Genomic control for association studies.
Bernie Devlin,Kathryn Roeder +1 more
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TLDR
The performance of the genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders.Abstract:
A dense set of single nucleotide polymorphisms (SNP) covering the genome and an efficient method to assess SNP genotypes are expected to be available in the near future. An outstanding question is how to use these technologies efficiently to identify genes affecting liability to complex disorders. To achieve this goal, we propose a statistical method that has several optimal properties: It can be used with case control data and yet, like family-based designs, controls for population heterogeneity; it is insensitive to the usual violations of model assumptions, such as cases failing to be strictly independent; and, by using Bayesian outlier methods, it circumvents the need for Bonferroni correction for multiple tests, leading to better performance in many settings while still constraining risk for false positives. The performance of our genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders.read more
Citations
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Journal ArticleDOI
Assessing the impact of population stratification on genetic association studies.
Matthew L. Freedman,Matthew L. Freedman,David Reich,David Reich,Kathryn L. Penney,Kathryn L. Penney,Gavin J. McDonald,Gavin J. McDonald,Andre A. Mignault,Nick Patterson,Stacey Gabriel,Eric J. Topol,Jordan W. Smoller,Carlos N. Pato,Carlos N. Pato,Michele T. Pato,Michele T. Pato,Tracey L. Petryshen,Laurence N. Kolonel,Eric S. Lander,Eric S. Lander,Pamela Sklar,Pamela Sklar,Brian E. Henderson,Joel N. Hirschhorn,Joel N. Hirschhorn,David Altshuler +26 more
TL;DR: The results suggest that modest amounts of stratification can exist even in well designed studies and that assessments based on a few dozen markers lack power to rule out moderate levels of stratisation that could cause false positive associations in studies designed to detect modest genetic risk factors.
Journal ArticleDOI
GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment
Cornelius A. Rietveld,Sarah E. Medland,Jaime Derringer,Jian Yang,Tõnu Esko,Nicolas W. Martin,Nicolas W. Martin,Harm-Jan Westra,Konstantin Shakhbazov,Abdel Abdellaoui,Arpana Agrawal,Eva Albrecht,Behrooz Z. Alizadeh,Najaf Amin,John Barnard,Sebastian E. Baumeister,Kelly S. Benke,Lawrence F. Bielak,Jeffrey A. Boatman,Patricia A. Boyle,Gail Davies,Christiaan de Leeuw,Niina Eklund,Niina Eklund,Daniel S. Evans,Rudolf Ferhmann,Krista Fischer,Christian Gieger,Håkon K. Gjessing,Sara Hägg,Sara Hägg,Jennifer R. Harris,Caroline Hayward,Christina Holzapfel,Carla A. Ibrahim-Verbaas,Erik Ingelsson,Erik Ingelsson,Bo Jacobsson,Bo Jacobsson,Peter K. Joshi,Astanand Jugessur,Marika Kaakinen,Stavroula Kanoni,Juha Karjalainen,Ivana Kolcic,Kati Kristiansson,Kati Kristiansson,Zoltán Kutalik,Zoltán Kutalik,Jari Lahti,Sang Hong Lee,Peng Lin,Penelope A. Lind,Yongmei Liu,Kurt Lohman,Marisa Loitfelder,George McMahon,Pedro