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GWAS Study

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

Wu XR, Li ZY, Yang L et al.

39511343 PubMed ID
GWAS Study Type
394005 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

WX
Wu XR
LZ
Li ZY
YL
Yang L
LY
Liu Y
FC
Fei CJ
DY
Deng YT
LW
Liu WS
WB
Wu BS
DQ
Dong Q
FJ
Feng JF
CW
Cheng W
YJ
Yu JT
Chapter II

Abstract

Summary of the research findings

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.

155,119 British ancestry cases, 193,273 British ancestry controls

Chapter III

Study Statistics

Key metrics and study information

394005
Total Participants
GWAS
Study Type
Yes
Replicated
25,376 European ancestry individuals, 8,019 Asian / Asian British ancestry individuals, 6,453 Black / Black British ancestry individuals, 5,765 Admixed or unknown ancestry individuals
Replication Participants
European, Asian unspecified, African unspecified, Other admixed ancestry, NR
Ancestry
U.K.
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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Analysis In Progress

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