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
Citations
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Journal ArticleDOI
Localized breakdown in linkage disequilibrium does not always predict sperm crossover hot spots in the human MHC class II region.
TL;DR: Sperm crossover analysis of one region revealed a novel localized hot spot similar in intensity and morphology to most other MHC hot spots, which highlights the complexity of LD patterns and the importance of experimentally verifying crossover hot spots.
Journal ArticleDOI
Identifying the susceptibility genes for coronary artery disease: from hyperbole through doubt to cautious optimism
Anders Hamsten,Per Eriksson +1 more
TL;DR: Evidence has been obtained that multiple rare alleles with fairly strong phenotypic effects may contribute to the genetic heritability of CAD, in addition to common variants with a modest impact on risk.
Journal ArticleDOI
Admixture-matched case-control study: a practical approach for genetic association studies in admixed populations.
Hui Ju Tsai,Hui Ju Tsai,Jennifer Kho,Jennifer Kho,Nishat Shaikh,Nishat Shaikh,Shweta Choudhry,Shweta Choudhry,Mariam Naqvi,Mariam Naqvi,Daniel Navarro,Daniel Navarro,Henry Matallana,Henry Matallana,Richard A. Castro,Richard A. Castro,Craig M. Lilly,H. George Watson,Kelley Meade,Michael A. LeNoir,Shannon Thyne,Elad Ziv,Esteban G. Burchard,Esteban G. Burchard +23 more
TL;DR: Admixture-matched case-control strategies can efficiently control population stratification confounding in admixed populations, and it is demonstrated population stratifying was not a confounder in the authors' genetic association.
MonographDOI
Chronic Pain Epidemiology
TL;DR: This book discusses chronic pain as a topic for epidemiology and public health, the genetic epidemiology of pain, and the potential for prevention in populations at risk of chronic pain.
Journal ArticleDOI
Developing a quantitative measure of alcohol consumption for genomic studies on prospective cohorts.
Arpana Agrawal,Julia D. Grant,Andrew K. Littlefield,Mary Waldron,Michele L. Pergadia,Michael T. Lynskey,Pamela A. F. Madden,Alexandre A. Todorov,Timothy J. Trull,Timothy J. Trull,Kathleen K. Bucholz,Richard D. Todd,Kenneth J. Sher,Kenneth J. Sher,Andrew C. Heath +14 more
TL;DR: Quantitative measures ofcohol consumption with the favorable attributes of measurement invariance, construct validity, and moderate heritability can greatly enhance future gene-mapping efforts, supplementing information afforded by conventional diagnostic measures of alcohol abuse/dependence.
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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