. Tobin,Germaine C. Verwoert,Shih-Jen Hwang,Vasyl Pihur,Peter Vollenweider,Paul F. O'Reilly,Najaf Amin,Jennifer L. Bragg-Gresham,Alexander Teumer,Nicole L. Glazer,Lenore J. Launer,Jing Hua Zhao,Yurii S. Aulchenko,Simon Heath,Siim Sõber,Afshin Parsa,Jian'an Luan,Pankaj Arora,Abbas Dehghan,Feng Zhang,Gavin Lucas,Andrew A. Hicks,Anne U. Jackson,John F. Peden,Toshiko Tanaka,Sarah H. Wild,Igor Rudan,Igor Rudan,Wilmar Igl,Yuri Milaneschi,Alex Parker,Cristiano Fava,Cristiano Fava,John C. Chambers,John C. Chambers,Ervin R. Fox,Meena Kumari,Min Jin Go,Pim van der Harst,Wen Hong Linda Kao,Marketa Sjögren,D. G. Vinay,Myriam Alexander,Yasuharu Tabara,Sue Shaw-Hawkins,Peter H. Whincup,Yongmei Liu,Gang Shi,Johanna Kuusisto,Bamidele O. Tayo,Mark Seielstad,Mark Seielstad,Xueling Sim,Khanh-Dung H. Nguyen,Terho Lehtimäki,Giuseppe Matullo,Ying Wu,Tom R. Gaunt,N. Charlotte Onland-Moret,Mark E. Cooper,Carl G. P. Platou,Elin Org,Rebecca Hardy,Santosh Dahgam,Jutta Palmen,Veronique Vitart,Peter S. Braund,Peter S. Braund,Tatiana Kuznetsova,Cuno S.P.M. Uiterwaal,Adebowale Adeyemo,Walter Palmas,Harry Campbell,Barbara Ludwig,Maciej Tomaszewski,Maciej Tomaszewski,Ioanna Tzoulaki,Ioanna Tzoulaki,Nicholette D. Palmer,Thor Aspelund,Melissa Garcia,Yen Pei C. Chang,Jeffrey R. O'Connell,Nanette I. Steinle,Diederick E. Grobbee,Dan E. Arking,Sharon L.R. Kardia,Alanna C. Morrison,Dena G. Hernandez,Samer S. Najjar,Samer S. Najjar,Wendy L. McArdle,David Hadley,David Hadley,Morris J. Brown,John M. C. Connell,Aroon D. Hingorani,Ian N. M. Day,Debbie A Lawlor,John Beilby,Robert W. Lawrence,Robert Clarke,Jemma C. Hopewell,Halit Ongen,Albert W. Dreisbach,Yali Li,J. Hunter Young,Joshua C. Bis,Mika Kähönen,Jorma Viikari,Linda S. Adair,Nanette R. Lee,Ming-Huei Chen,Matthias Olden,Cristian Pattaro,Judith A. Hoffman Bolton,Anna Köttgen,Anna Köttgen,Sven Bergmann,Sven Bergmann,Vincent Mooser,Nish Chaturvedi,Timothy M. Frayling,Muhammad Islam,Tazeen H. Jafar,Jeanette Erdmann,Smita R. Kulkarni,Stefan R. Bornstein,Jürgen Grässler,Leif Groop,Benjamin F. Voight,Johannes Kettunen,Philip Howard,Andrew M. Taylor,Simonetta Guarrera,Fulvio Ricceri,Valur Emilsson,Andrew S. Plump,Inês Barroso,Inês Barroso,Kay-Tee Khaw,Alan B. Weder,Steven C. Hunt,Yan V. Sun,Richard N. Bergman,Francis S. Collins,Lori L. Bonnycastle,Laura J. Scott,Heather M. Stringham,Leena Peltonen,Markus Perola,Erkki Vartiainen,Stefan Martin Brand,Jan A. Staessen,Thomas J. Wang,Thomas J. Wang,Paul Burton,Paul Burton,María Soler Artigas,Yanbin Dong,Harold Snieder,Harold Snieder,Xiaoling Wang,Haidong Zhu,Kurt Lohman,Megan E. Rudock,Susan R. Heckbert,Susan R. Heckbert,Nicholas L. Smith,Nicholas L. Smith,Nicholas L. Smith,Kerri L. Wiggins,Ayo P. Doumatey,Daniel Shriner,Gudrun Veldre,Margus Viigimaa,Sanjay Kinra,Dorairaj Prabhakaran,Vikal Tripathy,Carl D. Langefeld,Annika Rosengren,Dag S. Thelle,Anna Maria Corsi,Andrew B. Singleton,Terrence Forrester,Gina Hilton,Colin A. McKenzie,Tunde Salako,Naoharu Iwai,Yoshikuni Kita,Toshio Ogihara,Takayoshi Ohkubo,Takayoshi Ohkubo,Tomonori Okamura,Hirotsugu Ueshima,Satoshi Umemura,Susana Eyheramendy,Thomas Meitinger,H.