Abstract
Background
Patients with sporadic Alzheimer’s do not possess an identified causative variant and hold an estimated heritability of 92–100%. Majority of disease causing, or protective mutations were uncommon in a generic group of the population, whereas dominant variants were well identified. Development of next-generation sequencing along with genome-wide association studies allowed to accurately identify the lesser-known disease-causing variants essential for the early detection of AD in sporadic patients to provide genetic counsel and prophylactic treatment.
Objective
The objective of the review is to bring the focus to the potentiality of large-scale GWAS (Genome-Wide Association Studies) analysis for the detection of novel genes for the sporadic Alzheimer’s disease.
Results
Identification of infrequently studied genes like LILRB2, LIPC, ITGAX, HLA-A, CASP8, ABCA7, ADAM10, BIN1, CD33, CLU, EPHA1, GAB2, PICALM, TREM2, SORL1, MAPT, HLA for the sporadic AD, that interact with predominant AD genes and engages in pathways mediating disease progression.
Conclusion
A multi-population large-scale un-targeted whole-genome GWAS or WES (whole exome sequencing) analysis is needed to identify several genes and variants besides the predominantly studied APOE for the sporadic case of Alzheimer’s.
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Abbreviations
- AD:
-
Allele depth
- AD:
-
Alzheimer’s disease
- ALS:
-
Amyotrophic lateral sclerosis
- ALT:
-
Alternate allele
- APOE:
-
Apolipoprotein
- APP:
-
Amyloid precursor protein
- BAM:
-
Binary alignment map
- BWA:
-
Burrows-wheeler alignment tool
- CHROM:
-
Chromosome
- Cytc:
-
Cytochrome-c
- DP:
-
Read depth
- EOAD:
-
Early onset Alzheimer’s disease
- FAD:
-
Familial Alzheimer’s disease
- fEOAD:
-
Familial early onset Alzheimer’s disease
- FTD:
-
Fronto-temporal dementia
- GATK:
-
Genome analysis toolkit
- GQ:
-
Genotype quality
- GT:
-
Genotype
- GWAS:
-
Genome-wide association studies
- InDels:
-
Insertions and deletions
- INFO:
-
Genotype information
- LDL:
-
Low-density lipoprotein
- LDLR:
-
Low-density lipoprotein receptor
- LOAD:
-
Late-onset Alzheimer’s disease
- MAF:
-
Minor allele frequency
- NGS:
-
Next generation studies
- PD:
-
Parkinson’s disease
- PirB:
-
Paired immunoglobulin-like receptor B
- POS:
-
Position
- PRS:
-
Polygenic risk score
- PSEN1:
-
Presenilin 1
- PSEN2:
-
Presenilin 2
- QC:
-
Quality control
- QUAL:
-
Quality score
- REF:
-
Reference allele
- ROS:
-
Reactive oxygen species
- SAD:
-
Sporadic Alzheimer’s disease
- SAM:
-
Sequence alignment map
- SD:
-
Standard deviation
- sEOAD:
-
Sporadic early onset Alzheimer’s disease
- SNP:
-
Single nucleotide polymorphism
- VCF:
-
Variant calling format
- WES:
-
Whole exome sequencing
- WGS:
-
Whole genome sequencing
- Wnt:
-
Wingless-related integration site
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The research was funded by the Gachon University Research Grant (2019-0357 and GCU-2019-0815).
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Jaya Bagaria declares no conflict of interest. Kwangsik Nho declares no conflict of interest. Seong Soo A. An declares no conflict of interest.
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Bagaria, J., Nho, K. & An, S.S.A. Importance of GWAS in finding un-targeted genetic association of sporadic Alzheimer’s disease. Mol. Cell. Toxicol. 17, 233–244 (2021). https://doi.org/10.1007/s13273-021-00130-z
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DOI: https://doi.org/10.1007/s13273-021-00130-z