Putting autoimmune disease genetic links to the test

March 15, 2017
DNA
Credit: NIH

Studies of autoimmune and inflammatory diseases have identified hundreds of genetic regions thought to be associated with these conditions. At the same time, studies of expression quantitative trait loci (eQTLs) have revealed the abundance of inherited variations in gene expression levels in the normal human population. While it is widely believed that the majority of disease-associated loci influence disease risk through regulatory variations in gene expression, this hypothesis has not been formally tested by verifying whether most of genetic loci influencing disease risk are also detectable as eQTLs. In an effort to examine this hypothesis, investigators at BWH and their colleagues took approximately 270 genetic loci associated with seven diseases and tried to map them back to causal genes using eQTLs in key immune cells.

They report their results in Nature Genetics.

The team was able to resolve 55 of these associations to candidate genes with strong statistical consistency with variations of baseline in unstimulated immune cells. However, this is only a small fraction - about 25 percent - of the examined. For the rest, the researchers did not observe any signal in the eQTL data that were consistent with autoimmune disease associations despite the fact that disease-relevant cell populations are easier to access from blood samples compared to other disease.

"Abundant caution must be exercised before pathological relevance is inferred for an observed eQTL simply on the basis of proximity to a disease association," the authors write. "Strong-evidence of a shared genetic effect should therefore be established before time-consuming and costly experimental dissection of such effects is undertaken."

Explore further: Immune cell genome differences underlie individual predisposition to several diseases

More information: Sung Chun et al, Limited statistical evidence for shared genetic effects of eQTLs and autoimmune-disease-associated loci in three major immune-cell types, Nature Genetics (2017). DOI: 10.1038/ng.3795

Related Stories

Immune cell genome differences underlie individual predisposition to several diseases

April 20, 2016
A new study has found a link between genomic variation and disease susceptibility. An A*STAR-led-team identified certain genomic variations associated with autoimmune, inflammatory and dermatological diseases in a type of ...

Changes in RNA splicing: a new mechanism for genetic risk in schizophrenia

February 27, 2017
New research has identified sections of DNA associated with altered regulation of gene expression underlying schizophrenia. The implicated loci contribute to schizophrenia risk by affecting alternative splicing, part of the ...

World-first genetic clues point to risk of blindness

February 27, 2017
Australian scientists have discovered the first evidence of genes that cause Macular Telangiectasia type 2 (MacTel), a degenerative eye disease which leads to blindness and is currently incurable and untreatable.

Molecular patterns of complex diseases

February 16, 2017
The Helmholtz Zentrum München has published results of the largest genome-wide association study on proteomics to date. An international team of scientists reports 539 associations between protein levels and genetic variants ...

Potential new asthma genes ID'd in genome-wide study

July 28, 2016
(HealthDay)—Potential new asthma genes have been identified in a genome-wide association study (GWAS) combined with subsequent lung expression quantitative trait loci (eQTL) analysis, according to research published online ...

Genetic overlapping in multiple autoimmune diseases may suggest common therapies

August 24, 2015
Scientists who analyzed the genes involved in 10 autoimmune diseases that begin in childhood have discovered 22 genome-wide signals shared by two or more diseases. These shared gene sites may reveal potential new targets ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

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.