Evidence map›Paper›PMID 39511343›Full record

ArticleNature human behaviour2025

Large-scale exome sequencing identified 18 novel genes for neuroticism in 394,005 UK-based individuals.

Xin-Rui Wu, Ze-Yu Li, Liu Yang, Ying Liu, Chen-Jie Fei, Yue-Ting Deng, Wei-Shi Liu, Bang-Sheng Wu, Qiang Dong, Jian-Feng Feng and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature human behaviour, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Personality Genomics.Annual review of psychology · 2026
    Review
  3. Genetic and Cortical Cell-Type Liability Architecture of Autism.bioRxiv : the preprint server for biology · 2025
    Article
  4. Article
  5. Timing matters in olfaction.Nature human behaviour · 2024
    Article
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

12 authors.

Xin-Rui Wu *Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.ORCID 0000-0002-5160-538X
Ze-Yu Li *Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.ORCID 0009-0004-3412-0833
Liu Yang *Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
Ying Liu *Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
Chen-Jie FeiDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
Yue-Ting DengDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.ORCID 0000-0002-9962-7860
Wei-Shi LiuDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
Bang-Sheng WuDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
Qiang DongDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.ORCID 0000-0002-3874-0130
Jian-Feng FengInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.ORCID 0000-0001-5987-2258
Wei ChengDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. wcheng@fudan.edu.cn.ORCID 0000-0003-1118-1743
Jin-Tai YuDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. jintai_yu@fudan.edu.cn.ORCID 0000-0002-2532-383X

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81971032National Natural Science Foundation of China (National Science Foundation of China) 82071201National Natural Science Foundation of China (National Science Foundation of China) 82071997National Natural Science Foundation of China (National Science Foundation of China) 92249305
6 · The paper itself

Abstract

Existing genetic studies of neuroticism have been largely limited to common variants. Here we performed a large-scale exome analysis of white British individuals from UK Biobank, revealing the role of coding variants in neuroticism. For rare variants, collapsing analysis uncovered 14 neuroticism-associated genes. Among these, 12 (PTPRE, BCL10, TRIM32, ANKRD12, ADGRB2, MON2, HIF1A, ITGB2, STK39, CAPNS2, OGFOD1 and KDM4B) were novel, and the remaining (MADD and TRPC4AP) showed convergent evidence with common variants. Heritability of rare coding variants was estimated to be up to 7.3% for neuroticism. For common variants, we identified 78 significant associations, implicating 6 unreported genes. We subsequently replicated these variants using meta-analysis across other four ancestries from UK Biobank and summary data from 23andMe sample. Furthermore, these variants had widespread impacts on neuropsychiatric disorders, cognitive abilities and brain structure. Our findings deepen the understanding of neuroticism's genetic architecture and provide potential targets for future mechanistic research.

Indexed as

NeuroticismAdultAgedBiological Specimen BanksExome SequencingFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedUnited Kingdom

Identifiers

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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 OpenQuestion graph.