-Erich Wichmann,Yoon Shin Cho,Hyung Lae Kim,Jong-Young Lee,James Scott,Joban Sehmi,Joban Sehmi,Weihua Zhang,Bo Hedblad,Peter M. Nilsson,George Davey Smith,Andrew Wong,Narisu Narisu,Alena Stančáková,Leslie J. Raffel,Jie Yao,Sekar Kathiresan,Sekar Kathiresan,Christopher J. O'Donnell,Christopher J. O'Donnell,Stephen M. Schwartz,M. Arfan Ikram,W. T. Longstreth,Thomas H. Mosley,Sudha Seshadri,Nick Shrine,Louise V. Wain,Mario A. Morken,Amy J. Swift,Jaana Laitinen,Inga Prokopenko,Inga Prokopenko,Paavo Zitting,Jackie A. Cooper,Steve E. Humphries,John Danesh,Asif Rasheed,Anuj Goel,Anders Hamsten,Hugh Watkins,Stephan J. L. Bakker,Wiek H. van Gilst,C. S. Janipalli,K. Radha Mani,Chittaranjan S. Yajnik,Albert Hofman,Francesco U.S. Mattace-Raso,Ben A. Oostra,Ayse Demirkan,Aaron Isaacs,Fernando Rivadeneira,Edward G. Lakatta,Marco Orrù,Angelo Scuteri,Mika Ala-Korpela,Mika Ala-Korpela,Antti J. Kangas,Leo-Pekka Lyytikäinen,Pasi Soininen,Pasi Soininen,Taru Tukiainen,Taru Tukiainen,Taru Tukiainen,Peter Würtz,Peter Würtz,Peter Würtz,Rick Twee-HeeOng,Rick Twee-HeeOng,Marcus Dörr,Heyo K. Kroemer,Uwe Völker,Henry Völzke,Pilar Galan,Serge Hercberg,Mark Lathrop,Diana Zelenika,Panos Deloukas,Massimo Mangino,Tim D. Spector,Guangju Zhai,James F. Meschia,Mike A. Nalls,Pankaj Sharma,Janoš Terzić,M.V. Kranthi Kumar,Matthew Denniff,Ewa Zukowska-Szczechowska,Lynne E. Wagenknecht,F. Gerald R. Fowkes,Fadi J. Charchar,Peter Schwarz,Caroline Hayward,Xiuqing Guo,Charles N. Rotimi,Michiel L. Bots,Eva Brand,Nilesh J. Samani,Nilesh J. Samani,Ozren Polasek,Philippa J. Talmud,Fredrik Nyberg,Fredrik Nyberg,Diana Kuh,Maris Laan,Kristian Hveem,Lyle J. Palmer,Lyle J. Palmer,Yvonne T. van der Schouw,Juan P. Casas,Karen L. Mohlke,Paolo Vineis,Olli T. Raitakari,Santhi K. Ganesh,Tien Yin Wong,Tien Yin Wong,E. Shyong Tai,Richard S. Cooper,Markku Laakso,Dabeeru C. Rao,Tamara B. Harris,Richard W Morris,Anna F. Dominiczak,Mika Kivimäki,Michael Marmot,Tetsuro Miki,Danish Saleheen,Giriraj R. Chandak,Josef Coresh,Gerjan Navis,Veikko Salomaa,Bok Ghee Han,Xiaofeng Zhu,Jaspal S. Kooner,Jaspal S. Kooner,Olle Melander,Paul M. Ridker,Stefania Bandinelli,Ulf Gyllensten,Alan F. Wright,James F. Wilson,Luigi Ferrucci,Martin Farrall,Jaakko Tuomilehto,Peter P. Pramstaller,Roberto Elosua,Nicole Soranzo,Nicole Soranzo,Eric J.G. Sijbrands,David Altshuler,David Altshuler,Ruth J. F. Loos,Alan R. Shuldiner,Alan R. Shuldiner,Christian Gieger,Pierre Meneton,André G. Uitterlinden,Nicholas J. Wareham,Vilmundur Gudnason,Jerome I. Rotter,Rainer Rettig,Manuela Uda,David P. Strachan,Jacqueline C. M. Witteman,Anna-Liisa Hartikainen,Jacques S. Beckmann,Eric Boerwinkle,Ramachandran S. Vasan,Ramachandran S. Vasan,Michael Boehnke,Martin G. Larson,Martin G. Larson,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Bruce M. Psaty,Bruce M. Psaty,Gonçalo R. Abecasis,Aravinda Chakravarti,Paul Elliott,Cornelia M. van Duijn,Christopher Newton-Cheh,Christopher Newton-Cheh,Daniel Levy,Mark J. Caulfield,Toby Johnson +391 more
TL;DR: A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function, and these findings suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Journal ArticleDOI
