Statistical test increases power of genetic studies of complex disease

May 7, 2014

The power of genome-wide association studies (GWAS) to detect genetic influences on human disease can be substantially increased using a statistical testing framework reported in the May issue of the journal Genetics.

Despite the proliferation of GWAS, the associations found so far have largely failed to account for the known effects of genes on complex disease—the problem of "missing heritability." Standard approaches also struggle to find combinations of multiple genes that affect disease risk in complex ways (known as genetic interactions).

The new framework enhances the ability to detect genetic associations and interactions by taking advantage of data from other genomic studies of the same population. Such information is increasingly abundant for many human populations.

The authors demonstrated that their method improves performance over standard approaches. They also re-examined real GWAS data to find promising new candidates for genetic interactions that affect bipolar disorder, , Crohn's disease, and rheumatoid arthritis.

"We think practically everyone who's ever done a case-control GWAS could benefit from reanalyzing their data in this way," said author Saharon Rosset, associate professor of statistics at Tel Aviv University.

"This paper offers a significant advance in mapping genes involved in disease. The approach makes use of available data to substantially improve the ability to identify genetic components of disease," said Mark Johnston, Editor-in-Chief of the journal Genetics.

Explore further: Gene combinations and interactions affect risk of Crohn's disease

More information: S. Kaufman and S. Rosset. Exploiting Population Samples to Enhance Genome-Wide Association Studies of Disease. Genetics May 2014 197:337-349 DOI: 10.1534/genetics.114.162511 Available online May 7, 2014. http://www.genetics.org/content/197/1/337

Related Stories

Gene combinations and interactions affect risk of Crohn's disease

August 23, 2013
A statistical model accounting for dozens of different genes in combination—and the interactions between them—is an important step forward in understanding the genetic factors affecting the risk of Crohn's disease (CD), ...

Study ties ABCC9 anomalies, sulfonylurea exposure to HS-Aging

April 29, 2014
A genome-wide association study (GWAS) led by Peter Nelson, MD, PhD, of the Sanders-Brown Center on Aging at the University of Kentucky, and David Fardo, PhD, of UK's Department of Biostatistics, has provided new insight ...

Genetic analysis reveals insights into the genetic architecture of OCD, Tourette syndrome

October 24, 2013
An international research consortium led by investigators at Massachusetts General Hospital (MGH) and the University of Chicago has answered several questions about the genetic background of obsessive-compulsive disorder ...

Genetic predisposition to liking amphetamine reduces risk of schizophrenia and ADHD

April 7, 2014
Genetic variants associated with enjoying the effects of d-amphetamine—the active ingredient in Adderall—are also associated with a reduced risk for developing schizophrenia and attention deficit hyperactivity disorder ...

Small variations in genetic code, previously thought to be inconsequential, can team up to have a big impact

May 2, 2014
(Medical Xpress)—Scientists at USC have definitively demonstrated that large sets of variations in the genetic code that do not individually appear to have much effect can collectively produce significant changes in an ...

Genetic variation linked to heart disease risk through RNA machinery

March 27, 2014
Researchers have pinpointed a new mechanism of how natural variation in our DNA alters an individual's risk for developing heart disease by interfering with the ability of a developmental gene to interact with a specialized ...

Recommended for you

Association found between abnormal cerebral connectivity and variability in the PPARG gene in developing preterm infants

December 12, 2017
(Medical Xpress)—A team of researchers with King's College London and the National Institute for Health Research Biomedical Research Centre, both in the U.K., has found what they describe as a strong association between ...

Large genetic study links tendency to undervalue future rewards with ADHD, obesity

December 11, 2017
Researchers at University of California San Diego School of Medicine have found a genetic signature for delay discounting—the tendency to undervalue future rewards—that overlaps with attention-deficit/hyperactivity disorder ...

Gene variants identified that may influence sexual orientation in men and boys

December 8, 2017
(Medical Xpress)—A large team of researchers from several institutions in the U.S. and one each from Australia and the U.K. has found two gene variants that appear to be more prevalent in gay men than straight men, adding ...

Disease caused by reduction of most abundant cellular protein identified

December 8, 2017
An international team of scientists and doctors has identified a new disease that results in low levels of a common protein found inside our cells.

Study finds genetic mutation causes 'vicious cycle' in most common form of amyotrophic lateral sclerosis

December 8, 2017
University of Michigan-led research brings scientists one step closer to understanding the development of neurodegenerative disorders such as ALS.

Mutations in neurons accumulate as we age: The process may explain normal cognitive decline and neurodegeneration

December 7, 2017
Scientists have wondered whether somatic (non-inherited) mutations play a role in aging and brain degeneration, but until recently there was no good technology to test this idea. A study published online today in Science, ...

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.