Genome-wide assessment of Parkinson's disease in a Southern Spanish population.
Neurobiol Aging
; 45: 213.e3-213.e9, 2016 09.
Article
en En
| MEDLINE
| ID: mdl-27393345
ABSTRACT
Here, we set out to study the genetic architecture of Parkinson's disease (PD) through a Genome-Wide Association Study in a Southern Spanish population. About 240 PD cases and 192 controls were genotyped on the NeuroX array. We estimated genetic variation associated with PD risk and age at onset (AAO). Risk profile analyses for PD and AAO were performed using a weighted genetic risk score. Total heritability was estimated by genome-wide complex trait analysis. Rare variants were screened with single-variant and burden tests. We also screened for variation in known PD genes. Finally, we explored runs of homozygosity and structural genomic variations. We replicate PD association (uncorrected p-value < 0.05) at the following loci ACMSD/TMEM163, MAPT, STK39, MIR4697, and SREBF/RAI1. Subjects in the highest genetic risk score quintile showed significantly increased risk of PD versus the lowest quintile (odds ratio = 3.6, p-value < 4e(-7)), but no significant difference in AAO. We found evidence of runs of homozygosity in 2 PD-associated regions one intersecting the HLA-DQB1 gene in 6 patients and 1 control; and another intersecting the GBA-SYT11 gene in PD case. The GBA N370S and the LRRK2 G2019S variants were found in 8 and 7 cases, respectively, replicating previous work. A structural variant was found in 1 case in the PARK2 gene locus. This current work represents a comprehensive assessment at a genome-wide level characterizing a novel population in PD genetics.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Variación Genética
/
Sinaptotagminas
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Estudio de Asociación del Genoma Completo
/
Cadenas beta de HLA-DQ
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Neurobiol Aging
Año:
2016
Tipo del documento:
Article
País de afiliación:
España