Polygenic risk score for Parkinson's disease and olfaction among middle-aged to older women

Zichun Cao; Dena G Hernandez; Chenxi Li; Joos Berghausen; Zhehui Luo; Hirotaka Iwaki; Aimee A D'Aloisio; Xuemei Huang; Jayant M Pinto; Dale P Sandler; Andrew B Singleton; Honglei Chen

doi:10.1016/j.parkreldis.2023.105815

Polygenic risk score for Parkinson's disease and olfaction among middle-aged to older women

Parkinsonism Relat Disord. 2023 Oct:115:105815. doi: 10.1016/j.parkreldis.2023.105815. Epub 2023 Aug 17.

Authors

Zichun Cao¹, Dena G Hernandez², Chenxi Li³, Joos Berghausen⁴, Zhehui Luo⁵, Hirotaka Iwaki⁶, Aimee A D'Aloisio⁷, Xuemei Huang⁸, Jayant M Pinto⁹, Dale P Sandler¹⁰, Andrew B Singleton¹¹, Honglei Chen¹²

Affiliations

¹ Department of Epidemiology and Biostatistics, Michigan State University College of Human Medicine, East Lansing, MI, USA. Electronic address: zc@msu.edu.
² Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA. Electronic address: hernand@mail.nih.gov.
³ Department of Epidemiology and Biostatistics, Michigan State University College of Human Medicine, East Lansing, MI, USA. Electronic address: cli@msu.edu.
⁴ Department of Pharmacology & Physiology, Georgetown University, Washington D.C., USA. Electronic address: jhb109@georgetown.edu.
⁵ Department of Epidemiology and Biostatistics, Michigan State University College of Human Medicine, East Lansing, MI, USA. Electronic address: zluo@msu.edu.
⁶ Center for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: hirotaka@datatecnica.com.
⁷ Social & Scientific Systems, a DLH Holdings Corporation, Durham, NC, USA. Electronic address: aimee.daloisio@dlhcorp.com.
⁸ Department of Neurology, Pennsylvania State University College of Medicine, Hershey, PA, USA. Electronic address: xuh15@psu.edu.
⁹ Department of Surgery, The University of Chicago, Chicago, IL, USA. Electronic address: jpinto@surgery.bsd.uchicago.edu.
¹⁰ Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address: sandler@niehs.nih.gov.
¹¹ Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA; Center for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: singleta@mail.nih.gov.
¹² Department of Epidemiology and Biostatistics, Michigan State University College of Human Medicine, East Lansing, MI, USA. Electronic address: chenho19@msu.edu.

PMID: 37611509
PMCID: PMC10592043 (available on 2024-10-01)
DOI: 10.1016/j.parkreldis.2023.105815

Abstract

Introduction: Olfactory impairment and Parkinson's disease (PD) may share common genetic and environmental risk factors. This study investigates the association of a PD polygenic risk score (PRS) with olfaction, and whether the associations are modified by environmental exposures of PM_2.5, NO₂, or smoking.

Methods: This analysis included 3358 women (aged 50-80) from the Sister Study with genetic data and results from the Brief Smell Identification Test (B-SIT) administered in 2018-2019. PD PRS was calculated using 90 single nucleotide polymorphisms. Olfactory impairment was defined with different B-SIT cutoffs, and PD diagnosis was adjudicated via expert review. We report odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression.

Results: As expected, PD PRS was strongly associated with the odds of having PD (OR highest vs. lowest quartile = 3.79 (1.64, 8.73)). The highest PRS quartile was also associated with olfactory impairment, with OR ranging from 1.24 (0.98, 1.56) for a B-SIT cutoff of 9 to 1.42 (1.04, 1.92) for a cutoff of 6. For individual B-SIT items, the highest PRS quartile was generally associated with lower odds of correctly identifying the odorant, albeit only statistically significant for pineapple (0.72 (0.56, 0.94), soap (0.76 (0.58, 0.99)) and rose (0.70 (0.54, 0.92)). The association of PD PRS with olfactory impairment was not modified by airborne environmental exposures or smoking.

Conclusion: These preliminary data suggest that high PD genetic susceptibility is associated with olfactory impairment in middle-aged and older women.

Keywords: Genetic susceptibility; Olfactory impairment; Parkinson.

Publication types

Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Female
Humans
Middle Aged
Olfaction Disorders* / genetics
Parkinson Disease* / complications
Parkinson Disease* / epidemiology
Parkinson Disease* / genetics
Risk Factors
Smell / genetics
Smoking

Abstract

Publication types

MeSH terms

Grants and funding