Understanding the path from genetic changes to Parkinson’s disease opens possibilities for early diagnosis

HOUSTON, TX – Feb. 6, 2026 – A team led by researchers the Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital and Baylor College of Medicine and has uncovered a chain of events that connects genetic alterations, disruptions in lipid metabolism and the manifestation of Parkinson’s disease in patients. The findings, published in the journal Brain, bring forward the possibility of identifying people at risk before symptoms appear and developing strategies to treat the disease rather than manage the symptoms. 

“Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer's disease, affecting more than 10 million people worldwide. We know more than 100 genes that increase the risk of developing the disease but, in most cases, we do not understand how the genetic change leads to the condition,” said corresponding author Dr. Joshua Shulman, investigator and Co-Director of the Duncan NRI and professor of neurology, neuroscience and molecular and human genetics at Baylor. 

Previous studies have shown that many Parkinson’s susceptibility genes participate in lipid metabolism and that disrupting some lipid functions may directly promote brain alterations that have been linked to the disease’s onset and progression.

The researchers focused on a common Parkinson’s risk gene called SPTSSB, which helps regulate the first steps in the synthesis of sphingolipids. The team specifically focused on an SPTSSB variant known as rs1450522, which has been linked to a modest increase in Parkinson’s risk. 

“We studied blood samples of people carrying this genetic variant who were healthy – they did not show any symptoms of the condition, like tremors, limb stiffness, gait and balance problems,” Shulman said. “We found that this risk variant increases the amount of protein SPTSSB produced in the brain, especially in neurons, and the levels of sphingolipids in blood, when compared to individuals not carrying this variant. Out of 62 sphingolipids that we measured, 23% were significantly altered.”

These findings encouraged the team to look deeper to identify biological markers that may mediate the risk of developing the condition. The team systematically analyzed all the metabolites, the products of the body’s metabolism, present in blood in 149 people with Parkinson’s disease and 150 individuals without the condition. 

“We identified multiple other lipids that were altered in patients with Parkinson’s disease. For instance, fatty acids were present at lower levels in patients than in people without the condition. Interestingly, healthy individuals carrying the SPTSSB variant who had higher levels of multiple sphingolipids in blood also had lower levels of certain fatty acids,” Shulman said.

The researchers confirmed these findings using a large dataset of thousands of individuals. A statistical model developed with these data indicated that the SPTSSB gene variant rs1450522 drives increased Parkinson’s risk, higher levels of SPTSSB protein and altered lipid metabolism. This provides for the first time strong evidence supporting that this chain of events connecting genetic changes and alterations on lipid metabolism may cause Parkinson’s disease.

Although the changes in lipids are modest, Shulman explained, “we think they are important primarily because they give us insights into a mechanism, a process that triggers and sustains the condition. Understanding how these lipid metabolic changes set the path to Parkinson’s disease can guide the development of treatments to prevent or delay the onset of symptoms.”
The researchers are further pursuing this promising line of research because it may also lead to the identification of early diagnosis markers that could be detected in a blood test. 

“Currently, early diagnosis remains an unsolved challenge in Parkinson’s research,” Shulman said. “We need sensitive, specific tests that can detect the disease before symptoms appear. By the time patients come to see me because of their symptoms, often their brains are already significantly affected, and we can only treat the symptoms for which we have effective therapies. But we still lack options for early diagnosis or for delaying or preventing this devastating disease.”

For the complete list of contributors and financial support for this work, see the publication.

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Other contributors to this work include:
Ruth B De-Paula , Jonggeol Kim , Herve Rhinn , Hiba Saade , Fatima Chavez , Téah Segura , Maria Valeria Lozano , Michelle Etoundi , Karla Silos , Naomi Kass , Viktoriya Korchina , Harshavardhan Doddapaneni , Eric Venner , Joseph C Masdeu , Valory Pavlik , Melissa M Yu , Chi-Ying R Lin , Joseph Jankovic , Aron S Buchman , Donna Muzny , Richard A Gibbs , Sarah H Elsea , Asa Abeliovich , Peter Lansbury , Nora Vanegas-Arroyave , and Chad A Shaw.

This study was supported by  Huffington Foundation (JMS, CAS), McGee Family Foundation (JMS), Silverstein Foundation for PD with GBA1 (JMS, JK), the Harrison and Nantz Funds from the Houston Methodist Foundation (JCM), the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital (JMS, CAS), and the Effie Marie Caine Endowed Chair for Alzheimer's Research (JMS).

About Texas Children’s 
Texas Children's, a nonprofit health care organization, is committed to creating a healthier future for children and women throughout the global community by leading in patient care, education and research. Consistently ranked as the best children's hospital in Texas and among the top in the nation, Texas Children's has garnered widespread recognition for its expertise and breakthroughs in pediatric and women's health. The system includes the Texas Children's Duncan NRI; the Texas Children's Research Institute; Texas Children's Pavilion for Women, a comprehensive obstetrics/gynecology facility focusing on high-risk births; Texas Children's Hospital West Campus, a community hospital in suburban West Houston; Texas Children's Hospital The Woodlands, the first hospital devoted to children's care for communities north of Houston and Texas Children's Hospital North Austin, the new state-of-the-art facility providing world-class pediatric and maternal care to Austin families. The organization also created Texas Children's Health Plan, the nation's first HMO focused on children; Texas Children's Pediatrics, the largest pediatric primary care network in the country; Texas Children's Urgent Care clinics that specialize in after-hours care tailored specifically for children; and a global health program that is channeling care to children and women all over the world. Texas Children's Hospital is affiliated with Baylor College of Medicine. 

For more information, visit www.texaschildrens.org.