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,Sailaja Vedantam,Soumya Raychaudhuri,Soumya Raychaudhuri,Teresa Ferreira,Andrew R. Wood,Robert J. Weyant,Ayellet V. Segrè,Ayellet V. Segrè,Elizabeth K. Speliotes,Elizabeth K. Speliotes,Eleanor Wheeler,Nicole Soranzo,Nicole Soranzo,Ju-Hyun Park,Jian Yang,Daniel F. Gudbjartsson,Nancy L. Heard-Costa,Joshua C. Randall,Lu Qi,Albert V. Smith,Reedik Mägi,Tomi Pastinen,Liming Liang,Iris M. Heid,Jian'an Luan,Gudmar Thorleifsson,Thomas W. Winkler,Michael E. Goddard,Michael E. Goddard,Ken Sin Lo,Cameron D. Palmer,Cameron D. Palmer,Tsegaselassie Workalemahu,Yurii S. Aulchenko,Åsa Johansson,Åsa Johansson,M. Carola Zillikens,Mary F. Feitosa,Tõnu Esko,Tõnu Esko,Toby Johnson,Toby Johnson,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,Zoltán Kutalik,Keri L. Monda,Ozren Polasek,Michael Preuss,Nigel W. Rayner,Neil R. Robertson,Valgerdur Steinthorsdottir,Jonathan Tyrer,Benjamin F. Voight,Benjamin F. Voight,Fredrik Wiklund,Jianfeng Xu,Jing Hua Zhao,Dale R. Nyholt,Niina Pellikka,Niina Pellikka,Markus Perola,Markus Perola,John Perry,Ida Surakka,Ida Surakka,Mari Liis Tammesoo,Elizabeth L. Altmaier,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,Elin Grundberg,Ke Hao,M. Juhani Junttila,Lee M. Kaplan,Johannes Kettunen,Johannes Kettunen,Inke R. König,Tony Kwan,Robert W. Lawrence,Douglas F. Levinson,Mattias Lorentzon,Barbara McKnight,Andrew P. Morris,Martina Müller,Julius S. Ngwa,Shaun Purcell,Shaun Purcell,Suzanne Rafelt,Rany M. Salem,Rany M. Salem,Erika Salvi,Serena Sanna,Jianxin Shi,Ulla Sovio,John R. Thompson,John R. Thompson,Michael C. Turchin,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,Jennie Hui,Wilmar Igl,Thomas Illig,Antti Jula,Eero Kajantie,Tuomas O. Kilpeläinen,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,Anneli Pouta,Martin Ridderstråle,Jerome I. Rotter,Jennifer G. Sambrook,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,Mari Nelis,Marjolein J. Peters,Samuli Ripatti,Samuli Ripatti,Joyce B. J. van Meurs,Katja K.H. Aben,Kristin G. Ardlie,Jacques S. Beckmann,John Beilby,John Beilby,Richard N. Bergman,Sven Bergmann,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,Carlos Iribarren,Mika Kähönen,Jaakko Kaprio,Jaakko Kaprio,Sekar Kathiresan,Sekar Kathiresan,Sekar Kathiresan,Lambertus A. Kiemeney,Thomas D. Kocher,Lenore J. Launer,Terho Lehtimäki,Olle Melander,Thomas H. Mosley,Arthur W. Musk,Arthur W. Musk,Markku S. Nieminen,Christopher J. O'Donnell,Christopher J. O'Donnell,Claes Ohlsson,Ben A. Oostra,Lyle J. Palmer,Lyle J. Palmer,Olli T. Raitakari,Paul M. Ridker,John D. Rioux,Aila Rissanen,Carlo Rivolta,Heribert Schunkert,Alan R. Shuldiner,Alan R. Shuldiner,David S. Siscovick,Michael Stumvoll,Anke Tönjes,Jaakko Tuomilehto,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,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-Riitta Järvelin,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Vincent Mooser,Patricia B. Munroe,Willem H. Ouwehand,Willem H. Ouwehand,Willem H. Ouwehand,Brenda W.J.H. Penninx,Brenda W.J.H. Penninx,Peter P. Pramstaller,Thomas Quertermous,Igor Rudan,Igor Rudan,Nilesh J. Samani,Nilesh J. Samani,Tim D. Spector,Henry Völzke,Hugh Watkins,James F. Wilson,Leif Groop,Talin Haritunians,Frank B. Hu,Robert C. Kaplan,Andres Metspalu,Andres Metspalu,Kari E. North,David Schlessinger,Nicholas J. Wareham,David J. Hunter,Jeffrey R. O'Connell,David P. Strachan,H.