Biostatistics approach to genetics yields new clues to roots of autism

February 3, 2014 by Leslie Church
Biostatistics approach to genetics yields new clues to roots of autism
Results from a statistical analysis shows a cluster of SNPs — single nucleotide polymorphisms — in one section of a single gene, indicating the location of a mutation likely linked to autism.

(Medical Xpress)—A study is only as good as the tools used to analyze it. One of those tools is statistics, and while biologists and chemists set up and run the experiments, statisticians are at work tinkering with the math that makes sense of all the data. Researchers at The Rockefeller University have recently developed a novel statistical method for genetic screens, which takes advantage of recent increases in computing power. Applying it to autism, they have uncovered genes that had not been suggested in previous analyses.

By crunching data from the genomes of hundreds of individuals with various degrees of , the researchers identified several functionally related genetic variations that they say are likely to be linked to autism or to the underlying pathology of neuronal development that may cause it.

The work suggests that beginning treatment in infants at the first symptoms, around the age of 12 months, could change the course of the disease. Catching the disorder early, the researchers say, could prevent the permanent "pruning" of neurons, which occurs during the first two years of life, from cementing autistic symptoms in place. The researchers also say that their data-scouring methodology may be used to help identify previously unknown genetic causes of other diseases, even in cases where data has already been exhaustively analyzed.

The research, led by Knut Wittkowski, biostatistician in the Center for Clinical and Translational Science at The Rockefeller University Hospital, is a twist on a traditional data-mining technique known as a genome-wide association study. By comparing DNA from groups of people with a certain illness to those without it, the technique identifies genetic variations that are associated with the disease. Conventional analyses look for individual mutations called SNPs—single-nucleotide polymorphisms. But looking for individual blips in the did not prove a reliable way to identify for early-onset diseases like autism. Wittkowski's method looks not just at individual SNPs, but at combinations of several SNPs—the equivalent of looking at whole words rather than just the single letters that form them.

Wittkowski applied this "multivariate" approach to data from studies of autism as well as studies of childhood absence epilepsy, a condition that turns out to have a similar genetic profile.

First, looking at a study of 185 cases of childhood epilepsy, Wittkowski's team found that mutations in genes that control axonal guidance and calcium signaling—both of which are important early in the developing brain when neurons are forming the appropriate connections—led to increased chances of having the disorder. This prompted the researchers to take a closer look at data from one of the largest studies of autism in the country, containing genome sequences of some 2,700 individuals. By using their more powerful statistical approach, the researchers found clusters of mechanistically related genes where previous studies had merely suggested a few isolated SNPs. Their work implicated the Ras pathway—a calcium-dependent signaling network that spurs neuronal growth—as playing a key role in autism.

If confirmed by clinical research, the data points to the possibility that early pharmaceutical intervention could make a significant difference in the development of the disease."Our results suggest that the drugs currently used to treat childhood epilepsy—ion channel modulators—might have a beneficial effect on individuals with autism, if given at the right time, between 9 and 24 months of age," says Wittkowski.

"The implications of the paper are not restricted to autism," Wittkowski says. "Our approach is likely to 'revive' genome-wide association studies as a strategy to identify and to develop novel treatment options for a wide range of diseases, just as people had hoped for when the genetic code was deciphered a decade ago."

Explore further: Study confirms a gene linked to Asperger Syndrome and empathy

More information: "A novel computational biostatistics approach implies impaired dephosphorylation of growth factor receptors as associated with severity of autism." K M Wittkowski, V. Sonakya, B. Bigio, M. K. Tonn, F. Shic, M. Ascano Jr., C. Nasca and G. Gold-Von Simson. Translational Psychiatry (2014) 4, e354; DOI: 10.1038/tp.2013.124
Published online 28 January 2014

Related Stories

Study confirms a gene linked to Asperger Syndrome and empathy

December 17, 2013
(Medical Xpress)—Scientists have confirmed that variations in a particular gene play a key role in the autism spectrum condition known as Asperger Syndrome. They have also found that variations in the same gene are also ...

Mechanism affecting risk of prostate cancer is found

January 10, 2014
A research group at Biocenter Oulu in Finland has identified a mechanism related to a transcription factor that binds much more strongly onto a particular SNP variant, thereby initiating a genetic programme which enhances ...

Gene family mutation, autism linked

January 28, 2014
(Medical Xpress)—Harvard Medical School researchers at McLean Hospital have found that a gene family linked to autism, EphB, is essential for proper brain wiring during development. The findings suggest that the abnormal ...

18 novel subtype-dependent genetic variants for autism spectrum disorders revealed

April 27, 2011
By dividing individuals with autism spectrum disorders (ASD) into four subtypes according to similarity of symptoms and reanalyzing existing genome-wide genetic data on these individuals vs. controls, researchers at the George ...

Genetic analysis of individuals with autism finds gene deletions

October 3, 2013
Using powerful genetic sequencing technology, a team of investigators, led by researchers at the Icahn School of Medicine at Mount Sinai, scanned the genome of hundreds of individuals, and discovered those diagnosed with ...

Team first to map autism-risk genes by function

November 21, 2013
Pity the poor autism researcher. Recent studies have linked hundreds of gene mutations scattered throughout the brain to increased autism risk. Where do you start?

Recommended for you

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 ...

Females with autism show greater difficulty with day-to-day tasks than male counterparts

July 14, 2017
Women and girls with autism may face greater challenges with real world planning, organization and other daily living skills, according to a study published in the journal Autism Research.

Researchers investigate possible link between carnitine deficiency and autism

July 13, 2017
Researchers are always looking for new clues to the causes of autism, with special emphasis on prevention or treatment. At Baylor College of Medicine, Dr. Arthur Beaudet has been following clinical and genetic clues in patients ...

How children look at mom's face is influenced by genetic factors and altered in autism

July 12, 2017
New research has uncovered compelling evidence that genetics plays a major role in how children look at the world and whether they have a preference for gazing at people's eyes and faces or at objects.

Oxytocin improves social abilities in some kids with autism, study finds

July 10, 2017
Children with autism showed improved social behavior when treated with oxytocin, a hormone linked to social abilities, according to a new study by researchers at the Stanford University School of Medicine. Children with low ...

Possible early diagnosis of autism spectrum disorder

June 29, 2017
Measuring a set of proteins in the blood may enable earlier diagnosis of autism spectrum disorder (ASD), according to a study from the Peter O'Donnell Jr. Brain Institute at UT Southwestern Medical Center.


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.