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

Gene-Environment Interactions in Progressive Supranuclear Palsy

Irene Litvan  1 , James A Proudfoot  2 , Eden R Martin  3 , David Standaert  4 , David Riley  5 , Deborah Hall  6 , Connie Marras  7 , Ece Bayram  1 , Richard M Dubinsky  8 , Yvette Bordelon  9 , Stephen Reich  10 , David Shprecher  11   12 , Benzi Kluger  13 , Christopher Cunningham  14 , Gerard D Schellenberg  15 , Joseph Jankovic  16
Affiliations

Gene-Environment Interactions in Progressive Supranuclear Palsy

Irene Litvan et al. Front Neurol. .

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.

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Conflict of interest statement

IL supported by the National Institutes of Health grants: 2R01AG038791-06A, U01NS090259, U01NS100610, U01NS80818, R25NS098999, P20GM109025; U19 AG063911-1; 1R21NS114764-01A1; Michael J Fox Foundation, Lewy Body Association, Abbvie, Biogen, Centogene, Roche, EIP-Pharma and Biohaven Pharmaceuticals. She was member of a Lundbeck Advisory Board. She receives her salary from the University of California San Diego and as Chief Editor of Frontiers in Neurology. DSt supported by the Abbvie, Inc., the American Parkinson Disease Association, the Michael J. Fox Foundation for Parkinson Research, Alabama Department of Commerce, the Department of Defense, and NIH grants P50NS108675, R25NS079188, and T32NS095775. He has a clinical practice and is compensated for these activities through the University of Alabama Health Services Foundation. He has served as a consultant for or received honoraria from Abbvie Inc., Sutter Health, the International Parkinson Disease and Movement Disorder Society, Theravance, McGraw Hill, and Sanofi-Aventis. He is a member of the faculty of the University of Alabama at Birmingham and is supported by endowment and University funds. CM received research funding from The Michael J Fox Foundation, Canadian Institutes of Health Research, Parkinson's Foundation (US), International Parkinson and Movement Disorders Society. She is employed by University Health Network, contracted by Grey Matter Technologies, and receives financial compensation as a steering committee member from the Michael J Fox Foundation. DSh employed by Banner Health, received research support from the Arizona Alzheimer's Consortium, Abbvie, Acadia, Aptinyx, Axovant, Biogen, Eisai, Eli Lilly, Enterin, Neurocrine, Michael J Fox Foundation, NIH, Nuvelution, Theravance and Teva; consultant fees from Amneal, Forensis and Neurocrine; speaker honoraria from Acorda, Neurocrine, Sunovion, Teva and US World Meds. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Number of participants at each stage of the study. From an initial sample of 442, 139 were excluded due to either incompatible diagnoses, too advanced disease, dropping out, or incomplete data. An additional 11 were excluded due to inability to match for race with a control. 292 final cases were matched with either their original control 1 (non-blood relative), a different case's control 1, or a different case's control 2 (spouse or caretaker).
Figure 2
Figure 2
Association between age of PSP symptom onset and the interaction of MAPTrs242557 and years of living within 1 mile of agriculture. A is the minor allele, G is the major allele for MAPTrs242557; G/G corresponds to 0 minor allele, A/G corresponds to 1 minor allele, and A/A corresponds to 2 minor alleles.
Figure 3
Figure 3
Association between age of PSP symptom onset and the interaction of STX6rs1411478 and exposure to organic solvents. A is the minor allele, G is the major allele for STX6rs1411478; G/G corresponds to 0 minor allele, A/G corresponds to 1 minor allele, A/A corresponds to 2 minor alleles.
See this image and copyright information in PMC

References

    1. Schrag A, Ben-Shlomo Y, Quinn NP. Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study. Lancet. (1999) 354:1771–5. 10.1016/S0140-6736(99)04137-9 - DOI - PubMed
    1. Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, et al. . Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. (1996) 47:1–9. 10.1212/WNL.47.1.1 - DOI - PubMed
    1. Chiu WZ, Kaat LD, Seelaar H, Rosso SM, Boon AJW, Kamphorst W, et al. . Survival in progressive supranuclear palsy and frontotemporal dementia. J Neurol Neurosurg Psychiatry. (2010) 81:441–5. 10.1136/jnnp.2009.195719 - DOI - PubMed
    1. Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain. (2007) 130:1552–65. 10.1093/brain/awm032 - DOI - PubMed
    1. Nath U, Ben-Shlomo Y, Thomson RG, Morris HR, Wood NW, Lees AJ, et al. . The prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK. Brain. (2001) 124:1438–49. 10.1093/brain/124.7.1438 - DOI - PubMed