Journal ArticleDOI
Association study designs for complex diseases
Lon R. Cardon,John I. Bell +1 more
Reads0
Chats0
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
More filters
Journal ArticleDOI
Variants in exon 11 of MEF2A gene and coronary artery disease: evidence from a case-control study, systematic review, and meta-analysis.
TL;DR: It is concluded that the rare 21-bp deletion might have a more compelling effect on CAD than the common (CAG)n polymorphism, and MEF2A genetic variant might be a rare but specific cause of CAD/MI.
Journal ArticleDOI
Suggestive evidence for association of two potassium channel genes with different idiopathic generalised epilepsy syndromes.
Barry A. Chioza,Abena Osei-Lah,Hazel Wilkie,Lina Nashef,Lina Nashef,D McCormick,Philip Asherson,Andrew Makoff +7 more
TL;DR: One SNP was associated with epilepsy with generalised tonic clonic seizures only, as was an SNP approximately 56 kb distant in the closely linked nicotinic acetylcholine gene CHRNA4, suggesting that if they are not true associations they have independently occurred by chance.
Journal ArticleDOI
The TLR4 +896 polymorphism is not associated with lipopolysaccharide hypo-responsiveness in leukocytes
TL;DR: It is shown that human carriers of this polymorphism show no deficit in LPS induced peripheral blood mononuclear cell (PBMC) mitogen-activated protein kinase (MAPK) activity, no reduction in sensitivity to endotoxin, and variable differences in whole-blood inflammatory cytokine production.
Journal ArticleDOI
The epidemiologic approach to pharmacogenomics.
TL;DR: It is suggested that there may be opportunities to exploit samples from trials already completed to investigate possible gene-drug interactions, and to consider the use of the case-only design nested within randomized controlled trials as a possible means of reducing genotyping costs when dichotomous outcomes are being investigated.
Journal ArticleDOI
Genetics of Temporal Lobe Epilepsy: A Review
Annick Salzmann,Alain Malafosse +1 more
TL;DR: Genetic findings for TLE are listed from the initial segregation analysis to the most recent results published in May 2011 to determine which gene variant combination plays a definitive role in the aetiology of TLE.
References
More filters
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.
Journal ArticleDOI
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes
Marcy E. MacDonald,Christine Ambrose,Mabel P. Duyao,Richard H. Myers,Carol Lin,Lakshmi Srinidhi,Glenn Barnes,Sherryl A.M. Taylor,Marianne James,Nicolet Groot,Heather MacFarlane,Barbara Jenkins,Mary Anne Anderson,Nancy S. Wexler,James F. Gusella,Gillian P. Bates,Sarah Baxendale,Holger Hummerich,Susan F. Kirby,Mike North,S. Youngman,Richard Mott,Günther Zehetner,Zdenek Sedlacek,Annemarie Poustka,Anna-Maria Frischauf,Hans Lehrach,Alan Buckler,Deanna M. Church,Lynn Doucette-Stamm,Michael Conlon O'Donovan,Laura Riba-Ramirez,Manish A. Shah,Vincent P. Stanton,Scott A. Strobel,Karen M. Draths,Jennifer L. Wales,Peter B. Dervan,David E. Housman,Michael R. Altherr,Rita Shiang,Leslie M. Thompson,Thomas J. Fielder,John J. Wasmuth,Danilo A. Tagle,John Valdes,Lawrence W. Elmer,Marc W. Allard,Lucio H. Castilla,Manju Swaroop,Kris Blanchard,Francis S. Collins,Russell G. Snell,Tracey Holloway,Kathleen Gillespie,Nicole A. Datson,Duncan Shaw,Peter S. Harper +57 more
TL;DR: In this article, the authors used haplotype analysis of linkage disequilibrium to spotlight a small segment of 4p16.3 as the likely location of the defect, which is expanded and unstable on HD chromosomes.
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.
Related Papers (5)
The Structure of Haplotype Blocks in the Human Genome
Stacey Gabriel,Stephen F. Schaffner,Huy Nguyen,Jamie Moore,Jessica Roy,Brendan Blumenstiel,John M. Higgins,Matthew DeFelice,Amy L. Lochner,Maura Faggart,Shau Neen Liu-Cordero,Charles N. Rotimi,Adebowale Adeyemo,Richard S. Cooper,Ryk Ward,Eric S. Lander,Mark J. Daly,David Altshuler,David Altshuler +18 more