X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.
Mov Disord
; 38(9): 1625-1635, 2023 09.
Article
in En
| MEDLINE
| ID: mdl-37469269
ABSTRACT
BACKGROUND:
Sex 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.OBJECTIVE:
The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort.METHODS:
We 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.RESULTS:
We 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.CONCLUSIONS:
Our 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Parkinson Disease
/
Chromosomes, Human, X
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Mov Disord
Journal subject:
NEUROLOGIA
Year:
2023
Document type:
Article
Affiliation country: