Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features
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 iden...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Hindawi Limited
2023-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2023/2893662 |
| _version_ | 1797731217642094592 |
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| author | Arash Yaghoobi Homa Seyedmirzaei Moein Ala |
| author_facet | Arash Yaghoobi Homa Seyedmirzaei Moein Ala |
| author_sort | Arash Yaghoobi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T11:55:36Z |
| format | Article |
| id | doaj.art-4ba0c7c7574b47eba4a41c816b479a71 |
| institution | Directory Open Access Journal |
| issn | 2042-0080 |
| language | English |
| last_indexed | 2024-03-12T11:55:36Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj.art-4ba0c7c7574b47eba4a41c816b479a712023-08-31T00:00:01ZengHindawi LimitedParkinson's Disease2042-00802023-01-01202310.1155/2023/2893662Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging FeaturesArash Yaghoobi0Homa Seyedmirzaei1Moein Ala2Institute for Research in Fundamental Sciences (IPM)Interdisciplinary Neuroscience Research Program (INRP)Experimental Research CenterIntroduction. 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.http://dx.doi.org/10.1155/2023/2893662 |
| spellingShingle | Arash Yaghoobi Homa Seyedmirzaei Moein Ala Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features Parkinson's Disease |
| title | Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features |
| title_full | Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features |
| title_fullStr | Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features |
| title_full_unstemmed | Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features |
| title_short | Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features |
| title_sort | genome and exome wide association studies revealed candidate genes associated with datscan imaging features |
| url | http://dx.doi.org/10.1155/2023/2893662 |
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