-Erich Wichmann,Ingrid B. Borecki,Cornelia M. van Duijn,Eric E. Schadt,Eric E. Schadt,Unnur Thorsteinsdottir,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,Kari Stefansson,Timothy M. Frayling,Joel N. Hirschhorn,Joel N. Hirschhorn +344 more
TL;DR: It is shown that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, and indicates that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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.
References
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Finding the missing heritability of complex diseases
Teri A. Manolio,Francis S. Collins,Nancy J. Cox,David Goldstein,Lucia A. Hindorff,David J. Hunter,Mark I. McCarthy,Erin M. Ramos,Lon R. Cardon,Aravinda Chakravarti,Judy H. Cho,Alan E. Guttmacher,Augustine Kong,Leonid Kruglyak,Leonid Kruglyak,Elaine R. Mardis,Charles N. Rotimi,Montgomery Slatkin,David Valle,Alice S. Whittemore,Michael Boehnke,Andrew G. Clark,Evan E. Eichler,Greg Gibson,Jonathan L. Haines,Trudy F. C. Mackay,Steven A. McCarroll,Peter M. Visscher +27 more
TL;DR: This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
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Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland
Paul Lichtenstein,Niels V. Holm,Pia K. Verkasalo,Anastasia Iliadou,Jaakko Kaprio,Jaakko Kaprio,Markku Koskenvuo,Markku Koskenvuo,Eero Pukkala,Axel Skytthe,Kari Hemminki +10 more
TL;DR: Inherited genetic factors make a minor contribution to susceptibility to most types of neoplasms, which indicates that the environment has the principal role in causing sporadic cancer.
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Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
Jeffrey C. Barrett,Sarah Hansoul,Dan L. Nicolae,Judy H. Cho,Richard H. Duerr,John D. Rioux,John D. Rioux,Steven R. Brant,Mark S. Silverberg,Kent D. Taylor,M. Michael Barmada,Alain Bitton,Themistocles Dassopoulos,Lisa W. Datta,Todd Green,Anne M. Griffiths,Emily O. Kistner,Michael T. Murtha,Miguel Regueiro,Jerome I. Rotter,L. Philip Schumm,A. Hillary Steinhart,Stephan R. Targan,Ramnik J. Xavier,Cécile Libioulle,Cynthia Sandor,Mark Lathrop,Jacques Belaiche,Olivier Dewit,Ivo Gut,Simon Heath,Debby Laukens,Myriam Mni,Paul Rutgeerts,André Van Gossum,Diana Zelenika,Denis Franchimont,Jean-Pierre Hugot,Martine De Vos,Severine Vermeire,Edouard Louis,Lon R. Cardon,Carl A. Anderson,Hazel E. Drummond,Elaine R. Nimmo,Tariq Ahmad,Natalie J. Prescott,Clive M. Onnie,Sheila A. Fisher,Jonathan Marchini,Jilur Ghori,Suzannah Bumpstead,Rhian Gwilliam,Mark Tremelling,Panos Deloukas,John C. Mansfield,Derek P. Jewell,Jack Satsangi,Christopher G. Mathew,Miles Parkes,Michel Georges,Mark J. Daly,Mark J. Daly +62 more
TL;DR: The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1, which offer promise for informed therapeutic development.
