PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
Reads0
Chats0
TLDR
This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.Abstract:
Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.read more
Citations
More filters
Journal ArticleDOI
New loci associated with kidney function and chronic kidney disease
Anna Köttgen,Anna Köttgen,Cristian Pattaro,Carsten A. Böger,Christian Fuchsberger,Matthias Olden,Nicole L. Glazer,Afshin Parsa,Xiaoyi Gao,Qiong Yang,Albert V. Smith,Jeffrey R. O'Connel,Man Li,Helena Schmidt,Toshiko Tanaka,Toshiko Tanaka,Aaron Isaacs,Shamika Ketkar,Shih-Jen Hwang,Andrew D. Johnson,Abbas Dehghan,Alexander Teumer,Guillaume Paré,Elizabeth J. Atkinson,Tanja Zeller,Kurt Lohman,Marilyn C. Cornelis,Nicole Probst-Hensch,Nicole Probst-Hensch,Florian Kronenberg,Anke Tönjes,Caroline Hayward,Thor Aspelund,Gudny Eiriksdottir,Lenore J. Launer,Tamara B. Harris,Evadnie Rampersaud,Braxton D. Mitchel,Dan E. Arking,Eric Boerwinkle,Maksim Struchalin,Margherita Cavalieri,Andrew B. Singleton,Francesco Giallauria,Jeffrey Metter,Ian H. de Boer,Talin Haritunians,Thomas Lumley,David S. Siscovick,Bruce M. Psaty,M. CarolaZillikens,Ben A. Oostra,Mary F. Feitosa,Michael A. Province,Mariza de Andrade,Stephen T. Turner,Arne Schillert,Andreas Ziegler,Philipp S. Wild,Renate B. Schnabel,Sandra Wilde,Thomas Münzel,Tennille S. Leak,Thomas Illig,Norman Klopp,Christa Meisinger,H.-Erich Wichmann,Wolfgang Koenig,Lina Zgaga,Tatijana Zemunik,Ivana Kolcic,Cosetta Minelli,Frank B. Hu,Åsa Johansson,Wilmar Igl,Ghazal Zaboli,Sarah H. Wild,Alan F. Wright,Harry Campbell,David Ellinghaus,Stefan Schreiber,Yurii S. Aulchenko,Janine F. Felix,Fernando Rivadeneira,André G. Uitterlinden,Albert Hofman,Medea Imboden,Medea Imboden,Dorothea Nitsch,Anita Brandstätter,Barbara Kollerits,Lyudmyla Kedenko,Reedik Mägi,Michael Stumvoll,Peter Kovacs,Mladen Boban,Susan Campbell,Karlhans Endlich,Henry Völzke,Heyo K. Kroemer,Matthias Nauck,Uwe Völker,Ozren Polasek,Veronique Vitart,Sunita Badola,Alex Parker,Paul M. Ridker,Sharon L.R. Kardia,Stefan Blankenberg,Yongmei Liu,Gary C. Curhan,Andre Franke,Thierry Rochat,Bernhard Paulweber,Inga Prokopenko,Wei Wang,Wei Wang,Vilmundur Gudnason,Alan R. Shuldine,Josef Coresh,Reinhold E. Schmidt,Luigi Ferrucci,Michael G. Shlipak,Cornelia M. van Duijn,Ingrid B. Borecki,Bernhard K. Krämer,Igor Rudan,Ulf Gyllensten,James F. Wilson,Jacqueline C. M. Witteman,Peter P. Pramstaller,Rainer Rettig,Nicholas D. Hastie,Daniel I. Chasman,Wen Hong L. Kao,Iris M. Heid,Caroline S. Fox,Caroline S. Fox +137 more
TL;DR: The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry to identify new susceptibility loci for reduced renal function as estimated by serum creatinine, serum cystatin c and CKD.
Journal ArticleDOI
A versatile gene-based test for genome-wide association studies
Jimmy Z. Liu,Allan F. McRae,Dale R. Nyholt,Sarah E. Medland,Naomi R. Wray,Kevin M. Brown,Nicholas K. Hayward,Grant W. Montgomery,Peter M. Visscher,Nicholas G. Martin,Stuart MacGregor +10 more
TL;DR: This work derived a versatile gene-based test for genome-wide association studies (GWAS) that has the potential to identify novel associated genes; provide a basis for selecting SNPs for replication; and be directly used in network (pathway) approaches that require per-gene association test statistics.
