Linked Life Data

17094266

Source:http://linkedlifedata.com/resource/pubmed/id/17094266

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2006-11-10
pubmed:abstractText
Despite recent advances, very-high-throughput (VHT) technologies capable of genotyping hundreds of thousands of SNPs in individual samples remain prohibitively expensive for the large studies necessary to screen substantial sections of the genome for variants with modest effects on disease risk. This paper presents a two-stage strategy, where a portion of available samples are genotyped with VHT technology, and a small number of the most promising variants are genotyped with standard high-throughput techniques in the remaining samples as an independent replication study. The sample sizes in the first and second stages and the corresponding significance levels are chosen to limit False Positive Report Probability (FPRP), while maximizing the number of Expected True Positives (ETPs). (The FPRP is the conditional probability that a marker is not truly associated with disease, given the a significant test for disease-marker association.) For a fixed budget, the two-stage strategy has greater power (a larger number of ETPs) than the single-stage strategy (where all subjects are genotyped using expensive VHT technology). Furthermore, concentrating on the FPRP leads to considerable savings relative to strategies designed to control the family-wise error (e.g. Bonferonni correction). The FPRP and number of ETPs can also accommodate researchers' prior beliefs about the number of causal loci and the magnitude of their effects. The expected number of false positives does not change if the true number and effects of causal loci differs from the specified prior (although the false discovery rate will vary), thus limiting the absolute amount of resources spent chasing "false leads."
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:issn
1793-5091
pubmed:author
pubmed:issnType
Print
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
523-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Efficient two-stage genome-wide association designs based on false positive report probabilities.
pubmed:affiliation
Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02112, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural