We used 2 PD case-control data sets (Washington University and the Parkinson's Progression Markers Initiative) to determine whether polymorphisms located at the GWAS top hits (GBA, ACMSD/TMEM163, STK39, MCCC1/LAMP3, GAK/TMEM175, SNCA, and MAPT) show association with AAO or motor progression.
Herein, we investigated the effect of top three PD-associated genetic variants related to amino acid catabolism in Caucasians listed on the top risk loci identified by meta-analysis of genome-wide association studies in PDGene database, including aminocarboxymuconate-semialdehyde decarboxylase- (<i>ACMSD-</i>) transmembrane protein 163 (<i>TMEM163</i>) rs6430538, methylcrotonyl-CoA carboxylase 1 (<i>MCCC1</i>) rs12637471, and branched-chain ketoacid dehydrogenase kinase- (<i>BCKDK-</i>) syntaxin 1B (<i>STX1B</i>) rs14235, by genotyping 599 Taiwanese patients with PD and 598 age-matched control subjects.
In the meta-analysis study no loci reached a genome-wide significance level (P<5xE-8), but a suggestive association (P-value = 1.04E-6) between rs6430538 (ACMSD/TMEM163) and an increased risk of PD was found.
The first large-scale meta-analysis of published genome-wide association studies (GWAS) in Parkinson's disease (PD) identified 5 new genetic loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R).
Our data suggest that not only common genetic variability but also rare variants in ACMSD alone or in combination with other risk factors might increase the risk of PD.
A meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe found 11 loci that surpassed the threshold for genome-wide significance (p<5×10(-8)), and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11 and CCDC62/HIP1R).