Journal ArticleDOI
A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
Vesela Gateva,Johanna K. Sandling,Geoff Hom,Kimberly E. Taylor,Sharon A. Chung,Xin Sun,Ward Ortmann,Roman Kosoy,Ricardo C. Ferreira,Gunnel Nordmark,Iva Gunnarsson,Elisabet Svenungsson,Leonid Padyukov,Gunnar Sturfelt,Andreas Jönsen,Anders A. Bengtsson,Solbritt Rantapää-Dahlqvist,Emily C. Baechler,Elizabeth E. Brown,Graciela S. Alarcón,Jeffrey C. Edberg,Rosalind Ramsey-Goldman,Gerald McGwin,John D. Reveille,Luis M. Vilá,Robert P. Kimberly,Susan Manzi,Michelle Petri,Annette Lee,Peter K. Gregersen,Michael F. Seldin,Lars Rönnblom,Lindsey A. Criswell,Ann-Christine Syvänen,Timothy W. Behrens,Robert R. Graham +35 more
TL;DR: The results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
Journal ArticleDOI
Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta
Ana Griciuc,Alberto Serrano-Pozo,Antonio R. Parrado,Andrea N. Lesinski,Caroline Asselin,Kristina Mullin,Basavaraj Hooli,Se Hoon Choi,Bradley T. Hyman,Rudolph E. Tanzi +9 more
TL;DR: The minor allele of the CD33 SNP rs3865444, which confers protection against AD, was associated with reductions in both CD33 expression and insoluble amyloid beta 42 levels in AD brain and CD33 inhibition could represent a novel therapy for AD.
Journal ArticleDOI
Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
Robert A. Scott,Vasiliki Lagou,Ryan P. Welch,Eleanor Wheeler,May E. Montasser,Jian'an Luan,Reedik Mägi,Rona J. Strawbridge,Emil Rehnberg,Stefan Gustafsson,Stavroula Kanoni,Laura J. Rasmussen-Torvik,Loic Yengo,Cécile Lecoeur,Dmitry Shungin,Serena Sanna,Carlo Sidore,Paul C. D. Johnson,J. Wouter Jukema,Toby Johnson,Anubha Mahajan,Niek Verweij,Gudmar Thorleifsson,Jouke-Jan Hottenga,Sonia Shah,Albert V. Smith,Bengt Sennblad,Christian Gieger,Perttu Salo,Markus Perola,Nicholas J. Timpson,David M. Evans,Beate St Pourcain,Ying Wu,Jeanette S. Andrews,Jennie Hui,Lawrence F. Bielak,Wei Zhao,Momoko Horikoshi,Pau Navarro,Aaron Isaacs,Jeffrey R. O'Connell,Kathleen Stirrups,Veronique Vitart,Caroline Hayward,Tõnu Esko,Evelin Mihailov,Ross M. Fraser,Tove Fall,Benjamin F. Voight,Soumya Raychaudhuri,Han Chen,Cecilia M. Lindgren,Andrew P. Morris,Nigel W. Rayner,Neil Robertson,Denis Rybin,Ching-Ti Liu,Jacques S. Beckmann,Sara M. Willems,Peter S. Chines,Anne U. Jackson,Hyun Min Kang,Heather M. Stringham,Kijoung Song,Toshiko Tanaka,John F. Peden,Anuj Goel,Andrew A. Hicks,Ping An,Martina Müller-Nurasyid,Anders Franco-Cereceda,Lasse Folkersen,Letizia Marullo,Hanneke Jansen,Albertine J. Oldehinkel,Marcel Bruinenberg,James S. Pankow,Kari E. North,Nita G. Forouhi,Ruth J. F. Loos,Sarah Edkins,Tibor V. Varga,Göran Hallmans,Heikki Oksa,Mulas Antonella,Ramaiah Nagaraja,Stella Trompet,Ian Ford,Stephan J. L. Bakker,Augustine Kong,Meena Kumari,Bruna Gigante,Christian Herder,Patricia B. Munroe,Mark J. Caulfield,Jula Antti,Massimo Mangino,Kerrin S. Small,Iva Miljkovic,Yongmei Liu,Mustafa Atalay,Wieland Kiess,Alan James,Fernando Rivadeneira,André G. Uitterlinden,Colin N. A. Palmer,Alex S. F. Doney,Gonneke Willemsen,Johannes H. Smit,Susan Campbell,Ozren Polasek,Lori L. Bonnycastle,Serge Hercberg,Maria Dimitriou,Jennifer L. Bolton,Gerard R Fowkes,Peter Kovacs,Jaana Lindström,Tatijana Zemunik,Stefania Bandinelli,Sarah H. Wild,Hanneke Basart,Wolfgang Rathmann,Harald Grallert,Winfried Maerz,Marcus E. Kleber,Bernhard O. Boehm,Annette Peters,Peter P. Pramstaller,Michael A. Province,Ingrid B. Borecki,Nicholas D. Hastie,Igor Rudan,Harry Campbell,Hugh Watkins,Martin Farrall,Michael Stumvoll,Luigi Ferrucci,Dawn M. Waterworth,Richard N. Bergman,Francis S. Collins,Jaakko Tuomilehto,Richard M. Watanabe,Eco J. C. de Geus,Brenda W.J.H. Penninx,Albert Hofman,Ben A. Oostra,Bruce M. Psaty,Peter Vollenweider,James F. Wilson,Alan F. Wright,G. Kees Hovingh,Andres Metspalu,Matti Uusitupa,Patrik K. E. Magnusson,Kirsten Ohm Kyvik,Jaakko Kaprio,Jackie F. Price,George Dedoussis,Panos Deloukas,Pierre Meneton,Lars Lind,Michael Boehnke,Alan R. Shuldiner,Cornelia M. van Duijn,Andrew D. Morris,Anke Toenjes,Patricia A. Peyser,John Beilby,John Beilby,Antje Körner,Johanna Kuusisto,Markku Laakso,Stefan R. Bornstein,Peter Schwarz,Timo A. Lakka,Rainer Rauramaa,Linda S. Adair,George Davey Smith,Tim D. Spector,Thomas Illig,Ulf de Faire,Anders Hamsten,Vilmundur Gudnason,Mika Kivimäki,Aroon D. Hingorani,Sirkka Keinänen-Kiukaanniemi,T. Saaristo,Dorret I. Boomsma,Kari Stefansson,Pim van der Harst,Josée Dupuis,Nancy L. Pedersen,Naveed Sattar,Tamara B. Harris,Francesco Cucca,Samuli Ripatti,Veikko Salomaa,Karen L. Mohlke,Beverley Balkau,Philippe Froguel,Anneli Pouta,Marjo-Riitta Järvelin,Nicholas J. Wareham,Nabila Bouatia-Naji,Nabila Bouatia-Naji,Nabila Bouatia-Naji,Mark I. McCarthy,Paul W. Franks,James B. Meigs,Tanya M. Teslovich,Jose C. Florez,Claudia Langenberg,Erik Ingelsson,Inga Prokopenko,Inês Barroso +216 more
TL;DR: Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations and further functional analysis of these newly discovered loci will further improve the understanding of glycemic control.
References
More filters
Journal ArticleDOI
Controlling the false discovery rate: a practical and powerful approach to multiple testing
Yoav Benjamini,Yosef Hochberg +1 more
TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
Journal ArticleDOI
Inference of population structure using multilocus genotype data
TL;DR: Pritch et al. as discussed by the authors proposed a model-based clustering method for using multilocus genotype data to infer population structure and assign individuals to populations, which can be applied to most of the commonly used genetic markers, provided that they are not closely linked.
Book
Statistical methods for rates and proportions
TL;DR: In this paper, the basic theory of Maximum Likelihood Estimation (MLE) is used to detect a difference between two different proportions of a given proportion in a single proportion.
Journal ArticleDOI
Haploview: analysis and visualization of LD and haplotype maps
TL;DR: Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface.
Journal ArticleDOI
Categorical Data Analysis
TL;DR: In this article, categorical data analysis was used for categorical classification of categorical categorical datasets.Categorical Data Analysis, categorical Data analysis, CDA, CPDA, CDSA