Genome Wide assessment of Parkinson’s disease in a Southern Spanish population

• Published in: Neurobiology of aging Vol. 45; pp. 213.e3 - 213.e9
• Main Authors: Bandrés-Ciga, S, Price, T.R, Barrero, F.J, Escamilla-Sevilla, F, Pelegrina, J, Arepalli, S, Hernández, D, Gutiérrez, B, Cervilla, J, Rivera, M, Rivera, A.M, Ding, J, Vives, F, Nalls, M.A, Singleton, A.B, Durán, R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2016
• Subjects: Age of Onset; Aged; Female; Genetic Variation; Genetics; Genome-Wide Association Study; Glucosylceramidase - genetics; GWAS; HLA-DQ beta-Chains - genetics; Homozygote; Humans; Internal Medicine; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics; Male; Middle Aged; Neurology; Parkinson Disease - epidemiology; Parkinson Disease - genetics; Parkinson's disease; Risk; Southern Spain; Spain - epidemiology; Synaptotagmins - genetics; Ubiquitin-Protein Ligases - genetics; Genetics; Southern Spain; GWAS; Parkinson’s disease; Parkinson's disease
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2016.06.001

Abstract Here, we set out to study the genetic architecture of Parkinson’s disease (PD) through a Genome-Wide Association Study (GWAS) in a Southern Spanish population. 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 (GRS). 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 GRS quintile showed significantly increased risk of PD versus the lowest quintile (OR=3.6, p-value < 4e-7 ), but no significant difference in AAO. We found evidence of runs of homozygosity in two PD-associated regions: one intersecting the HLA-DQB1 gene in six patients and one control; and another intersecting the GBA-SYT11 gene in one 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 one 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.