Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders
Fanelli G, Franke B, De Witte W, Ruisch IH, Haavik J, van Gils V, Jansen WJ, Vos SJB et al.. Translational psychiatry, 2022-02-14
Topic: Brain proteins, microglia and lab models
The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer's disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie this observed multimorbidity. We investigated the genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise global genetic correlations using the summary statistics of the largest available genome-wide association studies for these phenotypes. Having tested these hypotheses, other potential brain "insulinopathies" were also explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Stratified covariance analyses were then performed to investigate the contribution of insulin-related gene sets. Significant negative genetic correlations were found between OCD and MetS (r g = -0.315, p = 3.9 × 10 -8 ), OCD and obesity (r g = -0.379, p = 3.4 × 10 -5 ), and OCD and T2DM (r g = -0.172, p = 3 × 10 -4 ). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p < 6.17 × 10 -4 ). Stratified analyses showed negative genetic covariances between AD, ASD, OCD, ADHD, AN, bipolar disorder, schizophrenia and somatic insulinopathies through gene sets related to insulin signalling and insulin receptor recycling, and positive genetic covariances between AN and T2DM, as well as ADHD and MetS through gene sets related to insulin processing/secretion (p < 2.06 × 10 -4 ). Overall, our findings suggest the existence of two clusters of neuropsychiatric disorders, in which the genetics of insulin-related diseases/traits may exert divergent pleiotropic effects. These results represent a starting point for a new research line on "insulinopathies" of the brain.
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APA 7th
Fanelli, G., Franke, B., De Witte, W., Ruisch, I. H., Haavik, J., van Gils, V., et al. (2022). Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders. Translational psychiatry. https://doi.org/10.1038/s41398-022-01817-0
Vancouver
Fanelli G, Franke B, De Witte W, Ruisch IH, Haavik J, van Gils V, et al. Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders. Translational psychiatry. 2022. doi:10.1038/s41398-022-01817-0. PMID: 35165256.
BibTeX
@article{fanelli2022-35165256,
author = {Fanelli, G. and Franke, B. and De Witte, W. and Ruisch, I. H. and Haavik, J. and van Gils, V. and Jansen, W. J. and Vos, S. J. B. and others},
title = {{Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders}},
journal = {Translational psychiatry},
year = {2022},
doi = {10.1038/s41398-022-01817-0},
pmid = {35165256},
url = {https://doi.org/10.1038/s41398-022-01817-0}
}
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Key findings
- Significant negative genetic correlations were found between OCD and MetS (r g = -0.315, p = 3.9 × 10 -8 ), OCD and obesity (r g = -0.379, p = 3.4 × 10 -5 ), and OCD and T2DM (r g = -0.172, p = 3 × 10 -4 ).
- Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p < 6.17 × 10 -4 ).
- Overall, our findings suggest the existence of two clusters of neuropsychiatric disorders, in which the genetics of insulin-related diseases/traits may exert divergent pleiotropic effects.
- These results represent a starting point for a new research line on "insulinopathies" of the brain.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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 multicenter collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Translational psychiatry) |
| 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 | 3 / 5 | 2022 — within 6 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35165256) |
| Free to read | 2 / 2 | Free to read |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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