Gene data tool advances prospects for personalized medicine

Oct 09, 2009

A sophisticated computational algorithm, applied to a large set of gene markers, has achieved greater accuracy than conventional methods in assessing individual risk for type 1 diabetes.

A research team led by Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia, suggests that their technique, applied to appropriate complex multigenic diseases, improves the prospects for personalizing medicine to an individual's . The study appears in the October 9 issue of the online journal .

Genome-wide association studies (GWAS), in which automated genotyping tools scan the entire seeking gene variants that contribute to disease risk, have yet to fulfill their potential in allowing physicians to accurately predict a person's individual risk for a disease, and thus guide prevention and treatment strategies.

The authors say that for many diseases, the majority of contributory genes remain undiscovered, and studies that make selective use of a limited number of selected, validated gene variants yield very limited results. For many of the recent studies, the area under the curve (AUC), a method of measuring the accuracy of risk assessment, amounts to 0.55 to 0.60, little better than chance (0.50), and thus falling short of clinical usefulness.

Hakonarson's team broadened their net, going beyond cherry-picked susceptibility genes to searching a broader collection of markers, including many that have not yet been confirmed, but which reach a statistical threshold for gene interactions or association with a disease. Although this approach embraces some false positives, its overall statistical power produces robust predictive results.

By applying a "machine-learning" algorithm that finds interactions among data points, say the authors, they were able to identify a large ensemble of genes that interact together. After applying their algorithm to a GWAS dataset for , they generated a model and then validated that model in two independent datasets. The model was highly accurate in separating type 1 diabetes cases from control subjects, achieving AUC scores in the mid-80s.

The authors say it is crucial to choose a target disease carefully. Type 1 diabetes is known to be highly heritable, with many risk-conferring genes concentrated in one region—the major histocompatibility complex. For other complex diseases, such as psychiatric disorders, which do not have major-effect genes in concentrated locations, this approach might not be as effective.

Furthermore, the authors' risk assessment model might not be applicable to mass population-level screening, but rather could be most useful in evaluating siblings of affected patients, who already are known to have a higher risk for the specific disease. The authors say that their approach is more effective, and costs less, than human leukocyte antigen (HLA) testing, currently used to assess type 1 diabetes risk in clinical settings.

Source: Children's Hospital of Philadelphia (news : web)

Explore further: Gene clues to glaucoma risk

add to favorites email to friend print save as pdf

Related Stories

Researchers continue to find genes for type 1 diabetes

Oct 14, 2008

Genetics researchers have identified two novel gene locations that raise the risk of type 1 diabetes. As they continue to reveal pieces of the complicated genetic puzzle for this disease, the researchers expect to improve ...

More findings on gene involved in childhood asthma

Sep 15, 2008

Asthma researchers have found that a gene variant known to raise the risk of childhood asthma in European children plays a similar role in white American children, but not in African American children.

Gene discovered for type 1 diabetes in children

Jul 15, 2007

Pediatrics researchers at The Children’s Hospital of Philadelphia and McGill University in Montreal have identified a gene variant that raises a child’s risk for type 1 diabetes, formerly called juvenile diabetes. As ...

Recommended for you

A nucleotide change could initiate fragile X syndrome

15 hours ago

Researchers reveal how the alteration of a single nucleotide—the basic building block of DNA—could initiate fragile X syndrome, the most common inherited form of intellectual disability. The study appears ...

Gene clues to glaucoma risk

Aug 31, 2014

Scientists on Sunday said they had identified six genetic variants linked to glaucoma, a discovery that should help earlier diagnosis and better treatment for this often-debilitating eye disease.

Mutation disables innate immune system

Aug 29, 2014

A Ludwig Maximilian University of Munich team has shown that defects in the JAGN1 gene inhibit the function of a specific type of white blood cells, and account for a rare congenital immune deficiency that ...

Study identifies genetic change in autism-related gene

Aug 28, 2014

A new study from Bradley Hospital has identified a genetic change in a recently identified autism-associated gene, which may provide further insight into the causes of autism. The study, now published online in the Journal of ...

NIH issues finalized policy on genomic data sharing

Aug 27, 2014

The National Institutes of Health has issued a final NIH Genomic Data Sharing (GDS) policy to promote data sharing as a way to speed the translation of data into knowledge, products and procedures that improve health while ...

User comments : 0