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Genome-wide association study identifies novel breast cancer susceptibility loci
Douglas F. Easton,Karen A. Pooley,Alison M. Dunning,Paul D.P. Pharoah,Deborah J. Thompson,Dennis G. Ballinger,Jeffery P. Struewing,Jonathan J. Morrison,Helen I. Field,Robert Luben,Nicholas J. Wareham,Shahana Ahmed,Catherine S. Healey,Richard Bowman,Kerstin B. Meyer,Christopher A. Haiman,Laurence K. Kolonel,Brian E. Henderson,Loic Le Marchand,Paul Brennan,Suleeporn Sangrajrang,Valerie Gaborieau,Fabrice Odefrey,Chen-Yang Shen,Pei-Ei Wu,Hui-Chun Wang,Diana Eccles,D. Gareth Evans,Julian Peto,Olivia Fletcher,Nichola Johnson,Sheila Seal,Michael R. Stratton,Nazneen Rahman,Georgia Chenevix-Trench,Georgia Chenevix-Trench,Stig E. Bojesen,Børge G. Nordestgaard,C K Axelsson,Montserrat Garcia-Closas,Louise A. Brinton,Stephen J. Chanock,Jolanta Lissowska,Beata Peplonska,Heli Nevanlinna,Rainer Fagerholm,H Eerola,Daehee Kang,Keun-Young Yoo,Dong-Young Noh,Sei Hyun Ahn,David J. Hunter,Susan E. Hankinson,David G. Cox,Per Hall,Sara Wedrén,Jianjun Liu,Yen-Ling Low,Natalia Bogdanova,Peter Schu¨rmann,Do¨rk Do¨rk,Rob A. E. M. Tollenaar,Catharina E. Jacobi,Peter Devilee,Jan G. M. Klijn,Alice J. Sigurdson,Michele M. Doody,Bruce H. Alexander,Jinghui Zhang,Angela Cox,Ian W. Brock,Gordon MacPherson,Malcolm W.R. Reed,Fergus J. Couch,Ellen L. Goode,Janet E. Olson,Hanne Meijers-Heijboer,Hanne Meijers-Heijboer,Ans M.W. van den Ouweland,André G. Uitterlinden,Fernando Rivadeneira,Roger L. Milne,Gloria Ribas,Anna González-Neira,Javier Benitez,John L. Hopper,Margaret R. E. McCredie,Margaret R. E. McCredie,Margaret R. E. McCredie,Melissa C. Southey,Melissa C. Southey,Graham G. Giles,Chris Schroen,Christina Justenhoven,Christina Justenhoven,Hiltrud Brauch,Hiltrud Brauch,Ute Hamann,Yon-Dschun Ko,Amanda B. Spurdle,Jonathan Beesley,Xiaoqing Chen,_ kConFab,Arto Mannermaa,Veli-Matti Kosma,Vesa Kataja,Jaana M. Hartikainen,Nicholas E. Day,David Cox,Bruce A.J. Ponder +109 more
TL;DR: To identify further susceptibility alleles, a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls was conducted, followed by a third stage in which 30 single nucleotide polymorphisms were tested for confirmation.
Journal ArticleDOI
Methods for Detecting Associations with Rare Variants for Common Diseases : Application to Analysis of Sequence Data
Bingshan Li,Suzanne M. Leal +1 more
TL;DR: It is shown that the collapsing method, which involves collapsing genotypes across variants and applying a univariate test, is powerful for analyzing rare variants, whereas multivariate analysis is robust against inclusion of noncausal variants.
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