Marques Vidal,Osorio Meirelles,Lili Milani,Ronny Myhre,Marja-Liisa Nuotio,Marja-Liisa Nuotio,Christopher Oldmeadow,Katja Petrovic,Wouter J. Peyrot,Ozren Polasek,Lydia Quaye,Eva Reinmaa,John P. Rice,Thais S. Rizzi,Helena Schmidt,Reinhold Schmidt,Albert V. Smith,Jennifer A. Smith,Toshiko Tanaka,Antonio Terracciano,Antonio Terracciano,Matthijs J. H. M. van der Loos,Veronique Vitart,Henry Völzke,Jürgen Wellmann,Lei Yu,Wei Zhao,Jüri Allik,John Attia,Stefania Bandinelli,François Bastardot,Jonathan P. Beauchamp,David A. Bennett,Klaus Berger,Laura J. Bierut,Dorret I. Boomsma,Ute Bültmann,Harry Campbell,Christopher F. Chabris,Lynn Cherkas,Mina K. Chung,Francesco Cucca,Francesco Cucca,Mariza de Andrade,Philip L. De Jager,Jan-Emmanuel De Neve,Jan-Emmanuel De Neve,Ian J. Deary,George Dedoussis,Panos Deloukas,Maria Dimitriou,Guoný Eiríksdóttir,Martin F. Elderson,Johan G. Eriksson,David M. Evans,Jessica D. Faul,Luigi Ferrucci,Melissa E. Garcia,Henrik Grönberg,Vilmundur Guonason,Per Hall,Juliette Harris,Tamara B. Harris,Nicholas D. Hastie,Andrew C. Heath,Dena G. Hernandez,Wolfgang Hoffmann,Adriaan Hofman,Rolf Holle,Elizabeth G. Holliday,Jouke-Jan Hottenga,William G. Iacono,Thomas Illig,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Mika Kähönen,Jaakko Kaprio,Jaakko Kaprio,Robert M. Kirkpatrick,Matthew Kowgier,Antti Latvala,Antti Latvala,Lenore J. Launer,Debbie A Lawlor,Terho Lehtimäki,Jingmei Li,Paul Lichtenstein,Peter Lichtner,David C. Liewald,Pamela A. F. Madden,Patrik K. E. Magnusson,Tomi E. Mäkinen,Marco Masala,Matt McGue,Andres Metspalu,Andreas Mielck,Michael B. Miller,Grant W. Montgomery,Sutapa Mukherjee,Sutapa Mukherjee,Dale R. Nyholt,Ben A. Oostra,Lyle J. Palmer,Aarno Palotie,Aarno Palotie,Brenda W.J.H. Penninx,Markus Perola,Markus Perola,Markus Perola,Patricia A. Peyser,Martin Preisig,Katri Räikkönen,Olli T. Raitakari,Anu Realo,Susan M. Ring,Samuli Ripatti,Samuli Ripatti,Samuli Ripatti,Fernando Rivadeneira,Igor Rudan,Aldo Rustichini,Veikko Salomaa,Antti-Pekka Sarin,David Schlessinger,Rodney J. Scott,Harold Snieder,Beate St Pourcain,John M. Starr,Jae Hoon Sul,Ida Surakka,Ida Surakka,Rauli Svento,Alexander Teumer,Henning Tiemeier,Frank J. A. van Rooij,David R. Van Wagoner,Erkki Vartiainen,Jorma Viikari,Peter Vollenweider,Judith M. Vonk,Gérard Waeber,David R. Weir,H.-Erich Wichmann,Elisabeth Widen,Gonneke Willemsen,James F. Wilson,Alan F. Wright,Dalton Conley,George Davey-Smith,Lude Franke,Patrick J. F. Groenen,Albert Hofman,Magnus Johannesson,Sharon L.R. Kardia,Robert F. Krueger,David Laibson,Nicholas G. Martin,Michelle N. Meyer,Michelle N. Meyer,Danielle Posthuma,Danielle Posthuma,Roy Thurik,Nicholas J. Timpson,André G. Uitterlinden,Cornelia M. van Duijn,Cornelia M. van Duijn,Peter M. Visscher,Peter M. Visscher,Daniel J. Benjamin,David Cesarini,David Cesarini,David Cesarini,Philipp Koellinger +230 more
TL;DR: In this article, a genome-wide association study of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490 individuals, and three independent SNPs are genome wide significant (rs9320913, rs11584700, rs4851266).
