Abstract
Background: The Latino population is greatly understudied in biomedical research, including genetics. Very little information is available on presence of known variants originally identified in non-Hispanic white patients or novel variants in the Latino population. The Latino population is admixed, with contributions of European, African, and Amerindian ancestries. Therefore, the ancestry surrounding a gene (local ancestry, LA) can be any of the three contributing ancestries and thus can determine the presence or risk effect of variants detected.Methods: We sequenced the major exons and exons of reported Latino-specific variants in GBA and LRRK2 and performed genome-wide genotyping for LA assessments in 79 Latino Parkinson disease (PD) patients, of which ~80% identified as Caribbean Latino.Results: We observed five carriers of LRRK2 p.G2019S, one GBA p.T408M, and three GBA p.N409S on European as well as three GBA p.L13R on African LA backgrounds. Previous Latino variant GBA p.K237E was not observed in this dataset. A novel highly conserved and predicted damaging variant LRRK2 p.D734N was identified in two unrelated individuals with African LA. Additionally, we identified rare, functional variants LRRK2 p.P1480L and GBA p.S310G in one individual each heterozygous for European/Amerindian LA.Discussion: Additional functional analysis will be needed to determine the pathogenicity of the novel variants in PD. However, the identification of novel disease variants in the Latino cohort potentially contributing to PD supports to importance of inclusion of Latinos in genetics research to provide insight in PD genetics in Latinos specifically as well as other populations with the same ancestral contributions.
Highlights
Parkinson disease (PD) is the second most common neurodegenerative disease next to Alzheimer disease (AD), affecting individuals of all races and ethnicities
We extended LRRK2’s analyses to all exons coding for functional domains Roc and Kinase, as well as exons harboring putative pathogenic variants identified in NHW patients in-house and by collaborators
We sequenced exons with reported pathogenic or strong risk variants for PD in three known PD genes (LRRK2, GBA, and SNCA) to evaluate presence of these variants originally identified in NHW patients in a Latino cohort enriched for Caribbean patients
Summary
Parkinson disease (PD) is the second most common neurodegenerative disease next to Alzheimer disease (AD), affecting individuals of all races and ethnicities. Most studies of PD, have been conducted in individuals of European (non-Hispanic whites, NHW) and Asian descent. Incidence rates of PD are slightly higher in Latinos than for NHW [1, 2], indicating a clear disregard of the field to include Latinos in PD research. The bias toward NHW leads to health disparities for PD diagnosis and treatment. The health disparities experienced by Latinos are likely understudied and underestimated despite the fact they are the fastest-growing and largest minority in the US (18.3%) [4]. The Latino population is greatly understudied in biomedical research, including genetics. Very little information is available on presence of known variants originally identified in non-Hispanic white patients or novel variants in the Latino population. The Latino population is admixed, with contributions of European, African, and Amerindian ancestries. The ancestry surrounding a gene (local ancestry, LA) can be any of the three contributing ancestries and can determine the presence or risk effect of variants detected
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