A single SNP that confers increased risk if inherited from the father, but is protective if inherited from the mother
Reykjavik, ICELAND, December 16, 2009 – Scientists at deCODE genetics, Inc. (Nasdaq:DCGN) publish in the journal Nature the discovery of a version of a common single-letter variant in the sequence of the human genome (SNP) with a major impact on susceptibility to type 2 diabetes (T2D). The impact of the T2D variant is not only large, but unusual: if an individual inherits it from their father, the variant increases risk of T2D by more than 30% compared to those who inherit the non T2D-linked version; if inherited maternally, the variant lowers risk by more than 10% compared to the non T2D-linked version. Nearly one quarter of those studied have the highest risk combination of the versions of this SNP, putting them at a roughly 50% greater lifetime risk of T2D than the quarter with the protective combination. This is the second largest effect of any genetic variant for T2D apart from SNPs in TCF7L2, discovered by deCODE in 2006.
“We could make this discovery beacause we are in the unique position of being able to distinguish what is inherited from the mother from what is inherited from the father. This we can do because of the large amount of data we have assembled on the Icelandic population. These data empower us in many ways. For example, using our ability to impute sequence data, we can multiply by 100 times the amount of information generated by sequencing one individual. We can use these tools to discover and integrate rarer variants into our tests and scans, identify drug targets for licensing, and put our know-how at the disposal of our service customers. We believe that this is an important advantage for conducting large-scale whole sequence studies over the next couple of years,” said Kari Stefansson, CEO of deCODE.
Because the risk is inherited and varies in this way, the SNP, located on chromsome 11, had never been linked to T2D even though it had been genotyped in large, traditional genome-wide association studies (GWAS). These do not distinguish between paternally and maternally inherited SNPs. But deCODE can track the parental origin of virtually any SNP in the genome of the tens of thousands of Icelandic participants in the company’s gene discovery work. In this study, deCODE used its population-wide genealogy database and proprietary statistical tools to determine the parent of origin of a number of SNPs in some 40,000 Icelandic participants in the company’s gene discovery programs. Some of these SNPs had previously been associated with different diseases and are located near “imprinted” genes – genes in which only the maternally or paternally inherited copy is “switched-on” to encode a protein. Five of these, one each in breast and skin cancer and three in T2D, showed that the parental origin of the variants affects the risk they confer.
The paper, “Parental origin of sequence variants associated with complex diseases,” is published online at www.nature.com, and will appear in the December 17 print edition.
This study was conducted by deCODE’s wholly-owned, Iceland-based human genetics subsidiary, which continues all of its human genetics operations, including gene discovery and product and service offerings. Concurrent with deCODE’s recent petition for bankruptcy protection in the United States, deCODE has entered into and filed with the court an asset purchase agreement with Saga Investments LLC (Saga) to sell its Iceland-based subsidiary as a going concern, including latter’s product lines and service businesses. This agreement, pursuant to Section 363 of the Bankruptcy Code, is subject to a number of contingencies, including a competitive bidding procedure and court approval in accordance with bankruptcy law.
deCODE is a global leader in analysing and understanding the human genome. deCODE has identified key variations in the sequence of the genome conferring increased risk of major public health challenges from cardiovascular disease to cancer, and employs its gene discovery engine to develop DNA-based tests to assess individual risk of common diseases; to license its tests and intellectual property to partners; and to provide comprehensive, leading- edge contract services to companies and research institutions around the globe. Through its CLIA- and CAP-certified laboratory deCODE offers DNA-based tests for gauging risk and empowering prevention of common diseases, including deCODE T2™ for type 2 diabetes; deCODE AF™ for atrial fibrillation and stroke; deCODE MI™ for heart attack; deCODE ProstateCancer™ for prostate cancer; deCODE Glaucoma™ for a major type of glaucoma; and deCODE BreastCancer, for the common forms of breast cancer. Through its pioneering personal genome analysis service deCODEme™, deCODE enables individuals to better understand their risk of dozens of common diseases and to learn about their ancestry and other traits. Visit us on the web at www.decode.com; at www.decodediagnostics.com; at www.decodeme.com; and on our blog at www.decodeyou.com.
Any statements contained in this presentation that relate to future plans, events or performance are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding deCODE’s expectations concerning the bankruptcy process and the continuation of day-to-day operations. deCODE’s actual results could differ materially from those anticipated in the forward-looking statements as a result of risks and uncertainties, including, without limitation, (1) the impact of the announcement of its bankruptcy filing on deCODE’s operations; (2) the ability of deCODE to maintain sufficient debtor-in-possession financing to fund its operations and the expenses of the Chapter 11 proceeding; (3) the ability of deCODE to obtain court approval of its motions in the Chapter 11 proceeding; (4) the outcome and timing of the proposed sale of deCODE’s assets, including deCODE’s ability to close a transaction with SagaInvestments, LLC or any other purchaser; (5) the uncertainty associated with motions by third parties in the bankruptcy proceeding; (6) deCODE’s ability to obtain and maintain normal terms with vendors and service providers and contracts that are critical to its operation; and (7) other risks identified in deCODE’s filings with the Securities and Exchange Commission, including, without limitation, the risk factors identified in our most recent Annual Report on Form 10-K and any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. deCODE undertakes no obligation to update or alter these forward-looking statements as a result of new information, future events or otherwise.