Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression
Kohannim O, Hibar DP, Stein JL, Jahanshad N, Hua X, Rajagopalan P, Toga AW, Jack CR et al.. Frontiers in neuroscience, 2012-08-06
Topic: Brain proteins, microglia and lab models
We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8 ± 2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.
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APA 7th
Kohannim, O., Hibar, D. P., Stein, J. L., Jahanshad, N., Hua, X., Rajagopalan, P., et al. (2012). Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression. Frontiers in neuroscience. https://doi.org/10.3389/fnins.2012.00115
Vancouver
Kohannim O, Hibar DP, Stein JL, Jahanshad N, Hua X, Rajagopalan P, et al. Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression. Frontiers in neuroscience. 2012. doi:10.3389/fnins.2012.00115. PMID: 22888310.
BibTeX
@article{kohannim2012-22888310,
author = {Kohannim, O. and Hibar, D. P. and Stein, J. L. and Jahanshad, N. and Hua, X. and Rajagopalan, P. and Toga, A. W. and Jack, C. R. and others},
title = {{Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression}},
journal = {Frontiers in neuroscience},
year = {2012},
doi = {10.3389/fnins.2012.00115},
pmid = {22888310},
url = {https://doi.org/10.3389/fnins.2012.00115}
}
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Key findings
- This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS.
- The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes.
- The most significantly associated gene was an autism susceptibility gene known as MACROD2.
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Study details
- Participants729
- Evidence strengthModerate
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported 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 and multi-centre collaboration, so those were left out: it earned 30 of the 58 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in neuroscience) |
| 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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 729 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 22888310) |
| Free to read | 2 / 2 | Free to read |
| Points | 30 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 30 of the 58 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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