Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Set
2.2. Genetic Model
2.3. LASSO
2.4. Group LASSO
2.5. Pairwise Interaction Model
2.6. Hierarchical Group LASSO Regularization
2.7. Implementation
2.8. Descriptive and Analytical Statistics
2.9. In Silico Analysis
3. Results and Discussion
3.1. Variable Selection
3.2. Pairwise Interaction Selection
3.3. LASSO and Related Approaches in Variable Selection
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ALS | Amyotrophic Lateral Sclerosis |
GWAS | Genome-Wide Association Studies |
SNP | Single-Nucleotide Polymorphism |
LASSO | Least Absolute Shrinkage and Selection Operator |
eQTL | Expression Quantitative Trait Loci |
QC | Quality Control |
OR | Odds Ratio |
CI | Confidence Interval |
LRT | Likelihood Ratio Test |
KCNS3 | Potassium Voltage-Gated Channel Subfamily S member 3 |
FMN2 | Formine-2 |
RGM | Repulsive Guidance Molecules |
RGMA | Repulsive Guidance Molecule Co-Receptor A |
BMP | Bone Morphogenetic Protein |
LINC02055 | Long Intergenic Non-Protein Coding RNA 2055 |
RPS6 | Ribosomal Protein S6 |
TMEM132C | Transmembrane Protein 132C |
GOLGA8B | Golgin A8 Family Member B |
TRP | Transient Receptor Potential |
TRPM | Melastatin Transient Receptor Potential |
ncRNA | Non-Coding RNA |
BCHE | Butyrylcholinesterase |
ACHE | Acetylcholinesterase |
BCL6 | B-Cell Lymphoma 6 |
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Variant (Minor Allele) | Total n | ALS n (%) | OR | 95%CI | p-Value |
---|---|---|---|---|---|
rs16984239 (A) | |||||
0 | 378 | 165 (0.44) | reference | ||
1 | 153 | 104 (0.68) | 2.74 | 1.85; 4.10 | <0.001 |
2 | 13 | 7 (0.54) | 1.51 | 0.49; 4.76 | 0.469 |
rs1037666 (C) | |||||
0 | 247 | 151 (0.61) | reference | ||
1 | 242 | 100 (0.41) | 0.45 | 0.31; 0.64 | <0.001 |
2 | 55 | 25 (0.45) | 0.53 | 0.29; 0.95 | 0.035 |
rs10459680 (T) | |||||
0 | 281 | 118 (0.42) | reference | ||
1 | 230 | 142 (0.62) | 2.23 | 1.56; 3.19 | <0.001 |
2 | 33 | 16 (0.48) | 1.30 | 0.63; 2.69 | 0.477 |
rs4552942 (C) | |||||
0 | 277 | 165 (0.60) | reference | ||
1 | 226 | 090 (0.40) | 0.45 | 0.31; 0.64 | <0.001 |
2 | 41 | 21 (0.51) | 0.71 | 0.37; 1.38 | 0.313 |
rs10773543 (G) | |||||
0 | 230 | 142 (0.62) | reference | ||
1 | 261 | 109 (0.42) | 0.44 | 0.31; 0.64 | <0.001 |
2 | 53 | 25 (0.47) | 0.55 | 0.30; 1.01 | 0.054 |
rs2241493 (C) | |||||
0 | 345 | 198 (0.57) | reference | ||
1 | 180 | 067 (0.37) | 0.44 | 0.30; 0.64 | <0.001 |
2 | 19 | 11 (0.58) | 1.02 | 0.40; 2.70 | 0.966 |
rs1436918 (A) | |||||
0 | 129 | 061 (0.47) | reference | ||
1 | 288 | 171 (0.59) | 1.63 | 1.07; 2.48 | 0.022 |
2 | 127 | 44 (0.35) | 0.59 | 0.36; 0.98 | 0.040 |
SNP | Chr:Location | Gene | Consequence | Phenotype | Citation |
---|---|---|---|---|---|
First step | |||||
rs16984239 | 2:18053180 | - | intergenic | ALS | [12,30,31,32,33] |
rs1037666 | 1:240195185 | FMN2 | intronic | ALS | [12] |
rs10459680 | 15:93138241 | LOC101927025 | intronic | ALS | [12] |
