How Genetics Affects Risk, Onset Of Common Diseases

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In a paper published online in the journal Nature, a team of deCODE scientists detail a major mechanism through which genetic factors contribute to major public health problems. In its work on the inherited components of dozens of common diseases, deCODE has discovered gene variants that significantly affect individual susceptibility or protection against disease.

In the common forms of these conditions -- such as obesity, type 2 diabetes and cardiovascular diseases -- deCODE has previously shown that genetic variants confer increased or decreased risk by upregulating or downregulating the activity of major biological pathways. As a result, these variants place individuals on a spectrum of risk, with most of the population clustered at roughly average risk and a smaller number of people at either significantly higher or lower risk.

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In today's paper, the deCODE team and collaborators from Merck demonstrate one of the principal ways in which the activity of biological pathways is functionally perturbed in a quintessentially complex condition: obesity. Through analysis of adipose tissue from some 1700 Icelandic participants in obesity research cohorts, the deCODE team showed in data derived from primary human tissue that variations in gene expression -- in the up-regulation or downregulation of how genes are translated into proteins -- have a major impact on several parameters of clinical obesity.

The deCODE team then used its unique resources for genome-wide linkage and association analysis to demonstrate that variability in gene expression, like overall risk for disease, has a significant inherited component that can be linked to specific versions of genetic markers. The paper, "Genetics of gene expression and its effect on disease," is published today on Nature's website, www.nature.com , and will appear in a subsequent print edition of the journal.

"One of the observations we have made in our work on the isolation of disease genes is that the genetic risk of common diseases is often conferred by variations in the sequence of the genome that affect expression of genes. Hence, one of the ways to approach the study of common diseases is through the analysis of gene expression. This paper provides a substantial contribution towards the understanding of gene expression in man and one example of how it can be used to expand our knowledge of one disease, namely obesity," said Kari Stefansson, CEO of deCODE.

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