Gender Differences in the Prevalence of Parkinson's Disease

Zirra, Alexandra; Rao, Shilpa; Bestwick, Jonathan P.; Rajalingam, Rajasumi; Marras, Connie; Blauwendraat, Cornelis; Mata, Ignacio; Noyce, Alastair J.

doi:10.1002/mdc3.13584

Cited by 23 publications

(16 citation statements)

References 59 publications

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“…Studies have shown that PD affects males more frequently than females, although a recent meta-analysis showed that this difference in prevalence can be lower than expected and is population specific. 3 Biological aging differs distinctly between males and females because of hormonal and immunological changes that females specifically experience, [4][5][6] and this may contribute to the stark differences observed in PD risk, presentation, severity, and treatment success. 7 Even though estrogen is thought to have a protective role in PD risk, [8][9][10] this remains unclear, because multiple studies contradict this hypothesis.…”

Section: Introductionmentioning

confidence: 99%

“…Sex is an important factor, not only in the development but also in the progression of PD. Studies have shown that PD affects males more frequently than females, although a recent meta‐analysis showed that this difference in prevalence can be lower than expected and is population specific 3 . Biological aging differs distinctly between males and females because of hormonal and immunological changes that females specifically experience, 4‐6 and this may contribute to the stark differences observed in PD risk, presentation, severity, and treatment success 7 .…”

Section: Introductionmentioning

confidence: 99%

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X‐Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease

et al. 2023

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BackgroundSex differences in Parkinson's disease (PD) risk are well‐known. However, the role of sex chromosomes in the development and progression of PD is still unclear.ObjectiveThe objective of this study was to perform the first X‐chromosome–wide association study for PD risk in a Latin American cohort.MethodsWe used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X‐chromosome framework specifically designed for admixed populations.ResultsWe identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478–0.77], P = 3.13 × 10−5 replication odds ratio: 0.60 [0.37–0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non‐brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X‐chromosome–wide association study finding (rs28602900), showing that this variant is associated with PD in non‐European populations.ConclusionsOur results reinforce the importance of including X‐chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

X‐Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease

et al. 2023

Self Cite

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“…Sex is an important factor, not only in the development but also in the progression of PD. Studies have shown that PD affects males more frequently than females, although a recent meta-analysis showed that this difference in prevalence can be lower than expected and is population-specific [3]. Biological aging differs distinctly between males and females due to hormonal and immunological changes that females specifically experience [4–6], and this may contribute to the stark differences observed in PD risk, presentation, severity, and treatment success [7].…”

Section: Introductionmentioning

confidence: 99%

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease

Leal

Rao

French-Kwawu

et al. 2023

Preprint

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Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinson's Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 x 10-5; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, including RAB9B, H2BFM, TSMB15B and GLRA4. We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.

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“…In Germany, the number of prevalent PD patients was estimated at 420,000 in 2015 6 . PD incidence increases with age, but stabilizes in the highest ages, and is higher among males 6‐8 …”

Section: Introductionmentioning

confidence: 99%

“…6 PD incidence increases with age, but stabilizes in the highest ages, and is higher among males. [6][7][8] PD is a chronic progressive disease, and is characterized by varying motor symptoms and non-motor symptoms. 2,5,9,10 Parkinson's disease dementia (PDD) as a non-motor manifestation is present in 13% to 85% of PD patients 6,[11][12][13][14][15] and is associated with reduced psychosocial well-being, 16 higher severity of PD, 17 and increased risk of mortality.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Sex‐Specific Survival on the Incidence of Dementia in Parkinson's Disease

Fink,

Dodel,

Georges

et al. 2023

Movement Disorders

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ObjectiveThe aim of our study is to analyze sex‐specific patterns of Parkinson's disease dementia (PDD) incidence. We are investigating the extent to which sex differences in survival after initial Parkinson's disease (PD) diagnosis influence differences in PDD risk among PD patients.MethodsWe used a random sample of German longitudinal health claims data of persons ages 50+ (2004–2019; n = 250,000) and identified new PD cases ages 65+ who were followed‐up for a PDD diagnosis or death between 2006 and 2017. We performed Cox and competing‐risk regression models, with death as competing event, to calculate PDD hazard ratios (HR) adjusted for age at PD onset, PD severity as measured by the modified Hoehn and Yahr (HY) scale, comorbidities, and medications.ResultsOf 2195 new PD cases, 602 people died before PDD and 750 people developed PDD by the end of 2017. The adjusted risk of PDD differs by sex, with men having a higher PDD risk than women. When accounting for death, men and women do not differ in their PDD risk (HR = 1.02, P = 0.770). Sex‐specific analyses showed significant age and severity effects in women (age: HR = 1.05, P < 0.001; HY 3–5 vs. 0–2.5: HR = 1.46, P = 0.011), but not in men.ConclusionOlder age at first PD diagnosis and higher disease severity increase PDD risk, but this association is attenuated for PD men when controlling for death. This implies that the most frail PD men die rapidly before receiving a dementia diagnosis, whereas women with PD survive at higher rates, regardless of their age at onset and disease severity. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Gender Differences in the Prevalence of Parkinson's Disease

Cited by 23 publications

References 59 publications

X‐Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease

X‐Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease

The Impact of Sex‐Specific Survival on the Incidence of Dementia in Parkinson's Disease

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