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Association study designs for complex diseases
Lon R. Cardon,John I. Bell +1 more
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TLDR
With the discovery of massive numbers of genetic markers and the development of better tools for genotyping, association studies will inevitably proliferate and now is the time to consider critically the design of such studies to avoid the mistakes of the past and to maximize their potential to identify new components of disease.Abstract:
Assessing the association between DNA variants and disease has been used widely to identify regions of the genome and candidate genes that contribute to disease. However, there are numerous examples of associations that cannot be replicated, which has led to skepticism about the utility of the approach for common conditions. With the discovery of massive numbers of genetic markers and the development of better tools for genotyping, association studies will inevitably proliferate. Now is the time to consider critically the design of such studies, to avoid the mistakes of the past and to maximize their potential to identify new components of disease.read more
Citations
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Journal ArticleDOI
Bayesian approach to discovering pathogenic SNPs in conserved protein domains.
Zhaohui Cai,Eric F. Tsung,Voichita D. Marinescu,Marco F. Ramoni,Marco F. Ramoni,Alberto Riva,Isaac S. Kohane,Isaac S. Kohane +7 more
TL;DR: A novel algorithm to predict pathogenic single amino acid changes, either nonsynonymous SNPs (nsSNPs) or missense mutations, in conserved protein domains is developed using a Bayesian framework.
Journal ArticleDOI
Consistency of HLA associations between two independent measles vaccine cohorts: a replication study.
Inna G. Ovsyannikova,V. Shane Pankratz,Robert A. Vierkant,Robert M. Jacobson,Gregory A. Poland +4 more
TL;DR: This study emphasizes the importance of replicating HLA associations with measles vaccine-induced humoral and cellular immune responses and increases confidence in the results.
Journal ArticleDOI
Ubiquilin 1 polymorphisms are not associated with late-onset Alzheimer's disease
Scott Smemo,Petra Nowotny,Anthony L. Hinrichs,John S. K. Kauwe,Sara Cherny,Katherine Erickson,Amanda J. Myers,Mona Kaleem,Lauren Marlowe,Alison M. Gibson,Paul Hollingworth,Michael Conlon O'Donovan,Christopher Morris,Peter Holmans,Simon Lovestone,John C. Morris,Leon J. Thal,Yonghong Li,Andrew Grupe,John Hardy,Michael John Owen,Julie Williams,Alison Goate +22 more
TL;DR: Genotyping an intronic polymorphism affecting alternative splicing of exon 8 of ubiquilin 1 (UBQLN1) found no evidence that this single nucleotide polymorphism, or any of six others tested in UBQLN 1, increases risk for LOAD.
Journal ArticleDOI
Adrenergic-Receptor Polymorphisms and Heart Failure
Roger J. Hajjar,Calum A. MacRae +1 more
TL;DR: Congestive heart failure is the eventual outcome of diverse myocardial insults, including postischemic remodeling, primary cardiomyopathies, and infections.
Journal ArticleDOI
Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans
Bae Y,Chanmi Park,Jeong Woo Han,Hong Yj,Song Hh,Shin Es,Lee Je,Han Bg,Yangsoo Jang,Dong-Jik Shin,Sungjoo Kim Yoon +10 more
TL;DR: A significant interaction between the GNB3 825T and the ACE D alleles may contribute to the predisposing effect for the development of EH in Koreans.
References
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Journal Article
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
Manish A. Shah,Nicole A. Datson,Lakshmi Srinidhi,Vincent P. Stanton,Marcy E. MacDonald,Marc W. Allard,S. Youngman,Anna-Maria Frischauf,Richard Mott,KM Draths,Günther Zehetner,C. O’Donovan,Thomas J. Fielder,Bruce G. Jenkins,Manju Swaroop,Sherryl A.M. Taylor,Lynn Doucette-Stamm,Heather MacFarlane,Scott A. Strobel,H. E. McFarlane,Alan Buckler,Nicolet Groot,Holger Hummerich,Deanna M. Church,M. A. Anderson,Marianne James,Glenn Barnes,M. Christine,Francis S. Collins,Mabel P. Duyao,Peter B. Dervan,Gillian P. Bates,T Holloway,Peter S. Harper,TW Mcdonald,M North,K Blanchard,John J. Wasmuth,D. Shaw,Hans Lehrach,Danilo A. Tagle,Annemarie Poustka,David E. Housman,T. Huntington,Zdenek Sedlacek,Laura Riba,Susan F. Kirby,Carol Lin,Richard H. Myers,Leslie M. Thompson,Russell G. Snell,Michael Conlon O'Donovan,K Gillespie,Rita Shiang,Nancy S. Wexler,Christine Ambrose,J. F. Gusella,Sarah Baxendale,N. Groat,John Valdes +59 more
TL;DR: The Huntington's disease mutation involves an unstable DNA segment, similar to those described in fragile X syndrome, spino-bulbar muscular atrophy, and myotonic dystrophy, acting in the context of a novel 4p16.3 gene to produce a dominant phenotype.
Journal ArticleDOI
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
John R. Riordan,Johanna M. Rommens,Batsheva Kerem,Noa Alon,Richard Rozmahel,Zbyszko Grzelczak,Julian Zielenski,Si Lok,Natasa Plavsic,Jia Ling Chou,Mitchell L. Drumm,Michael C. Iannuzzi,Francis S. Collins,Lap-Chee Tsui +13 more
TL;DR: A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
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