Gene-Environment Interactions in Progressive Supranuclear Palsy

Irene Litvan; James A Proudfoot; Eden R Martin; David Standaert; David Riley; Deborah Hall; Connie Marras; Ece Bayram; Richard M Dubinsky; Yvette Bordelon; Stephen Reich; David Shprecher; Benzi Kluger; Christopher Cunningham; Gerard D Schellenberg; Joseph Jankovic

doi:10.3389/fneur.2021.664796

Gene-Environment Interactions in Progressive Supranuclear Palsy

Front Neurol. 2021 Apr 9:12:664796. doi: 10.3389/fneur.2021.664796. eCollection 2021.

Authors

Irene Litvan¹, James A Proudfoot², Eden R Martin³, David Standaert⁴, David Riley⁵, Deborah Hall⁶, Connie Marras⁷, Ece Bayram¹, Richard M Dubinsky⁸, Yvette Bordelon⁹, Stephen Reich¹⁰, David Shprecher^{11

12}, Benzi Kluger¹³, Christopher Cunningham¹⁴, Gerard D Schellenberg¹⁵, Joseph Jankovic¹⁶

Affiliations

¹ Department of Neurosciences, Parkinson and Other Movement Disorders Center, University of California, San Diego, La Jolla, CA, United States.
² Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA, United States.
³ John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, United States.
⁴ Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States.
⁵ InMotion, Warrensville Heights, OH, United States.
⁶ Department of Neurological Sciences, Rush University, Chicago, IL, United States.
⁷ Morto and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Research, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
⁸ Department of General Neurology, University of Kansas Medical Center, Kansas City, KS, United States.
⁹ Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.
¹⁰ Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, United States.
¹¹ Banner Sun Health Research Institute, Sun City, AZ, United States.
¹² Department of Neurology, University of Utah, Salt City, UT, United States.
¹³ Department of Neurology, University of Colorado, Denver, CO, United States.
¹⁴ Division of Movement Disorders, Department of Neurology, University of Louisville School of Medicine, Louisville, KY, United States.
¹⁵ Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.
¹⁶ Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, United States.

Abstract

Several genetic and environmental factors have been reported in progressive supranuclear palsy (PSP), although none were identified as a definitive cause. We aimed to explore potential gene-environment interactions in PSP. Two hundred and ninety two PSP cases and 292 controls matched for age, sex, and race from the ENGENE-PSP were analyzed to determine the association between PSP and minor alleles of 5 single nucleotide polymorphisms (SNPs) in 4 genes (MAPT, MOBP, EIF2AK3, and STX6), which were previously associated with PSP risk. Interactions between these SNPs and environmental factors, including previously reported occupational and agricultural risk factors for PSP, were assessed for PSP odds and age of symptom onset. Minor alleles of MAPTrs242557 and EIF2AK3rs7571971 were individually associated with increased odds; MAPTrs8070723 minor alleles were associated with lower PSP odds. There were several gene-environment interactions for PSP odds and age of symptom onset, however, they did not remain significant after FDR-correction. Larger scale studies are required to determine potential interactions.

Keywords: environment; epidemiology; gene; progressive supranuclear palsy; risk factors.

Grants and funding

R01 AG024040/AG/NIA NIH HHS/United States