ArticleAmerican journal of human genetics2001
The power to detect linkage disequilibrium with quantitative traits in selected samples.
Article in American journal of human genetics, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- A unified framework for detecting rare variant quantitative trait associations in pedigree and unrelated individuals via sequence data.Human heredity · 2012Article
- Common variants show predicted polygenic effects on height in the tails of the distribution, except in extremely short individuals.PLoS genetics · 2011Article
- Identification of genes for bone mineral density variation by computational disease gene identification strategy.Journal of bone and mineral metabolism · 2011Article
- A simple bias correction in linear regression for quantitative trait association under two-tail extreme selection.Behavior genetics · 2011Article
- Bivariate association analysis in selected samples: application to a GWAS of two bone mineral density phenotypes in males with high or low BMD.European journal of human genetics : EJHG · 2011Article
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3 authors.
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Abstract
Results from power studies for linkage detection have led to many ongoing and planned collections of phenotypically extreme nuclear families. Given the great expense of collecting these families and the imminent availability of a dense diallelic marker map, the families are likely to be used in allelic-association as well as linkage studies. However, optimal selection strategies for linkage may not be equally powerful for association. We examine the power to detect linkage disequilibrium for quantitative traits after phenotypic selection. The results encompass six selection strategies that are in widespread use, including single selection (two designs), affected sib pairs, concordant and discordant pairs, and the extreme-concordant and -discordant design. Selection of sibships on the basis of one extreme proband with high or low trait scores provides as much power as discordant sib pairs but requires the screening and phenotyping of substantially fewer initial families from which to select. Analysis of the role of allele frequencies within each selection design indicates that common trait alleles generally offer the most power, but similarities between the marker- and trait-allele frequencies are much more important than the trait-locus frequency alone. Some of the most widespread selection designs, such as single selection, yield power gains only when both the marker and quantitative trait loci (QTL) are relatively rare in the population. In contrast, discordant pairs and the extreme-proband design provide power for the broadest range of QTL-marker-allele frequency differences. Overall, proband selection from either tail provides the best balance of power, robustness, and simplicity of ascertainment for family-based association analysis.
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