Genetic Analysis of Six Transmembrane Protein Family Genes in Parkinson’s Disease in a Large Chinese Cohort

Zhao, Yuwen; Zhang, Kailin; Pan, Hongxu; Wang, Yige; Zhou, Xiaoxia; Xiang, Yaqin; Xu, Qian; Sun, Qiying; Tan, Jieqiong; Yan, Xinxiang; Li, Jinchen; Guo, Jifeng; Tang, Beisha; Liu, Zhenhua

doi:10.3389/fnagi.2022.889057

Cited by 13 publications

(6 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transmembrane Protein ( TMEM ) family members, TMEM132D and TMEM196 were also found among the stringent downregulated transcripts, and TMEM132D was also found to be important among the different prediction models. Polymorphisms of the TMEM family of genes have been shown to be associated with Parkinson’s disease [ 52 , 53 ]. KBTBD11 polymorphism was also found to be associated with cognitive decline [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide transcriptome profiling and development of age prediction models in the human brain

Zarrella,

Tsurumi

2024

Aging

View full text Add to dashboard Cite

Aging-related transcriptome changes in various regions of the healthy human brain have been explored in previous works, however, a study to develop prediction models for age based on the expression levels of specific panels of transcripts is lacking. Moreover, studies that have assessed sexually dimorphic gene activities in the aging brain have reported discrepant results, suggesting that additional studies would be advantageous. The prefrontal cortex (PFC) region was previously shown to have a particularly large number of significant transcriptome alterations during healthy aging in a study that compared different regions in the human brain. We harmonized neuropathologically normal PFC transcriptome datasets obtained from the Gene Expression Omnibus (GEO) repository, ranging in age from 21 to 105 years, and found a large number of differentially regulated transcripts in the old and elderly, compared to young samples overall, and compared female and male-specific expression alterations. We assessed the genes that were associated with age by employing ontology, pathway, and network analyses. Furthermore, we applied various established (least absolute shrinkage and selection operator (Lasso) and Elastic Net (EN)) and recent (eXtreme Gradient Boosting (XGBoost) and Light Gradient Boosting Machine (LightGBM)) machine learning algorithms to develop accurate prediction models for chronological age and validated them. Studies to further validate these models in other large populations and molecular studies to elucidate the potential mechanisms by which the transcripts identified may be related to aging phenotypes would be advantageous.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome-wide transcriptome profiling and development of age prediction models in the human brain

Zarrella,

Tsurumi

2024

Aging

View full text Add to dashboard Cite

show abstract

“…Mixed statistical models were used and corrected for the following confounding factors in genome-wide association analyses: genetic relatedness and population structure (ethnicity). The details of the GCTA software and mixed model association methods have been described elsewhere [ 22 , 23 ]. The mathematical equation of this statistical model is as follows.…”

Section: Methodsmentioning

confidence: 99%

Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features

Yaghoobi,

Seyedmirzaei,

Ala

2023

Parkinson's Disease

View full text Add to dashboard Cite

Introduction. Despite remarkable progress in identifying Parkinson’s disease (PD) genetic risk loci, the genetic basis of PD remains largely unknown. With the help of the endophenotype approach and using data from dopamine transporter single-photon emission computerized tomography (DaTscan), we identified potentially involved genes in PD. Method. We conducted an imaging genetic study by performing exome-wide association study (EWAS) and genome-wide association study (GWAS) on the specific binding ratio (SBR) of six DaTscan anatomical areas between 489 and 559 subjects of Parkinson’s progression markers initiative (PPMI) cohort and 83,623 and 36,845 single-nucleotide polymorphisms (SNPs)/insertion-deletion mutations (INDELs). We also investigated the association of cerebrospinal fluid (CSF) protein concentration of our significant genes with PD progression using PPMI CSF proteome data. Results. Among 83,623 SNPs/INDELs in EWAS, one SNP (rs201465075) on 1 q32.1 locus was significantly ( P value = 4.03 × 10−7) associated with left caudate DaTscan SBR, and 33 SNPs were suggestive. Among 36,845 SNPs in GWAS, one SNP (rs12450112) on 17 p.12 locus was significantly ( P value = 1.34 × 10−6) associated with right anterior putamen DaTscan SBR, and 39 SNPs were suggestive among which 8 SNPs were intergenic. We found that rs201465075 and rs12450112 are most likely related to IGFN1 and MAP2K4 genes. The protein level of MAP2K4 in the CSF was significantly associated with PD progression in the PPMI cohort; however, proteomic data were not available for the IGFN1 gene. Conclusion. We have shown that particular variants of IGFN1 and MAP2K4 genes may be associated with PD. Since DaTscan imaging could be positive in other Parkinsonian syndromes, caution should be taken when interpreting our results. Future experimental studies are also needed to verify these findings.

show abstract

“…Transmembrane protein 59 (TMEM59) is a membrane protein involving in many cell processes including signal transduction and cell adhesion [ 8 ]. The antitumor effects of TMEM59 have been found in glioma [ 9 ], neuroblastoma [ 10 ] and gastric cancer [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circTMEM59 inhibits progression of pancreatic ductal adenocarcinoma by targeting miR-147b/SOCS1: An in vitro study

Cao,

Hong,

et al. 2024

Heliyon

View full text Add to dashboard Cite

Genetic Analysis of Six Transmembrane Protein Family Genes in Parkinson’s Disease in a Large Chinese Cohort

Cited by 13 publications

References 43 publications

Genome-wide transcriptome profiling and development of age prediction models in the human brain

Genome-wide transcriptome profiling and development of age prediction models in the human brain

Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features

Circular RNA circTMEM59 inhibits progression of pancreatic ductal adenocarcinoma by targeting miR-147b/SOCS1: An in vitro study

Contact Info

Product

Resources

About