Linkage disequilibrium maps constructed with common SNPs are useful for first-pass disease association screens

Taillon-Miller, Patricia; Sf, Saccone; Saccone, NL; Duan, Shenghui; Ef, Kloss; Eg, Lovins; Donaldson, Rachel; Phong, Angie; C, Ha; Flagstad, L; Miller, Shondra; Drendel, Amy L.; Lind, Denise L.; Rd, Miller; Jp, Rice; Kwok, Pui‐Yan

doi:10.1016/j.ygeno.2004.08.009

Cited by 18 publications

(12 citation statements)

References 23 publications

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“…To date, 10.1 million human reference SNPs have been deposited into the public database dbSNP (build 123, http://www.ncbi.nlm.nih.gov/SNP/) [1]. This immense data set provides a framework map of SNP markers that can be exploited for the mapping of genetic factors relevant in complex disease using whole-genome association studies [2][3][4], for the assembly of dense local SNP maps required in positional cloning projects [5,6], for admixture studies that take advantage of SNPs with large allele frequency differences between populations [7], and for genotyping projects including the International HapMap [8]. To facilitate these studies, however, the SNPs must be characterized in multiple individuals and populations to determine their utility.…”

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confidence: 99%

High-density single-nucleotide polymorphism maps of the human genome

Miller¹,

Phillips²,

Jo³

et al. 2005

Genomics

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Here we report a large, extensively characterized set of single-nucleotide polymorphisms (SNPs) covering the human genome. We determined the allele frequencies of 55,018 SNPs in African Americans, Asians (Japanese-Chinese), and European Americans as part of The SNP Consortium's Allele Frequency Project. A subset of 8333 SNPs was also characterized in Koreans. Because these SNPs were ascertained in the same way, the data set is particularly useful for modeling. Our results document that much genetic variation is shared among populations. For autosomes, some 44% of these SNPs have a minor allele frequency ≥10% in each population, and the average allele frequency differences between populations with different continental origins are less than 19%. However, the *Corresponding authors. Jong-Eun Lee is to be contacted at fax: +82 2 364 4778. Michael T. Boyce-Jacino, fax: +1 609 818 0054. PuiYan Kwok,

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confidence: 99%

High-density single-nucleotide polymorphism maps of the human genome

Miller¹,

Phillips²,

Jo³

et al. 2005

Genomics

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“…These papers, together with the present paper and Taillon-Miller et al [2004], are the only publications to our knowledge that implement the direct use of power calculations to select tag SNPs for genotyping in genetic association studies. Of these, only the present paper explicitly accounts for repulsion-phase LD and uses LD phase information in the selection algorithm.…”

Section: Discussionmentioning

confidence: 99%

“…Results will be presented as sample size requirements for fixed power and significance level, for a range of disease models and strength of LD between marker and disease. These sample size calculations were carried out using non-central w 2 distributions as we have described in Taillon-Miller et al [2004] Risch and Merikangas [1996], g 5 g 12 is the ''genotypic relative risk'' (GRR). For each multiplicative model we computed the corresponding sibling relative risk (l s ) using formulas rederived from Risch and Merikangas [1996] to correct known errors.…”

Section: Power Calculationsmentioning

confidence: 99%

“…We identified non-overlapping blocks of SNPs in strong LD using our algorithm as previously described [Taillon-Miller et al, 2004]. This algorithm defines an LD block to be a consecutive (relative to the map in use) set of at least three markers along with a cutoff threshold T and a disequilibrium coefficient L (e.g.…”

Section: Ld Data Analysis and Ld Tag Snp Selection Algorithmsmentioning

confidence: 99%

“…LD-based methods include the ''r 2 bin'' approach [Carlson et al, 2004;Hinds et al, 2005] which constructs bins of SNPs, not necessarily contiguous, that can each be represented by an SNP having high r 2 with all members of the bin. Here we present an alternative approach to SNP selection that expands on our previous work [Taillon-Miller et al, 2004]. This new method incorporates power calculations directly into the definition of LD blocks and the selection of tag SNPs.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Power‐based, phase‐informed selection of single nucleotide polymorphisms for disease association screens

Saccone

Rice

Saccone

2006

Genetic Epidemiology

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Single nucleotide polymorphisms (SNPs) are becoming widely used as genotypic markers in genetic association studies of common, complex human diseases. For such association screens, a crucial part of study design is determining what SNPs to prioritize for genotyping. We present a novel power-based algorithm to select a subset of tag SNPs for genotyping from a map of available SNPs. Blocks of markers in strong linkage disequilibrium (LD) are identified, and SNPs are selected to represent each block such that power to detect disease association with an underlying disease allele in LD with block members is preserved; all markers outside of blocks are also included in the tagging subset. A key, novel element of this method is that it incorporates information about the phase of LD observed among marker pairs to retain markers likely to be in coupling phase with an underlying disease locus, thus increasing power compared to a phase-blind approach. Power calculations illustrate important issues regarding LD phase and make clear the advantages of our approach to SNP selection. We apply our algorithm to genotype data from the International HapMap Consortium and demonstrate that considerable reduction in SNP genotyping may be attained while retaining much of the available power for a disease association screen. We also demonstrate that these tag SNPs effectively represent underlying variants not included in the LD analysis and SNP selection, by using leave-one-out tests to show that most (approximately 90%) of the "untyped" variants lying in blocks are in coupling-phase LD with a tag SNP. Additional performance tests using the HapMap ENCyclopedia of DNA Elements (ENCODE) regions show that the method compares well with the popular r2 bin tagging method. This work is a concrete example of how empirical LD phase may be used to benefit study design.

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The Pharmacogenomics of Personalized Medicine

Reid¹

2010

Pharmaceutical Sciences Encyclopedia

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The preclinical development of genetic data for application in the pharmacogenomics of disease therapy and management has become more complex than the earlier studies had suggested. The pharmacokinetic parameters determine the eventual distribution of the drug in the body including the concentration of the drug at the site of pharmacodynamic action. This article discusses various aspects of pharmacogenomics of personalized medicine, including molecular profiling technologies.

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Linkage disequilibrium maps constructed with common SNPs are useful for first-pass disease association screens

Cited by 18 publications

References 23 publications

High-density single-nucleotide polymorphism maps of the human genome

High-density single-nucleotide polymorphism maps of the human genome

Power‐based, phase‐informed selection of single nucleotide polymorphisms for disease association screens

The Pharmacogenomics of Personalized Medicine

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