Journal ArticleDOI
Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity
Lam C. Tsoi,Sarah L. Spain,Sarah L. Spain,Jo Knight,Eva Ellinghaus,Eva Ellinghaus,Philip E. Stuart,Francesca Capon,Jun Ding,Yanming Li,Trilokraj Tejasvi,Johann E. Gudjonsson,Hyun Min Kang,Michael H. Allen,Ross McManus,Giuseppe Novelli,Lena Samuelsson,Joost Schalkwijk,Mona Ståhle,A. David Burden,Catherine H. Smith,Michael J. Cork,Xavier Estivill,Anne M. Bowcock,Gerald G. Krueger,Wolfgang Weger,Jane Worthington,Rachid Tazi-Ahnini,Frank O. Nestle,Adrian Hayday,Per Hoffmann,Juliane Winkelmann,Cisca Wijmenga,Cordelia Langford,Sarah Edkins,Robert Andrews,Hannah Blackburn,Amy Strange,Gavin Band,Richard D. Pearson,Damjan Vukcevic,Chris C. A. Spencer,Panos Deloukas,Ulrich Mrowietz,Stefan Schreiber,Stephan Weidinger,Sulev Kõks,Külli Kingo,Tõnu Esko,Andres Metspalu,Henry W. Lim,John J. Voorhees,Michael Weichenthal,H.-Erich Wichmann,Vinod Chandran,Cheryl F. Rosen,Proton Rahman,Dafna D. Gladman,Christopher E.M. Griffiths,André Reis,Juha Kere,Juha Kere,Rajan P. Nnair,Andre Franke,Jonathan Nn Barker,Ggoncalo R. Abecasis,James Tt Eelder,Richard Ttrembath,Richard Ttrembath,Kristina Callis Duffin,Cindy Helms,David E. Goldgar,Yun Li,Justin Paschall,Justin Paschall,Mary J. Malloy,Mary J. Malloy,Clive R. Pullinger,Clive R. Pullinger,John P. Kane,John P. Kane,Jennifer M. Gardner,Amy Perlmutter,Andrew Miner,Bing Jian Feng,Ravi Hiremagalore,Robert W. Ike,Enno Christophers,Tilo Henseler,Andreas Ruether,Steven J. Schrodi,Sampath Prahalad,Sampath Prahalad,Stephen L. Guthery,Stephen L. Guthery,Judith Fischer,Wilson Liao,Pui Kwok,Alan Menter,G. Mark Lathrop,Carol Wise,Ann B. Begovich,Alexandros Onoufriadis,Michael E. Weale,Angelika Hofer,Wolfgang Salmhofer,Peter Wolf,Kati Kainu,Ulpu Saarialho-Kere,Sari Suomela,Petra Badorf,Ulrike Hüffmeier,Werner Kurrat,Wolfgang Küster,Jesús Lascorz,Rotraut Mössner,Funda Schürmeier-Horst,Markward Ständer,Heiko Traupe,Judith G.M. Bergboer,Martin den Heijer,Martin den Heijer,Peter C.M. van de Kerkhof,Patrick L.J.M. Zeeuwen,L. Barnes,Linda E. Campbell,Caitriona Cusack,Ciara Coleman,Judith Conroy,Sean Ennis,Oliver FitzGerald,Phil Gallagher,Alan D. Irvine,Brian Kirby,Trevor Markham,W.H. Irwin McLean,Joe McPartlin,Sarah Rogers,Anthony W. Ryan,Agnieszka Zawirska,Emiliano Giardina,Tiziana Lepre,Carlo Perricone,Gemma Martin-Ezquerra,Ramon M. Pujol,Eva Riveira-Muñoz,Annica Inerot,Åsa Torinsson Naluai,Lotus Mallbris,Katarina Wolk,Joyce Leman,Anne Barton,Richard B. Warren,Helen S. Young,Isis Ricaño-Ponce,Gosia Trynka,Fawnda Pellett,Andrew Henschel,Marin Aurand,Bruce F. Bebo,Christian Gieger,Thomas Illig,Susanne Moebus,Karl-Heinz Jöckel,Raimund Erbel,Peter Donnelly,Peter Donnelly,Leena Peltonen,Jenefer M. Blackwell,Elvira Bramon,Elvira Bramon,Matthew A. Brown,Juan P. Casas,Aiden Corvin,Nicholas Craddock,Audrey Duncanson,Janusz Jankowski,Hugh S. Markus,Christopher G. Mathew,Mark I. McCarthy,Colin N. A. Palmer,Robert Plomin,Anna Rautanen,Stephen J. Sawcer,Nilesh J. Samani,Ananth C. Viswanathan,Nicholas W. Wood,Céline Bellenguez,Colin Freeman,Garrett Hellenthal,Eleni Giannoulatou,Matti Pirinen,Zhan Su,Sarah E. Hunt,Rhian Gwilliam,Suzannah Bumpstead,Serge Dronov,Matthew W. Gillman,Emma Gray,Naomi Hammond,Alagurevathi Jayakumar,O. T. McCann,Jennifer Liddle,M. Perez,Simon C. Potter,Radhi Ravindrarajah,Michelle Ricketts,Matthew Waller,Paul A. Weston,Sara Widaa,Pamela Whittaker,Rajan P. Neir,Jonathan Barker,Gonçalo R. Abecasis,James T. Elder,Richard C. Trembath +215 more
TL;DR: A meta-analysis of genome-wide association studies and independent data sets genotyped on the Immunochip identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals, and identified five independent signals within previously known loci.
A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1
A. Strange,Francesca Capon,C. C. A. Spencer,Joanne Knight,Michael E. Weale,Michael H. Allen,Anne Barton,Céline Bellenguez,Judith G.M. Bergboer,J. M. BlackweL,Elvira Bramon,Suzannah Bumpstead,Juan P. Casas,Michael J. Cork,Aiden Corvin,Panagiotis Deloukas,Alexander T. Dilthey,Audrey Duncanson,Sarah Edkins,X. EstiviL,Oliver FitzGerald,C. FrEman,Emiliano Giardina,Emma Gray,Angelika Hofer,Ulrike Hüffmeier,Sarah E. Hunt,Alan D. Irvine,Janusz Jankowski,Brian Kirby,Cordelia Langford,Jesús Lascorz,Joyce Leman,Stephen Leslie,L. MaLbris,Hugh S. Markus,Christopher G. Mathew,Whi McLean,Ross McManus,R. MöSner,Loukas Moutsianas,Åsa Torinsson Naluai,Frank O. Nestle,G. NoveLi,Alexandros Onoufriadis,Colin N. A. Palmer,Carlo Perricone,Matti Pirinen,Robert Plomin,S. C. PoTer,Ramon M. Pujol,Anna Rautanen,Eva Riveira-Muñoz,Anthony W. Ryan,Wolfgang Salmhofer,L. SamuelSon,Stephen Sawcer,Joost Schalkwijk,Catherine H. Smith,Mona Ståhle,Zhan Su,Rachid Tazi-Ahnini,Heiko Traupe,Ananth C. Viswanathan,Richard B. Warren,Wolfgang Weger,Katarina Wolk,N. Wod,Jane Worthington,Helen S. Young,Patrick L.J.M. Zeeuwen,Adrian Hayday,A D Burden,Christopher E.M. Griffiths,Juha Kere,André Reis,Gil McVean,David M. Evans,Matthew A. Brown,J. Barker,Leena Peltonen,P. Donely,Richard C. Trembath +82 more
TL;DR: In this article, a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls was conducted.
Journal ArticleDOI
Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer.
Simon N. Stacey,Andrei Manolescu,Patrick Sulem,Thorunn Rafnar,Julius Gudmundsson,Sigurjon A. Gudjonsson,Gisli Masson,Margret Jakobsdottir,Steinunn Thorlacius,Agnar Helgason,Katja K.H. Aben,Luc J Strobbe,Marjo T Albers-Akkers,Dorine W. Swinkels,Brian E. Henderson,Laurence N. Kolonel,Loic Le Marchand,Esther Millastre,Raquel Andrés,Javier Godino,Maria D. Garcia-Prats,E. Polo,Alejandro Tres,Magali Mouy,Jona Saemundsdottir,Valgerdur M Backman,Larus J. Gudmundsson,Kristleifur Kristjansson,Jon Thor Bergthorsson,Jelena Kostic,Michael L. Frigge,Frank Geller,Daniel F. Gudbjartsson,Helgi Sigurdsson,Thora Jonsdottir,Jon Hrafnkelsson,Jakob Johannsson,Thorarinn Sveinsson,Gardar Myrdal,Hlynur Niels Grimsson,Thorvaldur Jonsson,Susanna von Holst,Barbro Werelius,Sara Margolin,Annika Lindblom,Jose I. Mayordomo,Christopher A. Haiman,Lambertus A. Kiemeney,Oskar T. Johannsson,Jeffrey R. Gulcher,Unnur Thorsteinsdottir,Augustine Kong,Kari Stefansson +52 more
TL;DR: Two SNPs consistently associated with breast cancer are identified: rs3803662 is near the 5′ end of TNRC9 , a high mobility group chromatin–associated protein whose expression is implicated in breast cancer metastasis to bone.
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