Topic: Genetics and APOE
PURPOSE OF REVIEW: Neurodegenerative diseases, neuropsychiatric disorders, and related traits have highly complex etiologies but are also highly heritable and identifying the causal genes and biological pathways underlying these traits may advance the development of treatments and preventive strategies. While many genome-wide association studies (GWAS) have successfully identified variants contributing to polygenic neurodegenerative and neuropsychiatric phenotypes including Alzheimer's disease (AD), schizophrenia (SCZ), and bipolar disorder (BPD) amongst others, interpreting the biological roles of significantly-associated variants in the genetic architecture of these traits remains a significant challenge. Here we review several 'omics' approaches which attempt to bridge the gap from associated genetic variants to phenotype by helping define the functional roles of GWAS loci in the development of neuropsychiatric disorders and traits. RECENT FINDINGS: Several common 'omics' approaches have been applied to examine neuropsychiatric traits, such as nearest-gene mapping, trans-ethnic fine mapping, annotation enrichment analysis, transcriptomic analysis, and pathway analysis, and each of these approaches has strengths and limitations in providing insight into biological mechanisms. One popular emerging method is the examination of tissue-specific genetically-regulated gene expression (GReX), which aggregates the genetic variants' effects at the gene-level. Furthermore, proteomic, metabolomic, and microbiomic studies and phenome-wide association studies will further enhance our understanding of neuropsychiatric traits. SUMMARY: GWAS has been applied to neuropsychiatric traits for a decade, but our understanding about the biological function of identified variants remains limited. Today, technological advancements have created analytical approaches for integrating transcriptomics, metabolomics, proteomics, pharmacology and toxicology as tools for understanding the functional roles of genetics variants. These data, as well as the broader clinical information provided by electronic health records, can provide additional insight and complement genomic analyses.
Key findings
- While many genome-wide association studies (GWAS) have successfully identified variants contributing to polygenic neurodegenerative and neuropsychiatric phenotypes including Alzheimer's disease (AD), schizophrenia (SCZ), and bipolar disorder (BPD) amongst others, interpreting the biological roles of significantly-associated variants in the genetic architecture of these traits remains a significant challenge.
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Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 22 of the 56 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Current genetic medicine reports) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33312764) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 22 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 22 of the 56 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | — |
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APA 7th
Chen, H.-H., Petty, L. E., Bush, W., Naj, A. C., & Below, J. E. (2019). GWAS and Beyond: Using Omics Approaches to Interpret SNP Associations. Current genetic medicine reports. https://doi.org/10.1007/s40142-019-0159-z
Vancouver
Chen H.-H, Petty LE, Bush W, Naj AC, Below JE. GWAS and Beyond: Using Omics Approaches to Interpret SNP Associations. Current genetic medicine reports. 2019. doi:10.1007/s40142-019-0159-z. PMID: 33312764.
BibTeX
@article{chen2019-33312764,
author = {Chen, Hung-Hsin and Petty, Lauren E and Bush, William and Naj, Adam C and Below, Jennifer E},
title = {{GWAS and Beyond: Using Omics Approaches to Interpret SNP Associations}},
journal = {Current genetic medicine reports},
year = {2019},
doi = {10.1007/s40142-019-0159-z},
pmid = {33312764},
url = {https://doi.org/10.1007/s40142-019-0159-z}
}