RESEARCH BREAKTHROUGH: TAA Researchers locate genetic risk indicators for TS

Tourette Association of America Researchers Locate Definitive Genetic Centers for Tourette Syndrome and Related Disorders

Data Collected from 2,434 Tourette Cases and More than 4,000 Controls Reveal
the First Statistically Significant Genetic Risk Factors for Tourette Syndrome

~ Findings Published in the June 21st Issue of the Journal Neuron ~

Bayside, New York – June 21, 2017 – Tourette Association of America (TAA), the premier national non-profit organization serving the Tourette Syndrome (TS) and Tic Disorder community, is proud to announce that conclusive findings of TAA-funded research investigating highly complex genetic risk indicators for TS and related disorders were published today in the prestigious scientific journal Neuron. This major research milestone represents a large-scale collaborative effort involving dozens of clinicians, geneticists and advocacy leaders from around the world, and is the first to identify, with genome-wide significance, two definitive genetic defects underlying the development of Tourette Syndrome and related neurological disorders.

Tourette Syndrome is a complex neuropsychiatric disorder characterized by multiple chronic involuntary motor and vocal tics. The disorder affects approximately 1 in 100 school aged children in the United States. Tics typically emerge during childhood and peak in adolescence, with a subsequent reduction in symptoms. Most TS patients present with additional neurodevelopmental conditions such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Tourette is known to be hereditary, but prior to the findings presented in Neuron today, genetic causes have been highly elusive.

The study, which was funded by the Tourette Association of America, the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS), is the largest ever to analyze genetic structural variants or copy-number variants (CNVs) of Tourette. In the study, scientists from the Tourette Syndrome Association International Consortium for Genetics (TSAICG) analyzed and compared the genes of 2,434 individuals with Tourette Syndrome to 4,093 people without the disorder in order to decipher underlying genetic contributors. An overview of the sample selection, quality control, CNV detection and data analysis performed in the study is described in detail in the Neuron publication, which can be viewed online at: http://www.cell.com/neuron/home.

As reported in Neuron, two prominent gene abnormalities have been definitively shown to be present in TS: deletions (or loss of one copy) of the Neurexin-1 gene (NRXN1), and duplications (or an extra copy) of a different gene called Contactin-6 (CNTN6). Approximately one out of every 100 TS cases studied carries one of these copy-number variants, indicating a significant contribution to the genetic architecture of Tourette Syndrome.

“The genetic evidence presented in Neuron represents a major breakthrough in our understanding of how Tourette develops and who is at increased risk for developing the disorder,” said John Miller, President and CEO of Tourette Association of America. “The Tourette Association of America is enormously proud to have been the facilitating partner for this important discovery by the TSAICG consortium. Today, we are one giant step closer to fulfilling our mission to drive improved quality of life for all who are affected by Tourette and other tic disorders through research, support, and awareness.”

This study represents a multi-pronged, large-scale collaborative effort involving clinical and scientific contributions from some of the most prestigious academic medical institutions focused on neuropsychiatric scientific research and discovery today. Co-corresponding authors of the study are Jeremiah M. Scharf, M.D., Ph.D. at Massachusetts General Hospital in Boston, and Giovanni Coppola, M.D. at the UCLA David Geffen School of Medicine in Los Angeles. Alden Huang, also from UCLA was first author for the study. Carol Mathews, M.D., at University of Florida Health and Peristera Paschou, Ph.D. at Purdue University were also lead investigators in this study. For the last five years, Dr. Scharf and Dr. Mathews have also co-chaired the TAA International Consortium for Genetics, where they have led efforts related to funding, coordinating, generating and analyzing data investigated in this study.

“The field of neuropsychiatric genetics has been fraught with inconsistent results for more than 25 years,” said Jeremiah M. Scharf, M.D., Ph.D., at Massachusetts General Hospital, co-corresponding author for the study, and co-director of the TAA Center for Excellence at Massachusetts General. “The challenge of recognizing that TS is not a single gene disorder, and that a stringent statistical certainty is required in order to declare a gene to be significantly associated with TS has been our long-term aim. We believe that what sets our study apart from prior studies is that the two genes we have identified both surpassed this stringent threshold of ‘genome-wide significance,’ and so, represent the first two definitive TS susceptibility genes.”

“Tourette syndrome was noted to be a hereditary disorder since its discovery in the 1800s, but unravelling the genetic basis of the condition has proven to be incredibly challenging. Thus, the findings now of specific genetic alterations in Tourette represent a significant milestone in the history of the disorder and will open new avenues of research into Tic Disorders in the years to come,” said Dr. Kevin St. P. McNaught, former Executive Vice President of Research and Medical Programs at the Tourette Association of America.

Integral to The Tourette Association’s mission to make life better for people with Tourette or Tic Disorders is the commitment to advance scientific research and understanding through the TAA Research Grants and Fellowships Program. Since its inception in 1984, more than $21 million has been awarded to 250 scientists working in basic scientific and clinical TS research. Projects funded by the organization have provided crucial insights into many areas of the disorder. Funding from TAA has also encouraged many investigators to become and/or remain involved in pursuing TS research. Further, numerous studies that received seed funding from TAA have produced results that garnered the interest and investments of larger stakeholders including the National Institutes of Health and private companies. In this way, the investments in researchers made initially by the Tourette Association have been leveraged many times over.

All TS cases and controls for this study were recruited through the Tourette Association of America, the Tourette Syndrome Association International Consortium for Genetics (TSAICG), or through the Gilles de la Tourette Syndrome GWAS Replication Initiative, with additional controls selected from external studies.

About the Tourette Association of America

Founded in 1972, the TAA is dedicated to making life better for all individuals affected by Tourette and Tic Disorders.  The premier nationwide organization serving this community, the Association works to raise awareness, advance research and provide on-going support.  The TAA directs a network of 32 Chapters and support groups across the country.  For more information on Tourette and Tic Disorders, call 1-888-4-TOURET and visit us at tourette.org, and on Facebook, Twitter, Instagram and YouTube.


Members of the Tourette Syndrome Association International Consortium for Genetics (TSAICG) include:

Cathy L. Barr, James R. Batterson, Cheston Berlin, Ruth D. Bruun, Cathy L. Budman, Danielle C. Cath, Sylvain Chouinard, Giovanni Coppola, Nancy J. Cox, Sabrina Darrow, Lea K. Davis, Yves Dion, Nelson B. Freimer, Marco A. Grados, Erica Greenberg, Matthew E. Hirschtritt, Alden Y. Huang, Cornelia Illmann, Robert A. King, Roger Kurlan, James F. Leckman, Gholson J. Lyon, Irene A. Malaty, Carol A. Mathews, William M. McMahon, Benjamin M. Neale, Michael S. Okun, Lisa Osiecki, David L. Pauls, Danielle Posthuma, Vasily Ramensky, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Jeremiah M. Scharf, Harvey S. Singer, Jan Smit, Jae-Hoon Sul, Douglas Woods, Dongmei Yu.