The contributions of mitochondrial and nuclear mitochondrial genetic variation to neuroticism

Charley Xia, Sarah J. Pickett, David C.M. Liewald, Alexander Weiss, Gavin Hudson, W. David Hill*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article number3146
JournalNature Communications
Issue number1
Early online date30 May 2023
Publication statusPublished - May 2023


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