Evidence map›Paper›PMID 40123161›Full record

ArticleBrain and behavior2025

Mendelian Randomization Analysis of the Possible Causal Relationships Between Neurodevelopment-Related Proteins and Bipolar Disorder.

Yanyan Li, Qianqian Gui, Shurong Ren, Zhifen Liu, Aixia Zhang, Penghong Liu, Xueping Zhou, Ning Sun, Chunxia Yang

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Article in Brain and behavior, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Yanyan LiShanxi Medical University, Taiyuan, China.
Qianqian GuiShanxi Medical University, Taiyuan, China.
Shurong RenShanxi Medical University, Taiyuan, China.
Zhifen LiuDepartment of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
Aixia ZhangDepartment of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
Penghong LiuDepartment of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
Xueping ZhouDepartment of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
Ning SunDepartment of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
Chunxia YangDepartment of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.ORCID https://orcid.org/0000-0002-5566-3990

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBipolar disorder (BD) is a complex mental condition of which the mechanism of onset remains unclear. Mendelian randomization (MR) allows evaluation of the causal effects of biomarkers by minimizing the risks of reverse causation and confounding factors. In this study, MR was used to assess the causal relationships between neurodevelopment-related proteins and BD, thereby providing potential evidence for the neurodevelopmental hypothesis of this mental disorder.

methodsLeveraging data from large-scale genome-wide association studies (GWASs), the associations between six neurodevelopment-related proteins and BD were analyzed using five MR approaches; namely, inverse-variance weighted, weighted median, MR-Egger, simple mode, and weighted mode methods. The neurodevelopment-related proteins were selected in the study with 5368 European descents. GWAS of BD come from the Psychiatric Genomics Consortium (N

resultsThe analyses identified robust causal relationships between BD and the proteins inter-alpha-trypsin inhibitor heavy chain (ITIH)5 (OR = 1.08, 95% CI = 1.00-1.17, p = 0.04) and neurofascin (NFASC) (OR = 0.96, 95% CI = 0.92-1.00, p = 0.042). Initial findings for ITIH1 and ITIH3 were deemed unreliable due to pleiotropy (ITIH1: MR-Egger intercept p = 0.025) or heterogeneity (ITIH3: Cochran's Q p = 0.001). Furthermore, the MR analyses failed to yield evidence supporting a causal effect of liability to BD on neurodevelopment-related proteins.

conclusionThe MR analysis indicated potential causal relationships between two neurodevelopment-related proteins (NFASC and ITIH5) and BD. Further studies are required to validate these results and elucidate the specific functions of these proteins in the development of this mental disorder.

Indexed as

Bipolar DisorderMendelian Randomization AnalysisAlpha-GlobulinsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideAlpha-Globulinsinter-alpha-inhibitorbipolar disorderITIH5Mendelian randomizationneurodevelopmentNFASC

Identifiers

PMID40123161
PMCPMC11930852

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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.