Category: Parkinson's Disease: Genetics
Objective: To assess the association between Sex Hormone Binding Globulin (SHBG), Testosterone, and Estradiol with Parkinson’s disease (PD).
Background: Sex hormones may protect dopaminergic neurons, possibly preventing or delaying the onset of Parkinson’s disease (PD). However, studies of PD based on reproductive characteristics have been inconclusive.
Method: We performed inverse-variance weighting (IVW) MR analysis using external GWAS summary data (UK biobank) to estimate the effects of genetic variants on measured sex hormone levels, stratified by sex. The associations between genetic variants and PD were estimated in two population-based studies (PASIDA, Denmark, and PEG, USA) that enrolled 1,737 females (825 PD, 912 controls), and 2,430 males (1,218 PD, 1,212 controls) of European ancestry. We included independent variants (linkage disequilibrium R2<0.1) and a P-value of 5×10-8 in the GWAS for sex hormones. Sensitivity analyses included using alternate MR techniques and varying the P-value thresholds.
Results: There were no statistically significant findings among males. Among females, per 10 pmol/L increase in estimated SHBG concentration increased the PD risk by 19% (OR: 1.19; 95%CI: 1.10 to 1.30, P: 6.7 x 10-5). Results were consistent using a weighted median MR analysis and also with varying P-value thresholds except with MR-Egger. The original testosterone instrument was not associated with PD status but when we restricted to the 12 strongest independent SNPs (P<1 x10-20), a negative association emerged between estimated testosterone level and PD status among women using both MR-Egger and weighted median MR.
Conclusion: No effects of sex hormones on PD status were identified among males. Higher estimated SHBG concentrations, and possibly decreasing testosterone concentration, were associated with an increased risk of PD among women. We did not find an association between estradiol and PD status; however, this could be due to a weaker instrument for estradiol. Our preliminary findings indicate that sex hormones may influence PD risk among women, further supporting the hypothesis that sex hormones may be neuroprotective.
To cite this abstract in AMA style:
C. Kusters, K. Paul, A. Duarte Folle, A. Keener, J. Bronstein, L. Bertram, J. Hansen, S. Horvath, J. Sinsheimer, C. Lill, B. Ritz. SHBG, and possibly testosterone, are associated with the risk for Parkinson’s disease among women: a Mendelian randomization approach [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/shbg-and-possibly-testosterone-are-associated-with-the-risk-for-parkinsons-disease-among-women-a-mendelian-randomization-approach/. Accessed May 16, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/shbg-and-possibly-testosterone-are-associated-with-the-risk-for-parkinsons-disease-among-women-a-mendelian-randomization-approach/