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Editorials

Contemporary Approaches to Gene Discovery

Progress Toward Personalized Medicine?

Ingrid B. Borecki, PhD

From the Division of Statistical Genomics, Washington University School of Medicine, St Louis, Mo.

Correspondence to Ingrid B. Borecki, PhD, Division of Statistical Genomics, Washington University School of Medicine, 4444 Forest Park Boulevard, Box 8506, St Louis, MO 63108. E-mail: iborecki@wustl.edu

Key Words: gene discovery • GWA • predictive index • atherosclerosis • genetics

An extract of the first 250 words of the full text is provided, because this article has no abstract.

It is broadly recognized that cardiovascular disease has a familial basis; however, progress in identifying the causative genes has been slow. The goal of identifying disease genes or those genes influencing cardiovascular risk factor phenotypes is at the heart of personalized medicine, giving rise to the hope that such knowledge will identify new therapeutic targets, help identify individuals at high risk to receive interventional therapy, and perhaps help to refine prognosis once clinical disease is present. Testing of candidate genes and genome-wide searches using anonymous, highly polymorphic markers via linkage studies has produced some information regarding the location of putative trait genes but has left open the question of precisely which genes are at play, which are the relevant variants, and how they function to modify disease risk. The advent of high-density arrays, in which up to a million single-nucleotide polymorphisms can be assessed in thousands of subjects in a cost-effective manner, has opened the door to an unprecedented level of inquiry. Much finer mapping information can be obtained because this approach relies on linkage disequilibrium, which extends over much shorter distances than does linkage.

Articles see pp 7 and 63

There is currently vigorous activity in almost all domains of complex human diseases to apply genome-wide association scans (GWAS) to identify trait loci. In this issue of Circulation: Cardiovascular Genetics, Ding and Kullo¹ review the basic tenants of this approach and the progress that has been made toward gene discovery in the area of atherosclerotic heart disease. The . . . [Full Text of this Article]

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