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Characterizing the Genetic Architecture of Parkinson's Disease in Latinos
Author(s) -
Loesch Douglas P.,
Horimoto Andrea R. V. R.,
Heilbron Karl,
Sarihan Elif I.,
IncaMartinez Miguel,
Mason Emily,
CornejoOlivas Mario,
Torres Luis,
Mazzetti Pilar,
Cosentino Carlos,
SarapuraCastro Elison,
RiveraValdivia Andrea,
Medina Angel C.,
Dieguez Elena,
Raggio Victor,
Lescano Andres,
Tumas Vitor,
Borges Vanderci,
Ferraz Henrique B.,
Rieder Carlos R.,
SchumacherSchuh Artur,
SantosLobato Bruno L.,
VelezPardo Carlos,
JimenezDelRio Marlene,
Lopera Francisco,
Moreno Sonia,
ChanaCuevas Pedro,
Fernandez William,
Arboleda Gonzalo,
Arboleda Humberto,
ArboledaBustos Carlos E.,
Yearout Dora,
Zabetian Cyrus P.,
Can Paul,
Thornton Timothy A.,
O'Connor Timothy D.,
Mata Ignacio F.
Publication year - 2021
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.26153
Subject(s) - genome wide association study , locus (genetics) , genetics , allele , genetic association , genetic architecture , biology , single nucleotide polymorphism , gene , genotype , quantitative trait locus
Objective This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European‐ancestry subjects, and to increase the diversity in PD genome‐wide association (GWAS) data. Methods We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p ‐value <1 × 10 −5 were tested in a replication cohort of 1,234 self‐reported Latino PD cases and 439,522 Latino controls from 23andMe, Inc. We also performed an admixture mapping analysis where local ancestry blocks were tested for association with PD status. Results One locus, SNCA , achieved genome‐wide significance ( p ‐value <5 × 10 −8 ); rs356182 achieved genome‐wide significance in both the discovery and the replication cohorts (discovery, G allele: 1.58 OR, 95% CI 1.35–1.86, p ‐value 2.48 × 10 −8 ; 23andMe, G allele: 1.26 OR, 95% CI 1.16–1.37, p ‐value 4.55 × 10 −8 ). In our admixture mapping analysis, a locus on chromosome 14, containing the gene STXBP6 , achieved significance in a joint test of ancestries and in the Native American single‐ancestry test ( p ‐value <5 × 10 −5 ). A second locus on chromosome 6, containing the gene RPS6KA2 , achieved significance in the African single‐ancestry test ( p ‐value <5 × 10 −5 ). Interpretation This study demonstrated the importance of the SNCA locus for the etiology of PD in Latinos. By leveraging the demographic history of our cohort via admixture mapping, we identified two potential PD risk loci that merit further study. ANN NEUROL 2021;90:353–365