Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study

INTRODUCTION:Subclinical atherosclerosis (SCA) measures in multiple arterial beds are heritable phenotypes that are associated with increased incidence of cardiovascular disease. We conducted a genome-wide association study (GWAS) for SCA measurements in the community-based Framingham Heart Study.METHODS:Over 100,000 single nucleotide polymorphisms (SNPs) were genotyped (Human 100K GeneChip, Affymetrix) in 1345 subjects from 310 families. We calculated sex-specific age-adjusted and multivariable-adjusted residuals in subjects tested for quantitative SCA phenotypes, including ankle-brachial index, coronary artery calcification and abdominal aortic calcification using multi-detector computed tomography, and carotid intimal medial thickness (IMT) using carotid ultrasonography. We evaluated associations of these phenotypes with 70,987 autosomal SNPs with minor allele frequency [greater than or equal to] 0.10, call rate [greater than or equal to] 80%, and Hardy-Weinberg p-value [greater than or equal to] 0.001 in samples ranging from 673 to 984 subjects, using linear regression with generalized estimating equations (GEE) methodology and family-based association testing (FBAT). Variance components LOD scores were also calculated.RESULTS:There was no association result meeting criteria for genome-wide significance, but our methods identified 11 SNPs with p < 10-5 by GEE and five SNPs with p < 10-5 by FBAT for multivariable-adjusted phenotypes. Among the associated variants were SNPs in or near genes that may be considered candidates for further study, such as rs1376877 (GEE p < 0.000001, located in ABI2) for maximum internal carotid artery IMT and rs4814615 (FBAT p = 0.000003, located in PCSK2) for maximum common carotid artery IMT. Modest significant associations were noted with various SCA phenotypes for variants in previously reported atherosclerosis candidate genes, including NOS3 and ESR1. Associations were also noted of a region on chromosome 9p21 with CAC phenotypes that confirm associations with coronary heart disease and CAC in two recently reported genome-wide association studies. In linkage analyses, several regions of genome-wide linkage were noted, confirming previously reported linkage of internal carotid artery IMT on chromosome 12. All GEE, FBAT and linkage results are provided as an open-access results resource at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:The results from this GWAS generate hypotheses regarding several SNPs that may be associated with SCA phenotypes in multiple arterial beds. Given the number of tests conducted, subsequent independent replication in a staged approach is essential to identify genetic variants that may be implicated in atherosclerosis.

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Retrieval by Shape Population: An Index Tree Approach

Based on our previous work in deformable shape model-based object detection, a new method is proposed that uses index trees for organizing shape features to support content-based retrieval applications. In the proposed strategy, different shape feature sets can be used in index trees constructed for object detection and shape similarity comparison respectively. There is a direct correspondence between the two shape feature sets. As a result, application-specific features can be obtained efficiently for shape-based retrieval after object detection. A novel approach is proposed that allows retrieval of images based on the population distribution of deformed shapes in each image. Experiments testing these new approaches have been conducted using an image database that contains blood cell micrographs. The precision vs. recall performance measure shows that our method is superior to previous methods.

Index Trees for Efficient Deformable Shape-based Retrieval

An improved method for deformable shape-based image indexing and retrieval is described. A pre-computed index tree is used to improve the speed of our previously reported on-line model fitting method; simple shape features are used as keys in a pre-generated index tree of model instances. In addition, a coarse to fine indexing scheme is used at different levels of the tree to further improve speed while maintaining matching accuracy. Experimental results show that the speedup is significant, while accuracy of shape-based indexing is maintained. A method for shape population-based retrieval is also described. The method allows query formulation based on the population distributions of shapes in each image. Results of population-based image queries for a database of blood cell micrographs are shown.

Authenticated Index Structures for Outsourced Database Systems

In outsourced database (ODB) systems the database owner publishes its data through a number of remote servers, with the goal of enabling clients at the edge of the network to access and query the data more efficiently. As servers might be untrusted or can be compromised, query authentication becomes an essential component of ODB systems. Existing solutions for this problem concentrate mostly on static scenarios and are based on idealistic properties for certain cryptographic primitives. In this work, first we define a variety of essential and practical cost metrics associated with ODB systems. Then, we analytically evaluate a number of different approaches, in search for a solution that best leverages all metrics. Most importantly, we look at solutions that can handle dynamic scenarios, where owners periodically update the data residing at the servers. Finally, we discuss query freshness, a new dimension in data authentication that has not been explored before. A comprehensive experimental evaluation of the proposed and existing approaches is used to validate the analytical models and verify our claims. Our findings exhibit that the proposed solutions improve performance substantially over existing approaches, both for static and dynamic environments.

Authenticated Index Structures for Aggregation Queries in Outsourced Databases

In an outsourced database system the data owner publishes information through a number of remote, untrusted servers with the goal of enabling clients to access and query the data more efficiently. As clients cannot trust servers, query authentication is an essential component in any outsourced database system. Clients should be given the capability to verify that the answers provided by the servers are correct with respect to the actual data published by the owner. While existing work provides authentication techniques for selection and projection queries, there is a lack of techniques for authenticating aggregation queries. This article introduces the first known authenticated index structures for aggregation queries. First, we design an index that features good performance characteristics for static environments, where few or no updates occur to the data. Then, we extend these ideas and propose more involved structures for the dynamic case, where the database owner is allowed to update the data arbitrarily. Our structures feature excellent average case performance for authenticating queries with multiple aggregate attributes and multiple selection predicates. We also implement working prototypes of the proposed techniques and experimentally validate the correctness of our ideas.