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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
A genome-wide scan and HCRTR2 candidate gene analysis in a European cluster headache cohort
L Baumber,Christina Sjöstrand,M. Leone,H. Harty,Gennaro Bussone,Jan Hillert,Richard C. Trembath,Michael Bjørn Russell +7 more
TL;DR: Cluster headache is a complex genetic disorder, with possible phenotypic and genetic heterogeneity compounding attempts at gene identification, and potential linkage was identified at four possible disease loci in Danish kindreds, yet no single chromosome location generated a lod or NPL score of recognized significance.
Journal ArticleDOI
Nonreplication in Genetic Studies of Complex Diseases—Lessons Learned From Studies of Osteoporosis and Tentative Remedies
Hui Shen,Hui Shen,Yong Jun Liu,Pengyuan Liu,Robert R. Recker,Hong-Wen Deng,Hong-Wen Deng,Hong-Wen Deng +7 more
TL;DR: Using osteoporosis as an example, major potential factors for the nonreplication results are addressed and some potential remedies are proposed.
Journal ArticleDOI
The Complex Genetic Architecture of Drosophila Life Span
Jeff Leips,Trudy F. C. Mackay +1 more
TL;DR: All of the QTL mapping data for Drosophila life span is summarized, the additive allelic effects and dominance of QTL were highly sex-specific, and future prospects for disentangling the genetic and environmental influences on this trait are outlined.
Journal ArticleDOI
Performance analysis of novel methods for detecting epistasis.
TL;DR: A comparison study of epistasis detection methods through applying related software packages on datasets, and AntEpiSeeker and BOOST are recommended as the efficient and effective methods.
Journal ArticleDOI
Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence
TL;DR: Findings provide the first evidence for the involvement of DDC in the susceptibility to ND and, further, reveal the racial specificity of its impact.
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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