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A Mutation Discovered In Iceland That Increases Risks Of Osteoporosis And Certain Cancers

REYKJAVIK, Iceland, May 5, 2013 /PRNewswire/ --

deCODE genetics (an Amgen subsidiary) and Illumina, global leaders in analyzing and understanding the human genome, together with scientists from the National Hospital of Iceland and the University of Iceland reported today in the journal Nature the identification of a rare nonsense mutation that confers high risk of osteoporosis and osteoporosis related traits. The mutation was also found to dramatically increase the risk of squamous cell carcinoma of the skin, biliary tract cancer, and to promote an imbalance in blood electrolytes and late onset of menarche.

"Our findings strongly implicate LGR4 in the pathogenesis of osteoporosis as well as various other human diseases, including certain cancers," said study lead author Kari Stefánsson, M.D., Dr. Med., President of deCODE Genetics. "That this one mutation increases the risk of many diseases is not surprising. The mutation impacts an important signaling pathway known as Wnt, that contributes to the function of many cell types."

In this study, the research team searched for gene mutations-or other variations in the genome-that may have a direct effect on the risk of pathologically low-bone density among a large set of sequence variants.

Using deCODE's whole genome sequencing of 2,230 Icelanders, 34 million sequence variants were identified and subsequently analyzed against 4,931 persons with low-bone density disease and a large control population. From this approach, the research team discovered the nonsense mutation in LGR4 and its large effect on osteoporosis and osteoporosis related traits.

The effect of the LGR4 mutation on many other conditions was further investigated taking advantage of a large number of human diseases and other traits that are available at deCODE. Through this effort the mutation was also found to increase the risk of squamous cell carcinoma of the skin and biliary tract cancer as well as to cause blood electrolyte imbalance and late onset of menarche.

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