The X Factor: Unlocking the X Chromosome in Latin American populations

Ideas and Inspiration
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Hi there! I recently listened to the episode 124 of the MDS Podcast. In case you didn’t know (I did not know before this episode), MDS Podcast showcases episodes discussing recent advancements in the field, highlighting journal articles and interviews with authors.

This episode featured Dr. Ignacio Mata, Principal Investigator of the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD), who highlighted the importance of studying the X chromosome in genetic association studies, particularly in Parkinson’s research, a research avenue often overlooked due to the complexities associated with the X chromosome.

The LARGE-PD consortium, which has been operating since 2006, focuses on understanding the genetic and environmental components of neurological disorders, particularly in the Latin American populations. The group has made relevant progress since then, spanning to 40 centers across 13 countries in Latin America and the Caribbean, comprising over 6,000 individuals, including Parkinson’s patients and healthy controls.

As the consortium expanded, they conducted the first genome-wide association study (GWAS) in Latin American populations. Even with a small cohort, the study identified synuclein as a top risk gene plus a novel gene associated with Native American ancestry, NRROS, emerged as a potential risk factor for Parkinson’s.

Now, Dr. Mata’s research group, leaded by Dr. Thiago Peixoto Leal, conducted GWAS and X-chromosome association studies to investigate Parkinson’s risk factors in Latin American cohorts

Challenges in studying the X chromosome include differences in dosage, recombination rates, and X-inactivation between males and females, complicated further by the complex genetic ancestry of Latin Americans. Despite these challenges, the researchers innovatively adapted pipelines to conduct X-chromosome association studies and were able to unveil 86 newly associated variants in eight regions of linkage disequilibrium and discuss their gene expression analysis

Furthermore, to validate their findings, they turned to the Bambui Aging cohort study, a vital epidemiological study in Brazil focused on Parkinson’s disease, which provided a crucial replication cohort.

Looking ahead, the researchers emphasized the need to diversify study populations. They also stressed the importance of exploring protein and gene expression models and utilizing IPS cell models to enhance the understanding of Parkinson’s disease in diverse populations.

To the community, some questions!

  1. Have you ever included the X chromosome in genetic studies’ If so, how?
  2. Can you pinpoint other studies about the relevance of studying the X chromosome in PD?
  3. Do you normally listen to podcasts about scientific breakthroughs in the field? Recommend away channels and episodes!
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Hi @paularp, thanks for sharing! I’m loving the media recommendations I’ve seen here in the DCoP as I’m getting to know the PD space. Here is a direct link for those interested in checking out the episode.

Paula, since you gave such great background, I’m wondering if you have been involved in any of these projects, and, either way, what your thoughts are on next steps for the consortium such as tackling the challenge of recruiting representative trial participants for future research?

Wondering if @malasco or @fbriggs have seen this type of focus in AD or MS?

@roopa @vobsese @jjunker, based on where your research is currently based geographically, wondering if you’ve come across any GWAS studies in South Asia/Africa/Europe that have had the type of focus Paula is raising here?

@vobese, I saw that you mentioned podcasts in this discourse thread. Do you have any podcast recommendations pertinent to PD research?

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Hello @paularp! I really liked your post! As for myself, I haven’t included the evaluation of the X chromosome in genetic studies (which is a type of study I’m currently getting to know), however, I deeply value understanding differences in subtypes and symptoms’ expression accross ages and gender subgroups, and this paper explores this important aspect. I think we have a lot of work to do on this topic in order to really achieve our main goal of finally providing real precision medicine to our patients. I really congratulate Ignacio Mata, Tiago and all the others involved in studying this! This work group also has a lot of really cool people!

Unfortunately, I do not listen t scientific podcasts very frequently, however, maybe this is a new habit I need to develop! The only one I’ve listened was the one related to the discovery of SAA as a biomarker for PD.

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Just realized I incorrectly tagged you all, still getting used to Discourse! See below:

Hi @paularp, thanks for sharing! I’m loving the media recommendations I’ve seen here in the DCoP as I’m getting to know the PD space. Here is a direct link for those interested in checking out the episode.

Paula, since you gave such great background, I’m wondering if you have been involved in any of these projects, and, either way, what your thoughts are on next steps for the consortium such as tackling the challenge of recruiting representative trial participants for future research?

Wondering if @malosco or @fbbriggs have seen this type of focus in AD or MS?

@rooparajan @Vidash @johanna.junker, based on where your research is currently based geographically, wondering if you’ve come across any GWAS studies in South Asia/Africa/Europe that have had the type of focus Paula is raising here?

@Vidash , I saw that you mentioned podcasts in this discourse thread . Do you have any podcast recommendations pertinent to PD research?

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