Minor Allele Frequencies and Molecular Pathways Differences for SNPs Associated with Amyotrophic Lateral Sclerosis in Subjects Participating in the UKBB and 1000 Genomes Project
Abstract
:1. Introduction
2. Materials and Methods
2.1. Workflow
2.2. Step 1: SNP Selection from UKBB
2.3. Step 2: Clump Analysis
2.4. Step 3: Minor Allele Frequency (MAF) Analysis
2.5. Step 4: SNP Enrichment Analysis
2.6. Step 5: Minor Allele Frequency Analysis of SNPs Enriched
2.7. Step 6.a and 6.b: Mapping to Gene Symbol and Altered Transcription Factor Binding
2.8. Step 7: Molecular Pathways
3. Results
3.1. 84. SNPs Differ between United Kingdom Biobank (UKBB) and the European 1000 Genome Project (1KG)
3.2. Altered Transcription Factor Binding
3.3. Molecular Pathways
4. Discussion
4.1. 46 Genes Associated with 84 SNPs That Differ between UKBB and 1KG
4.1.1. KCNMB2 and Molecular Pathways
4.1.2. SLC15A2 and Molecular Pathway
4.1.3. DUSP10 and Molecular Pathway
4.2. Pathways Enriched by Genes Whose Motives of Binding Sites Were Altered by 70 of 84 SNPs
4.2.1. Regulation of Beta-Cell Development
4.2.2. Transcriptional Regulation by RUNX3
4.2.3. Transcriptional Regulation of Pluripotent Stem Cells
4.2.4. FOXO-Mediated Transcription of Cell Death Genes
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Single Nucleotide Polymorphism | Gene Related |
---|---|
rs34567530 | SLC15A2 |
rs113741508 | LOC107985998 |
rs6666764 | - |
rs2365172 | - |
rs12749251 | HECTD3 |
Single Nucleotide Polymorphisms | Minor Allele Frequency | Gene Related |
---|---|---|
rs11546322 | 0.352,024 | RASGEF1C |
rs4575343 | 0.30,842 | MGAT4C |
Single Nucleotide Polymorphisms | Minor Allele Frequency | Gene Related |
---|---|---|
rs34567530 | 0.3882 | SLC5A2 |
rs76402 | 0.3626 | ICA |
Pathway Name | p-Value | Submitted Entities Found |
---|---|---|
Ca2+ activated K+ channels | 6.923 × 10−4 | KCNMB2 |
cGMP effects | 2.147 × 10−3 | KCNMB2 |
Nitric oxide stimulates guanylate cyclase | 4.354 × 10−3 | KCNMB2 |
Proton/oligopeptide cotransporters | 1.677 × 10−2 | SLC15A2 |
Signaling by MAPK mutants | 2.917 × 10−2 | DUSP10 |
Pathway Name | p-Value | Submitted Entities Found |
---|---|---|
Regulation of beta-celldevelopment | 6.661 × 10−16 | NR5A2, HNF4A, HNF6, HES1, HNF1B, STF1, HNF1A, FOXA3, FOXO1, FOXA2 |
Generic Transcription Pathway | 9.880 × 10−15 | SPI1, RORA, NR2E3, BACH1, GLI2, MECP2, RORG, HNF4A, SOX9, TEAD1, TEAD3, TEAD4, MSX2, PAX5, ERR1, P73, RUNX3, FOXP3, RUNX2, FOXP2, RUNX1, ELF1, NR5A2, TAL1, DDIT3, PPARG, PPARD, NR1I3, TCF7, LEF1, FOXO4, FOXO3, NR2C2, FOXO1, RXRA, HES1, RXRG, E2F6, SMAD2, NFE2, SMAD1, SMAD4, ZFHX3, SMAD3, NFYA, NFYB, VDR, NFYC, NR1H2, NR1H4, NR0B1, NR1D1, TBX5, NR2F6, NR4A3, SP1 |
Transcriptional regulation by RUNX3 | 7.648 × 10−10 | SPI1, RORA, NR2E3, BACH1, GLI2, MECP2, RORG, HNF4A, SOX9, TEAD1, TEAD3, TEAD4, MSX2, PAX5, ERR1, P73, RUNX3, FOXP3, RUNX2, FOXP2, RUNX1, ELF1, NR5A2, TAL1, DDIT3, PPARG, PPARD, NR1I3, TCF7, LEF1, FOXO4, FOXO3, NR2C2, FOXO1, RXRA, HES1, RXRG, E2F6, SMAD2, NFE2, SMAD1, SMAD4, ZFHX3, SMAD3, NFYA, NFYB, VDR, NFYC, NR1H2, NR1H4, NR0B1, NR1D1, TBX5, NR2F6, NR4A3, SP1 |
Transcriptional regulation of pluripotent stem cells | 5.635 × 10−7 | SMAD2, FOXD3, SMAD4, EPAS1, STAT3, PBX1 |
FOXO-mediated transcription of cell death genes | 6.742 × 10−7 | NFYA, NFYB, DDIT3, NFYC, FOXO4, FOXO3, FOXO1 |
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D’Antona, S.; Bertoli, G.; Castiglioni, I.; Cava, C. Minor Allele Frequencies and Molecular Pathways Differences for SNPs Associated with Amyotrophic Lateral Sclerosis in Subjects Participating in the UKBB and 1000 Genomes Project. J. Clin. Med. 2021, 10, 3394. https://doi.org/10.3390/jcm10153394
D’Antona S, Bertoli G, Castiglioni I, Cava C. Minor Allele Frequencies and Molecular Pathways Differences for SNPs Associated with Amyotrophic Lateral Sclerosis in Subjects Participating in the UKBB and 1000 Genomes Project. Journal of Clinical Medicine. 2021; 10(15):3394. https://doi.org/10.3390/jcm10153394
Chicago/Turabian StyleD’Antona, Salvatore, Gloria Bertoli, Isabella Castiglioni, and Claudia Cava. 2021. "Minor Allele Frequencies and Molecular Pathways Differences for SNPs Associated with Amyotrophic Lateral Sclerosis in Subjects Participating in the UKBB and 1000 Genomes Project" Journal of Clinical Medicine 10, no. 15: 3394. https://doi.org/10.3390/jcm10153394