First publication of genome-wide association study leveraging deCODE’s population approach; Finding to be integrated into deCODE’s DNA-based diagnostics program

A team of deCODE scientists, along with academic colleagues from the United States, Iceland, Spain and the Netherlands, today publish the discovery of a second genetic variant on chromosome 8q24 conferring risk of prostate cancer. This is the first publication of deCODE’s new discoveries emerging from the application of genome-wide SNP association technologies to the company’s population genetics resources. The paper, entitled “Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24,” is published today in the online edition of Nature genetics, at, and will be published in a subsequent print edition of the journal.

Last May, deCODE published its discovery of the first common genetic variant ever shown to associate with significantly increased risk of prostate cancer in the general population. That variant, located on chromosome 8q24 and identified through linkage analysis of men from more than 300 families in Iceland followed by detailed genotyping of the chromosomal region and case-control analyses, confers an approximately 60% increase in risk of the disease. It is also more than twice as common among African American men than it is among those of European ancestry, contributing to the higher incidence of the disease among African Americans.

The second variant was identified through a genome-wide association scan of 4,500 Icelandic cases and controls using the Illumina HumanHap300 Bead Chip, which types more than 300,000 SNPs across the genome. The strongest association detected was the variant identified last year, but the deCODE team then applied deCODE’s tools for constructing and testing haplotypes – groups of markers – of multiple SNPs, in order to investigate more complex associations with the disease that might have eluded the simpler analysis. This analysis identified a 14-marker haplotype and a closely correlated SNP not included in the genome-wide scan that was replicated in cohorts of European descent from Chicago, Spain and the Netherlands. The variant was found in about 3% of controls and roughly twice that number of prostate cancer patients. However, in an African American case-control cohort from Baltimore, the variant was found in about 30% of controls and 42% of patients, corresponding to a slightly lower increase in risk than in the European ancestry cohorts, but, because of its much higher frequency, accounting for one quarter of prostate cancer cases among African Americans.

Taken together, the two variants in this region of chromosome 8 discovered by deCODE account for about 11-13% of prostate cancer among men of European descent, but approximately 30% of the disease burden among African Americans. These variants, which are suggestively linked to earlier age at onset, may therefore be useful for identifying men for whom more frequent screening and more aggressive intervention may be beneficial, and deCODE intends to utilize these findings to develop a DNA-based test for the variants to improve prevention and treatment.