'Filter' hones GWAS results to help researchers avoid dead ends

March 5, 2018, Johns Hopkins University School of Medicine
Credit: CC0 Public Domain

A genetics research team at Johns Hopkins Medicine has solved a dilemma facing researchers who use genomewide association studies (GWAS) by developing a new approach that strategically "filters" which genes are worth further study. The researchers hope this strategy will accelerate the study of diseases such as Parkinson's, Alzheimer's, schizophrenia and even addiction by helping researchers avoid "dead-end paths." They are optimistic that this strategy will gain widespread use and will save researchers time and money.

The findings were published March 1 in The American Journal of Human Genetics.

GWAS identify regions of the genome that can contain hundreds of potentially affected by a mutation. Selecting a gene to study from these extensive lists had been highly speculative. At best, the scientists say, there is a 50-50 chance that the gene closest to a mutation will even be active in the cell types affected by a .

"We are in a scenario where we can collect massive amounts of genetic data using GWAS, but are realizing that does not provide the biological context we need in order to understand the results," says Andy McCallion, Ph.D., assistant director of the graduate program and associate professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine.

McCallion's strategy to make sense of all this data looks at the in cells affected by a disease, groups of genes that interact with one another, their vulnerability to mutation and information from past scientific studies to filter more than a thousand gene candidates for disease risk down to just a handful within any one implicated region.

The focused on Parkinson's disease, which impacts dopamine neurons in the brain. GWAS identify 49 sections of the genome that have a mutation relevant to Parkinson's disease, says McCallion. By using the strategy, he and his team were able to filter down the thousands of genes in these sections to an average of two per region.

The researchers then asked whether the genes they found include those previously found to cause Parkinson's disease. Of the genes involved in Parkinson's disease that are present in indicated regions, the strategy captured all but one. "However, the one we didn't capture is not expressed in dopaminergic neurons," explains McCallion. "This gives us confidence that the other genes pointed out will be important to the disease."

The researchers hope to study the biological contexts of Parkinson's disease and other neurological diseases in the same way. They plan to investigate whether age, environment and disease state will allow them to hone the filter further for Parkinson's disease.

Explore further: Genetic defects in the cell's 'waste disposal system' linked to Parkinson's disease

More information: Paul W. Hook et al, Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease, The American Journal of Human Genetics (2018). DOI: 10.1016/j.ajhg.2018.02.001

Related Stories

Genetic defects in the cell's 'waste disposal system' linked to Parkinson's disease

November 14, 2017
An international study has shed new light on the genetic factors associated with Parkinson's disease, pointing at a group of lysosomal storage disorder genes as potential major contributors to the onset and progression of ...

Research discovers possible link between Crohn's and Parkinson's in Jewish population

January 11, 2018
Mount Sinai Researchers have just discovered that patients in the Ashkenazi Jewish population with Crohn's disease (a chronic inflammatory of the digestive system) are more likely to carry the LRRK2 gene mutation. This gene ...

Caffeine level in blood may help diagnose people with Parkinson's disease

January 3, 2018
Testing the level of caffeine in the blood may provide a simple way to aid the diagnosis of Parkinson's disease, according to a study published in the January 3, 2018, online issue of Neurology, the medical journal of the ...

Failure in recycling cellular membrane may be a trigger of Parkinson's

February 23, 2017
A genetic mutation found in patients with early-onset Parkinson's disease has been used to create a mouse model of the disease. The advance adds to growing evidence that—at least in a subset of patients—the neurodegenerative ...

Conversion of brain cells offers hope for Parkinson's patients

April 11, 2017
Researchers at Karolinska Institutet have made significant progress in the search for new treatments for Parkinson's disease. By manipulating the gene expression of non-neuronal cells in the brain, they were able to produce ...

An important study for Parkinson's disease: Researchers uncover mechanism regulating dopamine levels in the brain

December 11, 2014
Researchers in Montréal led by Jacques Drouin, D.Sc., uncovered a mechanism regulating dopamine levels in the brain by working on a mouse model of late onset Parkinson's disease. The study, conducted in collaboration with ...

Recommended for you

New methods find undiagnosed genetic diseases in electronic health records

March 15, 2018
Patients diagnosed with heart failure, stroke, infertility and kidney failure could actually be suffering from rare and undiagnosed genetic diseases.

Hundreds of genes linked to intelligence in global study

March 14, 2018
More than 500 genes linked to intelligence have been identified in the largest study of its kind. Scientists compared variation in DNA in more than 240,000 people from around the world, to discover which genes are associated ...

Study finds that genes play a role in empathy

March 12, 2018
A new study published today suggests that how empathic we are is not just a result of our upbringing and experience but also partly a result of our genes.

Large-scale genetic study provides new insight into the causes of stroke

March 12, 2018
An international research consortium studying 520,000 individuals from around the world has identified 22 new genetic risk factors for stroke, thus tripling the number of gene regions known to affect stroke risk. The results ...

Study suggests some CpGs in the genome can be hemimethylated by design

March 9, 2018
A pair of researchers at Emory University has found that some CpGs in the genome can be hemimethylated by design, rather than by chance. In their paper published in the journal Science, Chenhuan Xu and Victor Corces describe ...

Intravenous arginine benefits children after acute metabolic strokes

March 9, 2018
Children with mitochondrial diseases who suffered acute metabolic strokes benefited from rapid intravenous treatment with the amino acid arginine, experiencing no side effects from the treatment. The diseases were caused ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.