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Chunk #6 — INTRODUCTION

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The combination of a genome-wide association study of lymphocyte count and analysis of gene expression data reveals novel asthma candidate genes.
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The results of these studies suggest that integrating gene expression and GWAS data may be an effective filtering and discovery approach, allowing one to uncover novel weakly associated genetic variants using easily annotated functional mechanisms. Here, we pursue a similar approach by leveraging gene expression data to identify candidate genes that influence inter-individual variation in lymphocyte counts in the Hutterites. The Hutterites offer a unique opportunity to study genetic regulation of complex traits because extensive data on a wide range of phenotypes and genome-wide genotype data for a large number of individuals are available for this founder population. In addition, the communal lifestyle practiced by the Hutterites leads to remarkably uniform environmental exposures (24). As lymphocyte counts were previously significantly associated (P = 1 × 10−4) with asthma in the Hutterites (25), we also extended our approach to map novel asthma susceptibility loci in an independent asthma GWAS data set.