Evidence map›Paper›PMID 41855073›Full record

ArticleClinical neuropharmacology

PCSK9 Inhibitors and Bipolar Disorder: A Drug Target Mendelian Randomization Study.

Jin Li, Pei-Sen Yao

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Article in Clinical neuropharmacology. 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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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Jin LiDepartment of Cardiovascular Medicine, Fujian Provincial Geriatric Hospital, Fujian Medical University Teaching Hospital.
Pei-Sen YaoDepartment of Neurosurgery, Neurosurgical Research Institute, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveBipolar disorder (BD) patients remain symptomatic. As lipid-lowering drug targets have been linked to BD risk, we used Mendelian randomization (MR) to assess their therapeutic potential.

methodsWe conducted MR analyses utilizing genetic variants associated with lipid traits and variants in genes encoding the protein targets of various classes of lipid-lowering drugs. The specific drug classes investigated included 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and Niemann-Pick C1-Like 1 (NPC1L1). To determine the effects on BD risk, we meta-analyzed MR estimates for regional variants using data from 2 large sample sets. The genetic variants were weighted based on their associations with low-density LDL-c. For lipid-modifying drug targets that exhibited suggestive significance, we further used eQTL data. In addition, we performed colocalization analysis to assess genetic confounding.

resultsGenetically proxied inhibition of PCSK9 was strongly associated with a lower risk of developing BD (IVW MR OR=0.82, 95% CI=0.74-0.91, P =2.12e-04, SD reduction in LDL-c) in PGC data set, and in UK Biobank data set ( P =0.03). Sensitivity analyses yielded no statistically significant evidence of bias arising from pleiotropy or genetic confounding. The posterior probability for a common causal variant between PCSK9 inhibition and BD risk was 80.8%.

conclusionsIt was observed that PCSK9 showed significant associations with BD risk. These findings indicate that PCSK9 inhibitors have the potential to serve for the treatment of BD.

Indexed as

Bipolar DisorderMendelian Randomization AnalysisPCSK9 InhibitorsProprotein Convertase 9Cholesterol, LDLHumansMembrane Transport ProteinsPolymorphism, Single NucleotideCholesterol, LDLMembrane Transport ProteinsNPC1L1 protein, humanPCSK9 InhibitorsPCSK9 protein, humanProprotein Convertase 9bipolar disorderdrugs targetLDLMendelian randomization

Identifiers

PMID41855073
PMCPMC13166066

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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 OpenQuestion graph.