Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients

Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)‡

doi:10.1002/mds.28353

Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients

Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)‡

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Background: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. Methods: We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. Results: Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69–10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10⁻⁷). Conclusions: We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population.

Original language	English
Pages (from-to)	434-441
Number of pages	8
Journal	Movement Disorders
Volume	36
Issue number	2
DOIs	https://doi.org/10.1002/mds.28353
State	Published - Feb 2021

Bibliographical note

Funding Information:
: Recruitment of LARGE‐PD participants was funded by an International Research Program Grant from the Parkinson's Disease Foundation (2010‐2012), and this work was funded by a Stanley Fahn Junior Faculty Award from the Parkinson's Foundation. This work was also supported by a research grant from the American Parkinson's Disease Association, with resources and the use of facilities at the Veterans Affairs Puget Sound Health Care System. M. J. ‐D. ‐R. and C. V. ‐P. were supported by the Committee for Development and Research (Comite para el desarrollo y la investigación‐CODI)‐Universidad de Antioquia grant 2020‐31455. Funding agencies

Funding Information:
Dr. Horimoto is supported by grants from the Parkinson's Disease Foundation. Dr. Lescano is supported by grants from the Parkinson's Disease Foundation. Dr. Borges reports honoraria from ACHÉ Laboratorios Farmacéuticos. Dr. Rieder reports financial support provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil). Dr. Velez‐Pardo and Dr. Jimenez‐Del‐Rio are supported by a CODI grant. Ms. Yearout is supported by grants from American Parkinson's Disease Association, Parkinson's Disease Foundation for this research, as well as grants from Department of Veterans Affairs, NINDS, National Institutes of Health, Michael J. Fox Foundation unrelated to this research. Dr. Zabetian is supported by grants from Parkinson's Foundation and salary from the Department of Veterans Affairs for this research, as well as grants from the National Institutes of Health, Department of Veterans Affairs, and American Parkinson Disease Association unrelated to this research. Dr. Thornton is supported by grants from Parkinson's Disease Foundation. Dr. O’Connor is supported by grants from the National Institutes of Health. Dr. Mata is supported by grants from the Department of Veterans Affairs, Parkinson's Foundation, American Parkinson's Disease Association, Michael J. Fox Foundation, and National Institutes of Health.

Publisher Copyright:
© 2020 International Parkinson and Movement Disorder Society

Keywords

Latin America
Parkinson's disease
copy number variants
genetics

Access to Document

10.1002/mds.28353

Cite this

@article{f16ca5a1fba1450f8c29903d5d9efcd9,

title = "Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients",

abstract = "Background: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. Methods: We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. Results: Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69–10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10−7). Conclusions: We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population.",

keywords = "Latin America, Parkinson's disease, copy number variants, genetics",

author = "{Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)‡} and Sarihan, {Elif Irem} and Eduardo P{\'e}rez-Palma and Niestroj, {Lisa Marie} and Douglas Loesch and Miguel Inca-Martinez and Horimoto, {Andrea R.V.R.} and Mario Cornejo-Olivas and Luis Torres and Pilar Mazzetti and Carlos Cosentino and Elison Sarapura-Castro and Andrea Rivera-Valdivia and Elena Dieguez and Victor Raggio and Andres Lescano and Vitor Tumas and Vanderci Borges and Ferraz, {Henrique B.} and Rieder, {Carlos R.} and Schumacher-Schuh, {Artur F.} and Santos-Lobato, {Bruno L.} and Carlos Velez-Pardo and Marlene Jimenez-Del-Rio and Francisco Lopera and Sonia Moreno and Pedro Chana-Cuevas and William Fernandez and Gonzalo Arboleda and Humberto Arboleda and Arboleda-Bustos, {Carlos E.} and Dora Yearout and Zabetian, {Cyrus P.} and Thornton, {Timothy A.} and O'Connor, {Timothy D.} and Dennis Lal and Mata, {Ignacio F.} and Federico Micheli and Emilia Gatto and Vitor Tumas and Vanderci Borges and Ferraz, {Henrique B.} and Rieder, {Carlos R.M.} and Artur Shumacher-Schuh and Santos-Lobato, {Bruno L.} and Pedro Chan{\'a} and Carlos Velez-Pardo and Marlene Jimenez-Del-Rio and Francisco Lopera and Gonzalo Arboleda and {Mazzetti Soler}, {Pilar Elena}",

note = "Publisher Copyright: {\textcopyright} 2020 International Parkinson and Movement Disorder Society",

year = "2021",

month = feb,

doi = "10.1002/mds.28353",

language = "Ingl{\'e}s",

volume = "36",

pages = "434--441",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley and Sons Inc.",

number = "2",

}

TY - JOUR

T1 - Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients

AU - Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)‡

AU - Sarihan, Elif Irem

AU - Pérez-Palma, Eduardo

AU - Niestroj, Lisa Marie

AU - Loesch, Douglas

AU - Inca-Martinez, Miguel

AU - Horimoto, Andrea R.V.R.

AU - Cornejo-Olivas, Mario

AU - Torres, Luis

AU - Mazzetti, Pilar

AU - Cosentino, Carlos

AU - Sarapura-Castro, Elison

AU - Rivera-Valdivia, Andrea

AU - Dieguez, Elena

AU - Raggio, Victor

AU - Lescano, Andres

AU - Tumas, Vitor

AU - Borges, Vanderci

AU - Ferraz, Henrique B.

AU - Rieder, Carlos R.

AU - Schumacher-Schuh, Artur F.

AU - Santos-Lobato, Bruno L.

AU - Velez-Pardo, Carlos

AU - Jimenez-Del-Rio, Marlene

AU - Lopera, Francisco

AU - Moreno, Sonia

AU - Chana-Cuevas, Pedro

AU - Fernandez, William

AU - Arboleda, Gonzalo

AU - Arboleda, Humberto

AU - Arboleda-Bustos, Carlos E.

AU - Yearout, Dora

AU - Zabetian, Cyrus P.

AU - Thornton, Timothy A.

AU - O'Connor, Timothy D.

AU - Lal, Dennis

AU - Mata, Ignacio F.

AU - Micheli, Federico

AU - Gatto, Emilia

AU - Tumas, Vitor

AU - Borges, Vanderci

AU - Ferraz, Henrique B.

AU - Rieder, Carlos R.M.

AU - Shumacher-Schuh, Artur

AU - Santos-Lobato, Bruno L.

AU - Chaná, Pedro

AU - Velez-Pardo, Carlos

AU - Jimenez-Del-Rio, Marlene

AU - Lopera, Francisco

AU - Arboleda, Gonzalo

AU - Mazzetti Soler, Pilar Elena

PY - 2021/2

Y1 - 2021/2

N2 - Background: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. Methods: We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. Results: Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69–10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10−7). Conclusions: We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population.

AB - Background: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. Methods: We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. Results: Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69–10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10−7). Conclusions: We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population.

KW - Latin America

KW - Parkinson's disease

KW - copy number variants

KW - genetics

UR - http://www.scopus.com/inward/record.url?scp=85096643729&partnerID=8YFLogxK

U2 - 10.1002/mds.28353

DO - 10.1002/mds.28353

M3 - Artículo

C2 - 33150996

AN - SCOPUS:85096643729

SN - 0885-3185

VL - 36

SP - 434

EP - 441

JO - Movement Disorders

JF - Movement Disorders

IS - 2

ER -

Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this