'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

Psychiatric disorders share an underlying genetic basis

June 21, 2018
Psychiatric disorders such as schizophrenia and bipolar disorder often run in families. In a new international collaboration, researchers explored the genetic connections between these and other disorders of the brain at ...

Deep data dive helps predict cerebral palsy

June 21, 2018
When University of Delaware molecular biologist Adam Marsh was studying the DNA of worms living in Antarctica's frigid seas to understand how the organisms managed to survive—and thrive—in the extremely harsh polar environment, ...

Genetic variation in progesterone receptor tied to prematurity risk, study finds

June 21, 2018
Humans have unexpectedly high genetic variation in the receptor for a key pregnancy-maintaining hormone, according to research led by scientists at the Stanford University School of Medicine. The finding may help explain ...

Shared genetics may shape treatment options for certain brain disorders

June 20, 2018
Symptoms of schizophrenia and bipolar disorder, including psychosis, depression and manic behavior, have both shared and distinguishing genetic factors, an international consortium led by researchers from Vanderbilt University ...

Scientists unravel DNA code behind rare neurologic disease

June 20, 2018
Scientists conducting one of the largest full DNA analyses of a rare disease have identified a gene mutation associated with a perplexing brain condition that blinds and paralyzes patients.

Simple sugar delays neurodegeneration caused by enzyme deficiency

June 20, 2018
A new therapeutic approach may one day delay neurodegeneration typical of a disease called mucopolysaccharidoses IIIB (MPS IIIB). Neurodegeneration in this condition results from the abnormal accumulation of essential cellular ...

0 comments

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.