Dec 17 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 because 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 http://www.nature.com, and will appear in
the December 17 print edition.
SOURCE DeCODE Genetics Inc