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- Title
The contributions of mitochondrial and nuclear mitochondrial genetic variation to neuroticism.
- Authors
Xia, Charley; Pickett, Sarah J.; Liewald, David C. M.; Weiss, Alexander; Hudson, Gavin; Hill, W. David
- Abstract
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. Genetic variation in mitochondrial DNA can influence human traits, but it is not as well studied in association with complex traits. Here, the authors find associations between mitochondrial haplogroups and genetic variation and neuroticism.
- Subjects
GENETIC variation; NEUROTICISM; GENOME-wide association studies; HAPLOGROUPS; GENE regulatory networks; PHYSIOLOGICAL stress; MITOCHONDRIAL DNA; MITOCHONDRIA
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-38480-y