Evidence mapPaperPMID 38293198Full record

ArticlemedRxiv : the preprint server for health sciences2024

Large-Scale Mendelian Randomization Study Reveals Circulating Blood-based Proteomic Biomarkers for Psychopathology and Cognitive Task Performance.

Upasana Bhattacharyya, Jibin John, Max Lam, Jonah Fisher, Benjamin Sun, Denis Baird, Chia-Yen Chen, Todd Lencz

Open access · greenAbstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Upasana BhattacharyyaInstitute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY.ORCID 0000-0002-9264-262X
Jibin JohnInstitute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY.
Max LamInstitute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY.ORCID 0000-0002-4256-7844
Jonah FisherBiogen Inc., Cambridge, MA.
Benjamin SunBiogen Inc., Cambridge, MA.
Denis BairdBiogen Inc., Cambridge, MA.
Chia-Yen ChenBiogen Inc., Cambridge, MA.
Todd LenczInstitute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY.ORCID 0000-0001-8586-338X
Biogen (United States) · USFeinstein Institute for Medical Research · US

Funding

Cognitive Genomics as a Window on Neurodevelopment and PsychopathologyR01MH117646 · NIMH · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI TODD LENCZ · 2018 to 2026
$4.7M
Training Program for Psychiatric Genetics in IndiaD43TW006167 · FIC · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NIMGAONKAR, VISHWAJIT LAXMIKANT · 2002 to 2006
$1.7M
Tri National Training Program in Psychiatric GeneticsD43TW008302 · FIC · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MANSOUR, HADER A., NIMGAONKAR, VISHWAJIT LAXMIKANT · 2009 to 2013
$542k
FIC NIH HHS D43 TW006167FIC NIH HHS D43 TW008302NIMH NIH HHS R01 MH117646
6 · The paper itself

Abstract

Background: Research on peripheral (e.g., blood-based) biomarkers for psychiatric illness has typically been low-throughput in terms of both the number of subjects and the range of assays performed. Moreover, traditional case-control studies examining blood-based biomarkers are subject to potential confounds of treatment and other exposures common to patients with psychiatric illnesses. Our research addresses these challenges by leveraging large-scale, high-throughput proteomics data and Mendelian Randomization (MR) to examine the causal impact of circulating proteins on psychiatric phenotypes and cognitive task performance. Methods: We utilized plasma proteomics data from the UK Biobank (3,072 proteins assayed in 34,557 European-ancestry individuals) and deCODE Genetics (4,719 proteins measured across 35,559 Icelandic individuals). Significant proteomic quantitative trait loci (both cis-pQTLs and trans-pQTLs) served as MR instruments, with the most recent GWAS for schizophrenia, bipolar disorder, major depressive disorder, and cognitive task performance (all excluding overlapping UK Biobank participants) as phenotypic outcomes. Results: MR revealed 109 Bonferroni-corrected causal associations (44 novel) involving 88 proteins across the four phenotypes. Several immune-related proteins, including interleukins and complement factors, stood out as pleiotropic across multiple outcome phenotypes. Drug target enrichment analysis identified several novel potential pharmacologic repurposing opportunities, including anti-inflammatory agents for schizophrenia and bipolar disorder and duloxetine for cognitive performance. Conclusions: Identification of causal effects for these circulating proteins suggests potential biomarkers for these conditions and offers insights for developing innovative therapeutic strategies. The findings also indicate substantial evidence for the pleiotropic effects of many proteins across different phenotypes, shedding light on the shared etiology among psychiatric conditions and cognitive ability.

Identifiers

PMID38293198
PMCPMC10827252
OpenAlexW4391050602

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.