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US 8,796,182 B2Granted
Genetic markers associated with risk of diabetes mellitus
AssigneedeCODE Genetics ehf.
InventorsValgerdur Steinthorsdottir, Gudmar Thorleifsson, Daniel Gudbjartsson, Gisli Masson, Augustine Kong
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Abstract
The invention relates to variants that predispose to risk of type 2 diabetes, basal cell carcinoma and breast cancer. It has been discovered that certain genetic variants confer risk of these diseases when inherited from one parent, but not the other. The invention provides methods of disease management, including diagnostic methods, utilizing such parental origin effects.
Claims16
A method of determining a susceptibility to type 2 diabetes in a human individual, the method comprising:
- analyzing nucleic acid from a biological sample obtained from the individual with respect to the identity of at least one allele of at least one polymorphic marker, using a method that comprises at least one nucleic acid analysis technique selected from:
- analysis using a whole genome SNP chip, single-stranded conformational polymorphism (SSCP) assay, restriction fragment length polymorphism (RFLP), automated fluorescent sequencing;
- clamped denaturing gel electrophoresis (CDGE);
- denaturing gradient gel electrophoresis (DGGE), mobility shift analysis, restriction enzyme analysis, heteroduplex analysis, chemical mismatch cleavage (CMC), RNase protection assays, use of polypeptides that recognize nucleotide mismatches, allele-specific PCR, sequence analysis, and SNP genotyping,
- determining parental origin of the at least one allele of the at least one polymorphic marker, wherein different parental origins of the at least one allele are associated with different susceptibilities to type 2 diabetes in humans, and wherein the at least one polymorphic marker is selected from the group consisting of rs2334499, and markers in linkage disequilibrium therewith, wherein the linkage disequilibrium is characterized by a value for r2 of at least 0.2, and
- determining a susceptibility to type 2 diabetes for the individual from the nucleic acid analysis and from the parental origin of said at least one allele,
- wherein a paternal origin at-risk T allele of rs2334499 or a marker allele in linkage disequilibrium therewith is determined to be present in the nucleic acid, and the step of determining a susceptibility to type 2 diabetes for the individual includes calculating a risk score that includes a relative risk (RR) or odds ratio (OR) of at least 1.1 attributed to the paternal origin at-risk allele being present in the nucleic acid;
- or
- wherein a maternal origin protective T allele of rs2334499 or a marker allele in linkage disequilibrium therewith is determined to be present in the nucleic acid, and the step of determining susceptibility to type 2 diabetes for the individual includes calculating a risk score that includes a RR or OR of less than 0.9 attributed to the maternal origin protective allele being present in the nucleic acid;
- and
- wherein the presence of a paternal origin at-risk allele for the at least one marker in the nucleic acid is indicative of an increased susceptibility to type 2 diabetes for the individual, and the presence of a maternal origin protective allele for the at least one marker in the nucleic acid is indicative of a decreased susceptibility to type 2 diabetes for the individual.
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