March 1, 2019
Study finds gene associated with higher risk of Tourette syndrome
WEST LAFAYETTE, Ind. — Tourette syndrome, although not life-threatening, can have serious impacts on the lives of those affected. As many as 1 percent of all children between the ages of 5 and 17 in the U.S. are affected by Tic disorders, but no medications exist that completely eradicate symptoms.
Researchers know Tourette syndrome is inherited, but genetically, it is extremely complex. The condition is polygenic, which means it’s controlled by two or more genes (usually several), at different places on different chromosomes. This is why a large group of international researchers has come together to pursue the largest genome-wide scan for Tourette syndrome to date.
“Our goal was to identify genetic variants that are common in the population and increase the risk for onset of symptoms,” said Peristera Paschou, an associate professor of biological sciences at Purdue University.
By analyzing a sample of nearly 5,000 patients with Tourette syndrome and 9,500 controls, the researchers found a genetic variant on chromosome 13 associated with a higher risk for the disease. The findings were published in The American Journal of Psychiatry.
“Using information from the entire genome, we were able to construct polygenic risk scores that predicted Tourette syndrome severity,” Paschou said. “These can be used to simultaneously consider risk conferred by multiple genes throughout the genome. The results validate the highly polygenic nature of Tourette syndrome and provide a genomic profile that is associated with more severe symptoms in patients.”
Determining the genetic architecture of the disease is key to treating and preventing it. But the pattern of inheritance is complex; there could be a few genes with substantial effects, or many genes with smaller effects and environmental factors could play a role.
A future collaborative study between Purdue, Massachusetts General Hospital and the University of Florida will analyze an even larger sample of nearly 12,000 patients.
“Our ultimate goal is to help guide future drug development and clinical trials for Tourette syndrome,” Paschou said.
The work aligns with Purdue's Giant Leaps celebration, acknowledging the university’s global advancements made in health, longevity and quality of life as part of Purdue’s 150th anniversary. This is one of the four themes of the yearlong celebration’s Ideas Festival, designed to showcase Purdue as an intellectual center solving real-world issues.
Writer: Kayla Zacharias, 765-494-9318, email@example.com
Source: Peristera Paschou, 765-494-1601, firstname.lastname@example.org
Note to Journalists: For a copy of the paper, please contact Kayla Zacharias, Purdue News Service, email@example.com.
Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies
Dongmei Yu, M.S., Jae Hoon Sul, Ph.D., Fotis Tsetsos, Ph.D., Muhammad S. Nawaz, Ph.D., Alden Y. Huang, Ph.D., Ivette Zelaya, Ph.D., Cornelia Illmann, Ph.D., Lisa Osiecki, B.A., Sabrina M. Darrow, Ph.D., Matthew E. Hirschtritt, M.D., M.P.H., Erica Greenberg, M.D., Kirsten R. Muller-Vahl, M.D., Manfred Stuhrmann, M.D., Yves Dion, M.D., Guy Rouleau, M.D., Harald Aschauer, M.D., Mara Stamenkovic, M.D., Monika Schlögelhofer, M.A., Paul Sandor, M.D., Cathy L. Barr, Ph.D., Marco Grados, M.D., M.P.H., Harvey S. Singer, M.D., Markus M. Nöthen, M.D., Johannes Hebebrand, M.D., Anke Hinney, Ph.D., Robert A. King, M.D.,
Thomas V. Fernandez, M.D., Ph.D., Csaba Barta, Ph.D., Zsanett Tarnok, Ph.D., Peter Nagy, M.D., Christel Depienne, Ph.D., Yulia Worbe, M.D., Ph.D., Andreas Hartmann, M.D., Cathy L. Budman, M.D., Renata Rizzo, M.D., Ph.D., Gholson J. Lyon, M.D., Ph.D., William M. McMahon, M.D., James R. Batterson, M.D., Danielle C. Cath, M.D., Irene A. Malaty, M.D., Michael S. Okun, M.D., Cheston Berlin, M.D., Douglas W. Woods, Ph.D., Paul C. Lee, M.D., M.P.H., Joseph Jankovic, M.D., Mary M. Robertson, M.D., Ph.D., Donald L. Gilbert, M.D., Lawrence W. Brown, M.D., Barbara J. Coffey, M.D., Andrea Dietrich, Ph.D., Pieter J. Hoekstra, M.D., Ph.D., Samuel Kuperman, M.D., Samuel H. Zinner, M.D., Pétur Luðvigsson, M.D., Evald Sæmundsen, M.D., Ólafur Thorarensen, M.D., Gil Atzmon, Ph.D., Nir Barzilai, M.D., Michael Wagner, Ph.D., Rainald Moessner, M.D., Roel Ophoff, Ph.D., Carlos N. Pato, M.D., Ph.D., Michele T. Pato, M.D., James A. Knowles, M.D., Ph.D., Joshua L. Roffman, M.D., Jordan W. Smoller, M.D., Sc.D., Randy L. Buckner, Ph.D., A. Jeremy Willsey, Ph.D., Jay A. Tischfield, Ph.D., Gary A. Heiman, Ph.D., Hreinn Stefansson, Ph.D., Kári Stefansson, M.D., Danielle Posthuma, Ph.D., Nancy J. Cox, Ph.D., David L. Pauls, Ph.D., Nelson B. Freimer, M.D., Benjamin M. Neale, Ph.D., Lea K. Davis, Ph.D., Peristera Paschou, Ph.D., Giovanni Coppola, M.D., Carol A. Mathews, M.D., Jeremiah M. Scharf, M.D., Ph.D., on behalf of the Tourette Association of America International Consortium for Genetics, the Gilles de la Tourette GWAS Replication Initiative, the Tourette International Collaborative Genetics Study, and the Psychiatric Genomics Consortium Tourette Syndrome Working Group
Modulation of gene expression through non- coding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette’s syn- drome pathogenesis. At a genetic level, tic disorders re- present a continuous spectrum of disease, supporting the unification of Tourette’s syndrome and other tic disorders in future diagnostic schemata. Tourette’s PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disor- ders, as well as tic persistence and lifetime tic severity.