. 2021 Oct;36(10):2264-2272.

doi: 10.1002/mds.28760. Epub 2021 Aug 23.

Increased Menopausal Age Reduces the Risk of Parkinson's Disease: A Mendelian Randomization Approach

Cynthia D J Kusters¹, Kimberly C Paul², Aline Duarte Folle³, Adrienne M Keener^{2

4}, Jeff M Bronstein^{2

5}, Lars Bertram^{6

7}, Johnni Hansen⁸, Steve Horvath^{1

9}, Janet S Sinsheimer^{1

9

10}, Christina M Lill^{11

12}, Beate R Ritz^{2

3

13}

Affiliations

¹ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
² Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
³ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, California, USA.
⁴ Parkinson's Disease Research, Education, and Clinical Center, Greater Los Angeles Veterans Affairs Medical Center, Los Angeles, California, USA.
⁵ Brain Research Institute, University of California, Los Angeles, California, USA.
⁶ Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
⁷ Department of Psychology, Centre for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway.
⁸ Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
⁹ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, California, USA.
¹⁰ Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
¹¹ Translational Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
¹² Ageing Epidemiology Research Unit, School of Public Health, Imperial College, London, United Kingdom.
¹³ Department of Environmental Health, Fielding School of Public Health, University of California, Los Angeles, California, USA.

PMID: 34426982
PMCID: PMC8530889
DOI: 10.1002/mds.28760

Increased Menopausal Age Reduces the Risk of Parkinson's Disease: A Mendelian Randomization Approach

Cynthia D J Kusters et al. Mov Disord. 2021 Oct.

. 2021 Oct;36(10):2264-2272.

doi: 10.1002/mds.28760. Epub 2021 Aug 23.

Authors

Affiliations

¹ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
² Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
³ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, California, USA.
⁴ Parkinson's Disease Research, Education, and Clinical Center, Greater Los Angeles Veterans Affairs Medical Center, Los Angeles, California, USA.
⁵ Brain Research Institute, University of California, Los Angeles, California, USA.
⁶ Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
⁷ Department of Psychology, Centre for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway.
⁸ Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
⁹ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, California, USA.
¹⁰ Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
¹¹ Translational Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
¹² Ageing Epidemiology Research Unit, School of Public Health, Imperial College, London, United Kingdom.
¹³ Department of Environmental Health, Fielding School of Public Health, University of California, Los Angeles, California, USA.

PMID: 34426982
PMCID: PMC8530889
DOI: 10.1002/mds.28760

Erratum in

Erratum to "Increased Menopausal Age Reduces the Risk of Parkinson's Disease: A Mendelian Approach".
Kusters CDJ, Paul KC, Duarte Folle A, Keener AM, Bronstein JM, Bertram L, Hansen J, Horvath S, Sinsheimer JS, Lill CM, Ritz BR. Kusters CDJ, et al. Mov Disord. 2022 Jun;37(6):1282-1283. doi: 10.1002/mds.28974. Epub 2022 Mar 4. Mov Disord. 2022. PMID: 35245402 Free PMC article. No abstract available.

Abstract

Background: Studies of Parkinson's disease (PD) and the association with age at menarche or menopause have reported inconsistent findings. Mendelian randomization (MR) may address measurement errors because of difficulties accurately reporting the age these life events occur.

Objective: We used MR to assess the association between age at menopause and age at menarche with PD risk.

Methods: We performed inverse variant-weighted (IVW) MR analysis using external genome-wide association study (GWAS) summary data from the United Kingdom biobank, and the effect estimates between genetic variants and PD among two population-based studies (Parkinson's disease in Denmark (PASIDA) study, Denmark, and Parkinson's Environment and Gene study [PEG], United States) that enrolled 1737 female and 2430 male subjects of European ancestry. We, then, replicated our findings for age at menopause using summary statistics from the PD consortium (19 773 women), followed by a meta-analysis combining all summary statistics.

Results: For each year increase in age at menopause, the risk for PD decreased (odds ration [OR], 0.84; 95% confidence interval [CI], 0.73-0.98; P = 0.03) among women in our study, whereas there was no association among men (OR, 0.98; 95% CI, 0.85-1.11; P = 0.71). A replication using summary statistics from the PD consortium estimated an OR of 0.94 (95% CI, 0.90-0.99; P = 0.01), and we calculated a meta-analytic OR of 0.93 (95% CI, 0.89-0.98; P = 0.003). There was no indication for an association between age at menarche and PD (OR, 0.75; 95% CI, 0.44-1.29; P = 0.29).

Conclusions: A later age at menopause was associated with a decreased risk of PD in women, supporting the hypothesis that sex hormones or other factors related to late menopause may be neuroprotective in PD. © 2021 International Parkinson and Movement Disorder Society.

Keywords: Mendelian randomization; Parkinson's disease; females; menarche; menopause.

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Conflict of interest statement

Financial disclosure: No conflicts of interest

Figures

**Figure 1.**
Visual representation of Mendelian Randomization analysis for age at menopause and PD status among women for the top eight independent SNPs based on the combined summary statistics for PD (using the consortium and the PEG&PASIDA study).

**Figure 2.**
Forest plot for the associations between age at menopause and PD status among women for the top eight independent SNPs that were genome-wide statistically significantly associated with age at menopause in the UKBB, using the combined summary statistics for PD (using the consortium and the PEG&PASIDA study).

See this image and copyright information in PMC

References

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Increased Menopausal Age Reduces the Risk of Parkinson's Disease: A Mendelian Randomization Approach

Affiliations

Increased Menopausal Age Reduces the Risk of Parkinson's Disease: A Mendelian Randomization Approach

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical