A scan statistic for identifying chromosomal patterns of SNP association.

Full Abstract

We have developed a single nucleotide polymorphism (SNP) association scan statistic that takes into account the complex distribution of the human genome variation in the identification of chromosomal regions with significant SNP associations. This scan statistic has wide applicability for genetic analysis, whether to identify important chromosomal regions associated with common diseases based on whole-genome SNP association studies or to identify disease susceptibility genes based on dense SNP positional candidate studies. To illustrate this method, we analyzed patterns of SNP associations on chromosome 19 in a large cohort study. Among 2,944 SNPs, we found seven regions that contained clusters of significantly associated SNPs. The average width of these regions was 35 kb with a range of 10-72 kb. We compared the scan statistic results to Fisher's product method using a sliding window approach, and detected 22 regions with significant clusters of SNP associations. The average width of these regions was 131 kb with a range of 10.1-615 kb. Given that the distances between SNPs are not taken into consideration in the sliding window approach, it is likely that a large fraction of these regions represents false positives. However, all seven regions detected by the scan statistic were also detected by the sliding window approach. The linkage disequilibrium (LD) patterns within the seven regions were highly variable indicating that the clusters of SNP associations were not due to LD alone. The scan statistic developed here can be used to make gene-based or region-based SNP inferences about disease association.(c) 2006 Wiley-Liss, Inc.

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Author information

Author/s: Sun, Yan V (YV); Levin, Albert M (AM); Boerwinkle, Eric (E); Robertson, Henry (H); Kardia, Sharon L R (SL);

Affiliation: Department of Epidemiology, University of Michigan, 611 Church Street, Ann Arbor, MI 48104, USA.

Grants: HL 54457 (Agency:NHLBI NIH HHS) ; HL 68737 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Genetic epidemiology (Genet Epidemiol), published in United States. (Language: eng)

Reference: 2006-Nov; vol 30 (issue 7) : pp 627-35

Dates: Created 2006/10/30; Completed 2007/01/19; Revised 2007/12/03;

PMID: 16858698, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Humans
Poisson Distribution
Polymorphism, Single Nucleotide - genetics

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