PARK16 is associated with PD in the Malaysian population

Abstract

PARK16 was identified as a risk factor for Parkinson's disease in a Japanese cohort; however, subsequent studies in the other populations including the Chinese, European, Caucasian, and Chilean have shown a protective role instead. To investigate this locus in our Malaysian cohort, 1,144 individuals were screened for five SNPs in the PARK16 locus and logistic regression analysis showed that the A allele of the rs947211 SNP reduced the risk of developing PD via a recessive model (Odds ratio 0.57, P-value 0.0003). Pooled analysis with other Asian studies showed that A allele of the rs947211 SNP decreased the risk of developing PD via a recessive model (Odds ratio 0.71, P-value 0.0001). In addition, when meta-analysis was performed with other Asian population, three SNPs (rs823128, rs823156, and rs11240572) reduced risk of developing PD via a dominant model. © 2016 Wiley Periodicals, Inc.

SNPs rs11240569, rs708727, and rs823156 in SLC41A1 Do Not Discriminate Between Slovak Patients with Idiopathic Parkinson’s Disease and Healthy Controls: Statistics and Machine-Learning Evidence

“…However, in our case, the minor allele at rs823156 seems interestingly to be more frequent in the PD cohort than in the control cohort, whereas in other previously reported studies, this was vice versa. Similar to two other tested SNPs, rs823156 in our study has not been established as being associated with PD, hence indicating a similar outcome as in the eastern Chinese, Malaysian, and Spanish studies [29,32,33].…”

“…In all instances, the machine-learning approach leads to essentially a zero result, indicating no diagnostic relevance (in terms of PD diagnostics and prediction) of SNPs rs11240569, rs708727, and rs823156 in the Slovak population. From the larger perspective, our data further substantiate the proposed ethnic and interracial differences between diverse populations with regard to the statistical association of the studied A1 SNPs with the idiopathic form of PD [29,32,33,49]. Furthermore, the broader utilization of machine-learning in the assessment of the clinical relevance of various SNPs should be encouraged because, despite the statistical significance of the association of any SNP with a disease condition, which is entirely dependent on the sample size, its diagnostic power (to discriminate ill from healthy individual) might still be negligible.…”

“…The minor allele G at A1 SNP rs823156 has been associated with a reduced risk of PD onset in mainland Chinese (minor allele population frequency range (MAPFR) up to 16.1% in idiopathic PD and 20.6% in control cohorts), Japanese (MAPFR up to 14% in PD and 19% in control cohorts), and Korean (MAPFR up to 18% in PD and 21% in control cohorts) populations [28,30,31]. On the contrary, it is not associated with an altered risk for developing PD in eastern Chinese (MAPFR up to 18.58% in PD and 22.39% in control cohorts), Malaysian (MAPFR up to 19.31% in PD and 21.19% in control cohorts) and Spanish (MAPFR up to 16% in PD and 17% in control cohorts) populations [29,32,33]. The MAPFR for allele G at rs823156 in our PD (19%) and control (15%) cohorts clearly falls within the MAPFR range set for allele G in other studies.…”

“…In a study conducted with north Spanish cohorts of PD patients and controls, Mata and colleagues have not confirmed the association between SNP rs823156 and susceptibility to PD seen prevalently in Asian populations [32]. The same is the case for the recent study of Gopalai and colleagues in the Malaysian population [33].…”

The effect of the PARK16 rs11240572 variant on brain structure in Parkinson's disease

“…The PARK16 locus, which is strongly associated with PD, was rst identi ed by a genome-wide association study in a Japanese population (Satake et al, 2009). Subsequently, its role was con rmed in various regions, including Europe, China, Singapore, Chile and Malaysia, and also in the Jewish population (Simón-Sánchez et al, 2009; Tan et al, 2010; Liu et al, 2011;Mata et al, 2011;Ramirez et al, 2011;Gopalai et al, 2016). Within PARK16, rs11240572 is the variant most robustly associated with risk modulation of PD in a Chinese population (Tan et al, 2010).…”