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.
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.
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.
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).
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).