Insights into X-Linked Susceptibility to Parkinson’s Disease in the South African Population
Bibliographic record
Abstract
Abstract X chromosome-wide association studies (XWAS) have successfully identified risk loci on the X chromosome associated with Parkinson’s disease (PD) susceptibility. However, only three such studies have been completed to date. Here, we present the first XWAS using an African cohort, comprising 690 PD cases and 826 controls. We applied an established XWAS workflow to perform male- and female-stratified analyses, as well as a combined meta-analysis. The male-stratified analysis identified five significant variants, including one lead locus (rs200539602), while the female-stratified analysis revealed 29 significant variants and two lead loci (rs2499550 and rs58045540), where rs2499550 is an upstream variant of the protein-coding gene FAAH2 . The remaining female-stratified significant variants are expression quantitative trait loci for SPIN2A, SPIN2B , and SPIN3 , which are highly expressed in the brain and nerve tissues, making them strong candidates for further investigation. One previously reported PD XWAS locus (rs28602900) was also replicated at a significance threshold of 0.05. The meta-analysis identified five variants surpassing chromosome-wide significance, including two lead loci (rs140715059 and rs141026964), the latter has no significant expression quantitative trait locus information but lies closest to the protein-coding gene MAGEC2 , which may warrant further follow-up. None of the meta-analysis signals replicated in prior neurodegenerative disease XWAS. Overall, this study provides novel insights into the contribution of the X chromosome to PD susceptibility and represents the first PD XWAS to include participants of African ancestry, highlighting the importance of extending genetic studies to diverse populations.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".