Genomic control for association studies.
Bernie Devlin,Kathryn Roeder +1 more
Reads0
Chats0
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
More filters
Journal ArticleDOI
Regional admixture mapping and structured association testing: conceptual unification and an extensible general linear model.
David T. Redden,Jasmin Divers,Laura Vaughan,Hemant K. Tiwari,T. Mark Beasley,Jose R. Fernandez,Robert P. Kimberly,Rui Feng,Miguel A. Padilla,Nianjun Liu,Michael B. Miller,David B. Allison +11 more
TL;DR: This work provides a conceptual framework in which both RAM and SAT are special cases of a more general linear model, and clarifies which variables are sufficient to condition upon in order to prevent spurious associations and provides a simple closed form “semiparametric” method of evaluating the reliability of individual admixture estimates.
Journal ArticleDOI
Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity.
Anubha Mahajan,Aylin R. Rodan,Thu H. Le,Kyle J. Gaulton,Jeffrey Haessler,Adrienne M. Stilp,Yoichiro Kamatani,Gu Zhu,Tamar Sofer,Sanjana Puri,Jeffrey N. Schellinger,Pei-Lun Chu,Sylvia Cechova,Natalie van Zuydam,Johan Ärnlöv,Johan Ärnlöv,Michael F. Flessner,Vilmantas Giedraitis,Andrew C. Heath,Michiaki Kubo,Anders Larsson,Cecilia M. Lindgren,Cecilia M. Lindgren,Pamela A. F. Madden,Grant W. Montgomery,George J. Papanicolaou,Alexander P. Reiner,Johan Sundström,Timothy A. Thornton,Lars Lind,Erik Ingelsson,Erik Ingelsson,Jianwen Cai,Nicholas G. Martin,Charles Kooperberg,Koichi Matsuda,John Whitfield,Yukinori Okada,Cathy C. Laurie,Andrew P. Morris,Andrew P. Morris,Nora Franceschini +41 more
TL;DR: The utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect is demonstrated and salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans is suggested.
Journal ArticleDOI
Variant Association Tools for Quality Control and Analysis of Large-Scale Sequence and Genotyping Array Data
Gao Wang,Bo Peng,Suzanne M. Leal +2 more
TL;DR: Highlights of VAT include variant-site and call-level quality control (QC), summary statistics, phenotype- and genotype-based sample selection, variant annotation, selection of variants for association analysis, and a collection of rare-variant association methods for analyzing qualitative and quantitative traits.
Journal ArticleDOI
Genetic determinants of the inflammatory response.
TL;DR: Naturally occurring genetic variants in important inflammatory mediators such as TNF-α and TLR4 appear to alter inflammatory responses in numerous experimental and a few clinical models of inflammation, but inconsistencies exist in the literature regarding the association between these genetic variants and disease susceptibility and prognosis.
Journal ArticleDOI
The eMERGE genotype set of 83,717 subjects imputed to ~40 million variants genome wide and association with the herpes zoster medical record phenotype.
Ian B. Stanaway,Taryn O. Hall,Elisabeth A. Rosenthal,Melody R. Palmer,Vivek Naranbhai,Vivek Naranbhai,Rachel Knevel,Bahram Namjou-Khales,Robert J. Carroll,Krzysztof Kiryluk,Adam S. Gordon,Jodell E. Linder,Kayla Marie Howell,Brandy Mapes,Frederick T.J. Lin,Yoonjung Yoonie Joo,M. Geoffrey Hayes,Ali G. Gharavi,Sarah A. Pendergrass,Marylyn D. Ritchie,Mariza de Andrade,Damien C. Croteau-Chonka,Soumya Raychaudhuri,Scott T. Weiss,Matthew S. Lebo,Sami S. Amr,David Carrell,Eric B. Larson,Christopher G. Chute,Laura J. Rasmussen-Torvik,Megan J Roy-Puckelwartz,Patrick M. A. Sleiman,Hakon Hakonarson,Rongling Li,Elizabeth W. Karlson,Josh F. Peterson,Iftikhar J. Kullo,Rex L. Chisholm,Joshua C. Denny,Gail P. Jarvik,David R. Crosslin +40 more
TL;DR: The quality control and filtering steps used in the generation of this data set and suggest generalizable quality thresholds for imputation and phenotype association studies are described are described and suggested.
References
More filters
Journal ArticleDOI
Stastical Decision Theory and Bayesian Analysis.
Malay Ghosh,James O. Berger +1 more
Book
Statistical Decision Theory and Bayesian Analysis
TL;DR: An overview of statistical decision theory, which emphasizes the use and application of the philosophical ideas and mathematical structure of decision theory.
Journal ArticleDOI
The Future of Genetic Studies of Complex Human Diseases
TL;DR: The identification of the genetic basis of complex human diseases such as schizophrenia and diabetes has proven difficult as mentioned in this paper, and Risch and Merikangas proposed that they can best accomplish this goal by combining the power of the human genome project with association studies.
Journal ArticleDOI
An Introduction to Population Genetics Theory
James F. Crow,Motoo Kimura +1 more
TL;DR: An introduction to population genetics theory, An introduction to Population Genetics Theory, Population Genetics theory, Population genetics theory as discussed by the authors, Population genetics, population genetics, and population genetics theories, Population Genetic Theory
Book
An introduction to population genetics theory
James F. Crow,Motoo Kimura +1 more
TL;DR: An introduction to population genetics theory, An introduction to Population Genetics theory, and more.
Related Papers (5)
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Inference of population structure using multilocus genotype data
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