Evidence map›Paper›PMID 42696136›Full record

ArticleEuropean archives of psychiatry and clinical neuroscience2026

Genetic interconnections between personality-related phenotypes and psychiatric disorders.

Dandan Weng, Ruiqing Fan

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Article in European archives of psychiatry and clinical neuroscience, 2026. 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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2 authors.

Dandan WengDepartment of Infectious Diseases, Yangming Hospital Affiliated to Ningbo University, Ningbo, China.
Ruiqing FanDepartment of Psychiatry, Yangming Hospital Affiliated to Ningbo University, No. 800 Chengdong Road, Yuyao City, Ningbo, 315400, Zhejiang Province, China. durenlynnvan@163.com.

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6 · The paper itself

Abstract

backgroundPersonality-related phenotypes are genetically correlated with psychiatric disorders, but whether these relationships reflect shared genetic loci and differ across individual phenotypes remains unclear. We investigated their shared genetic architecture at the level of specific phenotype-disorder pairs.

methodsWe analyzed genome-wide association study summary statistics for 13 personality-related phenotypes and eight psychiatric disorders in populations of European ancestry. Genetic correlations were evaluated separately for 104 phenotype-disorder pairs using linkage disequilibrium score regression and high-definition likelihood. For pairs supported by both methods, MTAG and CPASSOC were applied separately to identify pleiotropic signals, followed by linkage disequilibrium clumping, Bayesian colocalization, gene prioritization, functional enrichment and bidirectional two-sample Mendelian randomization analyses. No composite personality or psychiatric-disorder phenotype was constructed.

resultsAmong the 104 evaluated pairs, 77 showed significant positive genetic correlations in both analyses. Joint screening of MTAG and CPASSOC results identified pleiotropic signals in 61 pairs, comprising 1088 independent lead SNV-pair associations and 776 unique SNVs. Bayesian colocalization supported 351 signals across 42 pairs and 284 unique lead SNVs. MAGMA identified 1293 unique genes, of which 379 were prioritized by PoPS and 151 were further supported by SMR. These genes were enriched in brain tissues and biological processes involving nervous system development, synaptic organization and intercellular connectivity. Inverse-variance weighted Mendelian randomization identified 41 forward and 32 reverse associations after false-discovery-rate correction, including 21 pairs with bidirectional evidence.

conclusionThese item-resolved analyses identify widespread but heterogeneous genetic sharing between personality-related phenotypes and psychiatric disorders. The findings provide a pair-specific map of shared loci and prioritized genes, while the Mendelian randomization results should be interpreted cautiously because of residual heterogeneity and potential horizontal pleiotropy. Further validation in diverse populations and functional studies is required.

Indexed as

ColocalizationCross-trait analysisGenetic correlationGenome-wide association studyMendelian randomizationNeuroticism questionnaire itemsPleiotropyPsychiatric disorders

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