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
Exome sequencing and the genetic basis of complex traits
Adam Kiezun,Kiran V. Garimella,Ron Do,Ron Do,Nathan O. Stitziel,Nathan O. Stitziel,Benjamin M. Neale,Benjamin M. Neale,Paul J. McLaren,Paul J. McLaren,Namrata Gupta,Pamela Sklar,Patrick F. Sullivan,Jennifer L. Moran,Christina M. Hultman,Paul Lichtenstein,Patrik K. E. Magnusson,Thomas Lehner,Yin Yao Shugart,Alkes L. Price,Alkes L. Price,Paul I.W. de Bakker,Paul I.W. de Bakker,Paul I.W. de Bakker,Shaun Purcell,Shamil R. Sunyaev,Shamil R. Sunyaev +26 more
TL;DR: Exome sequencing methods and their applications in studies to identify the genetic basis of human complex traits are presented and include analyses of the whole-exome sequences of 438 individuals from across several studies.
Journal ArticleDOI
Genome-wide association study of PR interval
Arne Pfeufer,Charlotte van Noord,Kristin D. Marciante,Dan E. Arking,Martin G. Larson,Martin G. Larson,Albert V. Smith,Kirill V. Tarasov,Martina Müller,Nona Sotoodehnia,Moritz F. Sinner,Germaine C. Verwoert,Man Li,W. H. Linda Kao,Anna Köttgen,Josef Coresh,Joshua C. Bis,Bruce M. Psaty,Bruce M. Psaty,Kenneth Rice,Jerome I. Rotter,Fernando Rivadeneira,Albert Hofman,Jan A. Kors,Bruno H. Stricker,André G. Uitterlinden,Cornelia M. van Duijn,Britt M. Beckmann,Wiebke Sauter,Christian Gieger,Steven A. Lubitz,Christopher Newton-Cheh,Thomas J. Wang,Thomas J. Wang,Jared W. Magnani,Renate B. Schnabel,Renate B. Schnabel,Mina K. Chung,John Barnard,Jonathan D. Smith,David R. Van Wagoner,Ramachandran S. Vasan,Ramachandran S. Vasan,Thor Aspelund,Gudny Eiriksdottir,Tamara B. Harris,Lenore J. Launer,Samer S. Najjar,Edward G. Lakatta,David Schlessinger,Manuela Uda,Gonçalo R. Abecasis,Bertram Müller-Myhsok,Georg Ehret,Eric Boerwinkle,Aravinda Chakravarti,Elsayed Z. Soliman,Kathryn L. Lunetta,Siegfried Perz,H.-Erich Wichmann,Thomas Meitinger,Daniel Levy,Vilmundur Gudnason,Patrick T. Ellinor,Serena Sanna,Stefan Kääb,Jacqueline C.M. Witteman,Alvaro Alonso,Emelia J. Benjamin,Emelia J. Benjamin,Susan R. Heckbert +70 more
TL;DR: A meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.
Journal ArticleDOI
Common variants at ten loci influence QT interval duration in the QTGEN Study.
Christopher Newton-Cheh,Christopher Newton-Cheh,Mark Eijgelsheim,Kenneth Rice,Paul I.W. de Bakker,Paul I.W. de Bakker,Xiaoyan Yin,Karol Estrada,Joshua C. Bis,Kristin D. Marciante,Fernando Rivadeneira,Peter A. Noseworthy,Nona Sotoodehnia,Nicholas L. Smith,Nicholas L. Smith,Jerome I. Rotter,Jan A. Kors,Jacqueline C.M. Witteman,Albert Hofman,Susan R. Heckbert,Susan R. Heckbert,Christopher J. O'Donnell,Christopher J. O'Donnell,André G. Uitterlinden,Bruce M. Psaty,Thomas Lumley,Martin G. Larson,Bruno H. Stricker +27 more
TL;DR: A meta-analysis of three genome-wide association studies in 13,685 individuals of European ancestry offers insights into myocardial repolarization and suggests candidate genes that could predispose to sudden cardiac death and drug-induced arrhythmias.
Journal ArticleDOI
Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo
Patrick F. Sullivan,E.J.C. de Geus,Gonneke Willemsen,Michael R. James,Jan Smit,T. Zandbelt,Volker Arolt,Bernhard T. Baune,D. H. R. Blackwood,Sven Cichon,William L. Coventry,Katharina Domschke,Anne Farmer,Maurizio Fava,S.D. Gordon,Qianchuan He,A. C. Heath,Peter Heutink,Florian Holsboer,Witte J.G. Hoogendijk,Jouke-Jan Hottenga,Yi Hu,Martin A. Kohli,Danyu Lin,Susanne Lucae,Donald J. MacIntyre,Wolfgang Maier,Kevin A. McGhee,Peter McGuffin,Grant W. Montgomery,Walter J. Muir,Willem A. Nolen,Markus M. Nöthen,Roy H. Perlis,K. Pirlo,Danielle Posthuma,Marcella Rietschel,Patrizia Rizzu,Alexandra Schosser,August B. Smit,Jordan W. Smoller,Jung-Ying Tzeng,R. van Dyck,Matthijs Verhage,Frans G. Zitman,N. G. Martin,Naomi R. Wray,Dorret I. Boomsma,B.W.J.H. Penninx +48 more
TL;DR: A genome-wide association study of single nucleotide polymorphisms genotyped in 1738 MDD cases and 1802 controls selected to be at low liability for MDD found 11 signals localized to a 167 kb region overlapping the gene piccolo, whose protein product localizes to the cytomatrix of the presynaptic active zone and is important in monoaminergic neurotransmission in the brain.
Journal ArticleDOI
A common variant of HMGA2 is associated with adult and childhood height in the general population
Michael N. Weedon,Guillaume Lettre,Guillaume Lettre,Rachel M. Freathy,Cecilia M. Lindgren,Cecilia M. Lindgren,Benjamin F. Voight,Benjamin F. Voight,John R. B. Perry,Katherine S. Elliott,Rachel Hackett,Candace Guiducci,Beverley M. Shields,Eleftheria Zeggini,Hana Lango,Valeriya Lyssenko,Valeriya Lyssenko,Nicholas J. Timpson,Nicholas J. Timpson,Noël P. Burtt,Nigel W. Rayner,Richa Saxena,Richa Saxena,Kristin Ardlie,Jonathan H Tobias,Andy R Ness,Susan M. Ring,Colin N. A. Palmer,Andrew D. Morris,Leena Peltonen,Leena Peltonen,Veikko Salomaa,George Davey Smith,Leif Groop,Leif Groop,Andrew T. Hattersley,Mark I. McCarthy,Mark I. McCarthy,Joel N. Hirschhorn,Joel N. Hirschhorn,Joel N. Hirschhorn,Timothy M. Frayling +41 more
TL;DR: There are few examples of common genetic variants reproducibly associated with human quantitativetraits; these results represent, to the authors' knowledge, the first consistently replicated association with adult and childhood height.
References
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