期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 74, 期 1, 页码 106-120出版社
CELL PRESS
DOI: 10.1086/381000
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资金
- NHLBI NIH HHS [U01 HL066642, HL66682, HL66642, U01 HL066682] Funding Source: Medline
- NIEHS NIH HHS [N01ES15478] Funding Source: Medline
- NIMH NIH HHS [R01 MH059520, R37 MH059520, MH59520] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL066642, U01HL066682] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [N01ES15478] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R37MH059520, R01MH059520] Funding Source: NIH RePORTER
Common genetic polymorphisms may explain a portion of the heritable risk for common diseases. Within candidate genes, the number of common polymorphisms is finite, but direct assay of all existing common polymorphism is inefficient, because genotypes at many of these sites are strongly correlated. Thus, it is not necessary to assay all common variants if the patterns of allelic association between common variants can be described. We have developed an algorithm to select the maximally informative set of common single-nucleotide polymorphisms (tagSNPs) to assay in candidate-gene association studies, such that all known common polymorphisms either are directly assayed or exceed a threshold level of association with a tagSNP. The algorithm is based on the r(2) linkage disequilibrium (LD) statistic, because r(2) is directly related to statistical power to detect disease associations with unassayed sites. We show that, at a relatively stringent r(2) threshold (r(2) > 0.8), the LD-selected tagSNPs resolve >80% of all haplotypes across a set of 100 candidate genes, regardless of recombination, and tag specific haplotypes and clades of related haplotypes in nonrecombinant regions. Thus, if the patterns of common variation are described for a candidate gene, analysis of the tagSNP set can comprehensively interrogate for main effects from common functional variation. We demonstrate that, although common variation tends to be shared between populations, tagSNPs should be selected separately for populations with different ancestries.
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