rs4552942 | 8:135862080 | LINC02055 | intronic | ALS; core binding factor acute myeloid leukemia | [12,34] |
rs10773543 | 12:128439181 | TMEM132C | intronic | ALS | [12] |
rs2241493 | 15:31070149 | TRPM1 | missense | Congenital stationary night blindness, type 1C | [35,36,37,38,39] |
rs1436918 | 15:34644720 | LOC390569 | regulatory genomic region | ALS | [12,40] |
Second step | |||||
rs2118657 | 3:165864723 | - | intergenic | - | - |
rs3172469 | 3:187741300 | BCL6 | intronic | Myeloma; non-Hodgkin lymphoma | [41,42] |
Variant (Minor Allele) | Total n | ALS n (%) | OR | 95%CI | p-Value |
---|---|---|---|---|---|
rs2118657 (T) = 0 | |||||
rs16984239 (A) = 0 | 189 | 61 (0.32) | reference | ||
rs16984239 (A) = 1 | 83 | 55 (0.66) | 4.12 | 2.38; 7.13 | <0.001 |
rs16984239 (A) = 2 | 7 | 6 (0.86) | 12.59 | 1.48; 106.89 | 0.020 |
rs2118657 (T) = 1 | |||||
rs16984239 (A) = 0 | 162 | 93 (0.57) | reference | ||
rs16984239 (A) = 1 | 64 | 46 (0.72) | 1.90 | 1.01; 3.55 | 0.046 |
rs16984239 (A) = 2 | 6 | 1 (0.17) | 0.15 | 0.02; 1.30 | 0.085 |
rs2118657 (T) = 2 | |||||
rs16984239 (A) = 0 | 27 | 11 (0.41) | reference | ||
rs16984239 (A) = 1 | 6 | 3 (0.50) | 1.45 | 0.25; 8.58 | 0.679 |
rs16984239 (A) = 2 | - | - | - | - | - |
rs3172469 (G) = 0 | |||||
rs16984239 (A) = 0 | 200 | 65 (0.33) | reference | ||
rs16984239 (A) = 1 | 83 | 55 (0.66) | 4.08 | 2.37; 7.02 | <0.001 |
rs16984239 (A) = 2 | 8 | 4 (0.50) | 2.08 | 0.50; 8.57 | 0.312 |
rs3172469 (G) = 1 | |||||
rs16984239 (A) = 0 | 150 | 84 (0.56) | reference | ||
rs16984239 (A) = 1 | 63 | 45 (0.71) | 1.96 | 1.04; 3.71 | 0.037 |
rs16984239 (A) = 2 | 5 | 3 (0.60) | 1.18 | 0.19; 7.26 | 0.859 |
rs3172469 (G) = 2 | |||||
rs16984239 (A) = 0 | 28 | 61 (0.47) | reference | ||
rs16984239 (A) = 1 | 7 | 4 (0.57) | 1.00 | 0.19; 5.33 | 0.999 |
rs16984239 (A) = 2 | - | - | - | - | - |
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Feronato, S.G.; Silva, M.L.M.; Izbicki, R.; Farias, T.D.J.; Shigunov, P.; Dallagiovanna, B.; Passetti, F.; dos Santos, H.G. Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach. J. Pers. Med. 2022, 12, 1330. https://doi.org/10.3390/jpm12081330
Feronato SG, Silva MLM, Izbicki R, Farias TDJ, Shigunov P, Dallagiovanna B, Passetti F, dos Santos HG. Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach. Journal of Personalized Medicine. 2022; 12(8):1330. https://doi.org/10.3390/jpm12081330
Chicago/Turabian StyleFeronato, Sofia Galvão, Maria Luiza Matos Silva, Rafael Izbicki, Ticiana D. J. Farias, Patrícia Shigunov, Bruno Dallagiovanna, Fabio Passetti, and Hellen Geremias dos Santos. 2022. "Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach" Journal of Personalized Medicine 12, no. 8: 1330. https://doi.org/10.3390/jpm12081330
APA StyleFeronato, S. G., Silva, M. L. M., Izbicki, R., Farias, T. D. J., Shigunov, P., Dallagiovanna, B., Passetti, F., & dos Santos, H. G. (2022). Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach. Journal of Personalized Medicine, 12(8), 1330. https://doi.org/10.3390/jpm12081330