scholarly journals Characterizing the Genetic Architecture of Parkinson's Disease in Latinos

2021 ◽  
Author(s):  
Douglas P. Loesch ◽  
Andrea R. V. R. Horimoto ◽  
Karl Heilbron ◽  
Elif Irem Sarihan ◽  
Miguel Inca‐Martinez ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Architecture

scholarly journals Characterizing the genetic architecture of Parkinson’s disease in Latinos

2020 ◽  
Author(s):  
Douglas Loesch ◽  
Andrea R. V. R. Horimoto ◽  
Karl Heilbron ◽  
Elif Irem Sarihan ◽  
Miguel Inca-Martinez ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Native American ◽  
Genetic Architecture ◽  
Association Studies ◽  
African Ancestry ◽  
Population History ◽  
Genome Wide Association Studies ◽  
Association Testing ◽  
Significant Locus

AbstractTo date, over 90 Parkinson’s disease (PD) risk variants have been reported from genome-wide association studies (GWAS). However, these GWAS efforts have been limited to individuals of European and East Asian ancestry. We performed the first GWAS of Latino PD patients from South America, comparing 807 cases against 690 controls followed by association testing of suggestive loci in a replication cohort of 1,234 cases and 439,522 controls. We demonstrated that SNCA plays a significant role in PD etiology in a Latino cohort and identified a suggestive locus near NRROS on chromosome 3 that appeared to be driven by Peruvian subjects. We also characterized the overlap of PD genetic architecture between Europeans and Latinos with a replication of significant variants identified by Nalls et al. in their 2019 GWAS1, finding 80% concordance in direction of effect. We then leveraged the population history of Latinos via admixture mapping, identifying a significant locus on chromosome 14 in a joint test of ancestries, driven by the Native American ancestral background, and a significant locus on chromosome 6 in our test of African ancestry, containing the genes STXBP6 and RPS6KA2, respectively. Ultimately, our work reflects the most comprehensive characterization of PD genetic architecture in Latinos to date.

The genetic architecture of Parkinson's disease

2020 ◽  
Vol 19 (2) ◽  
pp. 170-178 ◽  
Author(s):  
Cornelis Blauwendraat ◽  
Mike A Nalls ◽  
Andrew B Singleton
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Architecture

scholarly journals Exploring the Genetic Architecture of Parkinson's Disease in a Southern Spanish Population

2017 ◽  
Vol 07 (04) ◽  
Author(s):  
Sara Bandres Ciga ◽  
Clara Ruz ◽  
Francisco J Barrero ◽  
Francisco Escamilla Sevilla ◽  
Javier Pelegrina ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Architecture ◽  
Spanish Population

scholarly journals Genetic correlation and causality of cancers and Parkinson’s disease

2020 ◽  
Author(s):  
Konstantin Senkevich ◽  
Sara Bandres-Ciga ◽  
Eric Yu ◽  
Upekha E. Liyanage ◽  
Alastair J Noyce ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Correlation ◽  
Causal Relationship ◽  
Genetic Architecture ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Shared Genetic

AbstractBackground and objectivesMost cancers appear with reduced frequency in Parkinson’s disease (PD), but the prevalence of melanoma and brain cancers are often reported to be increased. Shared genetic architecture and causal relationships to explain these associations have not been fully explored.MethodsLinkage disequilibrium score regression (LDSC) was applied for five cancer studies with available genome-wide association studies (GWAS) summary statistics to examine genetic correlations with PD. Additionally, we used GWAS summary statistics of 15 different types of cancers as exposures and two-sample Mendelian randomization to study the causal relationship with PD (outcome).ResultsLDSC analysis revealed a potential genetic correlation between PD and melanoma, breast cancer and prostate cancer. There was no evidence to support a causal relationship between the studied cancers and PD.ConclusionsOur results suggest shared genetic architecture between PD and melanoma, breast, and prostate cancers, but no obvious causal relationship between cancers and PD.

scholarly journals Mapping the Diverse and Inclusive Future of Parkinson’s Disease Genetics and Its Widespread Impact

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1681
Author(s):  
Inas Elsayed ◽  
Alejandro Martinez-Carrasco ◽  
Mario Cornejo-Olivas ◽  
Sara Bandres-Ciga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Architecture ◽  
European Ancestry ◽  
Genetic Studies ◽  
New Era ◽  
Genetics Research ◽  
The Impact ◽  
Insight Into ◽  
Testing And Counseling

Over the last decades, genetics has been the engine that has pushed us along on our voyage to understand the etiology of Parkinson’s disease (PD). Although a large number of risk loci and causative mutations for PD have been identified, it is clear that much more needs to be done to solve the missing heritability mystery. Despite remarkable efforts, as a field, we have failed in terms of diversity and inclusivity. The vast majority of genetic studies in PD have focused on individuals of European ancestry, leading to a gap of knowledge on the existing genetic differences across populations and PD as a whole. As we move forward, shedding light on the genetic architecture contributing to PD in non-European populations is essential, and will provide novel insight into the generalized genetic map of the disease. In this review, we discuss how better representation of understudied ancestral groups in PD genetics research requires addressing and resolving all the challenges that hinder the inclusion of these populations. We further provide an overview of PD genetics in the clinics, covering the current challenges and limitations of genetic testing and counseling. Finally, we describe the impact of worldwide collaborative initiatives in the field, shaping the future of the new era of PD genetics as we advance in our understanding of the genetic architecture of PD.

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