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

Abstract

Gene SLC41A1 (A1) is localized within Parkinson’s disease-(PD)-susceptibility locus PARK16 and encodes for the Na+/Mg2+-exchanger. The association of several A1 SNPs with PD has been studied. Two, rs11240569 and rs823156, have been associated with reduced PD-susceptibility primarily in Asian populations. Here, we examined the association of rs11240569, rs708727, and rs823156 with PD in the Slovak population and their power to discriminate between PD patients and healthy controls. The study included 150 PD patients and 120 controls. Genotyping was performed with the TaqMan® approach. Data were analyzed by conventional statistics and Random Forest machine-learning (ML) algorithm. Individually, none of the three SNPs is associated with an altered risk for PD-onset in Slovaks. However, a combination of genotypes of SNP-triplet GG(rs11240569)/AG(rs708727)/AA(rs823156) is significantly (p < 0.05) more frequent in the PD (13.3%) than in the control (5%) cohort. ML identified the power of the tested SNPs in isolation or of their singlets (joined), duplets and triplets to discriminate between PD-patients and healthy controls as zero. Our data further substantiate differences between diverse populations regarding the association of A1 polymorphisms with PD-susceptibility. Lack of power of the tested SNPs to discriminate between PD and healthy cases render their clinical/diagnostic relevance in the Slovak population negligible.

Alzheimer’s Disease-Associated SNP rs708727 in SLC41A1 May Increase Risk for Parkinson’s Disease: Report from Enlarged Slovak Study

“…The genetic analyses were performed on A1 SNPs rs11240569, rs708727, and rs823156 in the cohort of 508 PD patients (vs. 150 patients in the pilot study) and the cohort of 472 controls (vs. 120 controls in the pilot study) [37]. Thus, the numbers of the PD patients and of the control probands were increased in this study by 3.4-fold and 3.9-fold, respectively, in comparison with the pilot study.…”

“…In 2019, we published a study showing that the three aforementioned A1 SNPs are not associated with any susceptibility toward PD in the Slovak population, as demonstrated by the means of frequentist statistics and by machine learning [37]. A major limitation of that study might have been the relatively low number of participants in both the PD (150) and the control (120) cohorts.…”

Machine Learning for the Diagnosis of Parkinson's Disease: A Review of Literature

“…Ten studies (4.8%) used data that do not belong to any categories mentioned above, such as single nucleotide polymorphisms (Cibulka et al, 2019 ) (SNPs), electromyography (EMG) (Kugler et al, 2013 ), OCT (Nunes et al, 2019 ), cardiac scintigraphy (Nuvoli et al, 2019 ), Patient Questionnaire of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (Prashanth and Dutta Roy, 2018 ), whole-blood gene expression profiles (Shamir et al, 2017 ), transcranial sonography (Shi et al, 2018 ) (TCS), eye movements (Tseng et al, 2013 ), electroencephalography (EEG) (Vanegas et al, 2018 ), and serum samples (Váradi et al, 2019 ).…”

Dietary Mg2+ Intake and the Na+/Mg2+ Exchanger SLC41A1 Influence Components of Mitochondrial Energetics in Murine Cardiomyocytes

“…In order to analyze the activities of ACON, ICDH, KGDH, CI, CII, CIII, CIV, and CV/F 1 F o -ATPase as potential predictors/discriminators between the types of Mg diet fed to MK-1 mice (LMgD vs. NMgD) and between the Slc41a1 genotypes of the animals (Slc41a1 −/− vs. Slc41a1 +/+ ), we trained the RFM-L algorithm using our data. The algorithm evaluated the discriminative importance of individual activities of the tested Krebs cycle enzymes and ETC complexes by a technical construct known as graph depth [45]. The predictive ability of these enzymes/enzyme complexes was visualized by ROC curves and quantified by AUC.…”

“…The predictive ability of these enzymes/enzyme complexes was visualized by ROC curves and quantified by AUC. A perfect discriminative ability of predictors is associated with 100% AUC; 50% AUC (or less) corresponds to no discriminative ability [45]. The best discriminative ability between mitochondria isolated from the hearts of animals fed with LMgD and mitochondria isolated from the hearts of animals fed with NMgD (irrespective of their Slc41a1 genotype) were computed for the activity of ICDH followed by the activities of CIV > CV > CI ( Figure 9A).…”