Multigene overlap analysis of bipolar disorder subtypes and educational attainment

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-04-02 DOI:10.1016/j.pnpbp.2025.111358

Jianfei Zhang , Wanqi Wang , Yanmin Peng

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引用次数: 0

Abstract

Objective

Bipolar disorder subtypes (BIP-I and BIP-II) differ in clinical presentation and genetic basis, yet their patterns of genetic association with educational attainment (EA) remain poorly understood. This study investigated the genetic overlap between BIP subtypes and EA, along with their underlying molecular mechanisms.

Methods

Using genome-wide association study (GWAS) data for BIP-I (n = 25,060), BIP-II (n = 6781), and EA (n = 765,283), we estimated genetic overlap using bivariate causal mixed models (MiXeR) and identified shared gene loci through the joint false discovery rate (conjFDR) method.

Results

MiXeR analysis revealed approximately 7.4 K single nucleotide polymorphisms (SNPs) shared between BIP-I and EA, accounting for 97.4 % of SNPs influencing BIP-I and 56.5 % of those affecting EA. ConjFDR identified 264 loci commonly associated with BIP-I and EA, including 168 novel loci for both traits. Among the 312 lead SNPs at these loci, 219 exhibited consistent effects, while 93 demonstrated opposing effects. In contrast, only two loci were co-associated between BIP-II and EA. Functional annotation and enrichment analyses showed that most loci shared by BIP-I and EA were located in intronic and intergenic regions, with associated genes enriched in processes such as protein binding and nervous system development.

Conclusions

This study highlights the distinct degrees and patterns of genetic association between BIP subtypes and EA, offering insights into the heterogeneity of BIP and a potential genetic basis for clinical subtyping and personalized treatment strategies.

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双相情感障碍亚型与受教育程度的多基因重叠分析

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来源期刊

Progress in Neuro-Psychopharmacology & Biological Psychiatry 医学-精神病学

CiteScore

12.00

自引率

1.80%

发文量

153

审稿时长

56 days

期刊介绍： Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.