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Lookup NU author(s): Dr Sarah PickettORCiD, Professor Gavin Hudson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s).Neuroticism is a heritable trait composed of separate facets, each conferring different levels of protection or risk, to health. By examining mitochondrial DNA in 269,506 individuals, we show mitochondrial haplogroups explain 0.07-0.01% of variance in neuroticism and identify five haplogroup and 15 mitochondria-marker associations across a general factor of neuroticism, and two special factors of anxiety/tension, and worry/vulnerability with effect sizes of the same magnitude as autosomal variants. Within-haplogroup genome-wide association studies identified H-haplogroup-specific autosomal effects explaining 1.4% variance of worry/vulnerability. These H-haplogroup-specific autosomal effects show a pleiotropic relationship with cognitive, physical and mental health that differs from that found when assessing autosomal effects across haplogroups. We identify interactions between chromosome 9 regions and mitochondrial haplogroups at P < 5 × 10−8, revealing associations between general neuroticism and anxiety/tension with brain-specific gene co-expression networks. These results indicate that the mitochondrial genome contributes toward neuroticism and the autosomal links between neuroticism and health.
Author(s): Xia C, Pickett SJ, Liewald DCM, Weiss A, Hudson G, Hill WD
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2023
Volume: 14
Issue: 1
Online publication date: 30/05/2023
Acceptance date: 04/05/2023
Date deposited: 13/06/2023
ISSN (electronic): 2041-1723
Publisher: Nature Research
URL: https://doi.org/10.1038/s41467-023-38480-y
DOI: 10.1038/s41467-023-38480-y
Data Access Statement: UK Biobank data used in this study are available via the UK Biobank data access process (see http://www.ukbiobank.ac.uk/register-apply/). The Summary statistics for MT associations are available in Supplementary Data 4-6, Summary statistics for the autosomal associations are available through GWAS catalog at https://www.ebi.ac.uk/gwas/ under accession codes GCST90264121, GCST90264122, GCST90264123, GCST90264124, GCST90264125, GCST90264126, GCST90264127, GCST90264128, GCST90264129, GCST90264130, GCST90264131, GCST90264132, GCST90264133, GCST90264134, GCST90264135, GCST90264136, GCST90264137, GCST90264138, GCST90264139, GCST90264140, GCST90264141, GCST90264142, GCST90264143, GCST90264144, GCST90264145, GCST90264146, GCST90264147, GCST90264148, GCST90264149, and GCST90264150.
PubMed id: 37253732
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