Journal ArticleDOI
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
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Book ChapterDOI
Linkage disequilibrium mapping for complex disease genes.
TL;DR: This chapter lays out some background information about gene mapping for human complex traits and covers issues such as study design, high-throughput genotyping technologies, statistical analysis, and others.
Journal ArticleDOI
La pharmacorésistance des épilepsies partielles : épidémiologie, mécanismes, pharmacogénétique, perspectives thérapeutiques
TL;DR: It is established that 20–30% of epilepsies are not controlled by antiepileptic drugs and the potential role of multidrug transporters as well as their genetic control and the altered sensitivity of neuronal drug receptors has gained growing attention.
Journal ArticleDOI
Power considerations for λ inflation factor in meta-analyses of genome-wide association studies.
TL;DR: The results provide a quick but detailed index for power considerations of future meta-analyses of GWAS that enables a more flexible design from early steps based on the number of studies accumulated in different groups and the λ values observed in the single studies.
Journal ArticleDOI
An investigation of polymorphisms in innate and adaptive immune response genes in canine leishmaniosis.
Francesca Soutter,Laia Solano-Gallego,Charalampos Attipa,Luigi Gradoni,Eleonora Fiorentino,Valentina Foglia Manzillo,Gaetano Oliva,Séverine Tasker,Christopher R Helps,Brian Catchpole +9 more
TL;DR: The aim of this study was to examine polymorphisms in innate and adaptive immune response genes, to determine whether any of these were associated with susceptibility or resistance to L. infantum infection.
Journal ArticleDOI
A Generic Research Paradigm for Identification and Validation of Early Molecular Diagnostics and New Therapeutics in Common Disorders
TL;DR: New insights into biomarker detection utilizing the most current genomic technologies available are discussed and a generic paradigm for the validation of such molecular diagnostics as well as new treatment modalities for complex and increasingly common diseases are presented.
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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