Wellbeing and brain structure: A comprehensive phenotypic and genetic study of image-derived phenotypes in the UK Biobank

Javad Jamshidi; Haeme R P Park; Arthur Montalto; Janice M Fullerton; Justine M Gatt

doi:10.1002/hbm.25993

Wellbeing and brain structure: A comprehensive phenotypic and genetic study of image-derived phenotypes in the UK Biobank

Hum Brain Mapp. 2022 Dec 1;43(17):5180-5193. doi: 10.1002/hbm.25993. Epub 2022 Jun 29.

Authors

Javad Jamshidi^{1

2}, Haeme R P Park^{1

2}, Arthur Montalto^{1

2}, Janice M Fullerton^{1

3}, Justine M Gatt^{1

2}

Affiliations

¹ Neuroscience Research Australia, Sydney, New South Wales, Australia.
² School of Psychology, University of New South Wales, Sydney, New South Wales, Australia.
³ School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.

Abstract

Wellbeing, an important component of mental health, is influenced by genetic and environmental factors. Previous association studies between brain structure and wellbeing have typically focused on volumetric measures and employed small cohorts. Using the UK Biobank Resource, we explored the relationships between wellbeing and brain morphometrics (volume, thickness and surface area) at both phenotypic and genetic levels. The sample comprised 38,982 participants with neuroimaging and wellbeing phenotype data, of which 19,234 had genotypes from which wellbeing polygenic scores (PGS) were calculated. We examined the association of wellbeing phenotype and PGS with all brain regions (including cortical, subcortical, brainstem and cerebellar regions) using multiple linear models, including (1) basic neuroimaging covariates and (2) additional demographic factors that may synergistically impact wellbeing and its neural correlates. Genetic correlations between genomic variants influencing wellbeing and brain structure were also investigated. Small but significant associations between wellbeing and volumes of several cerebellar structures (β = 0.015-0.029, P_FDR = 0.007-3.8 × 10^-9 ), brainstem, nucleus accumbens and caudate were found. Cortical associations with wellbeing included volume of right lateral occipital, thickness of bilateral lateral occipital and cuneus, and surface area of left superior parietal, supramarginal and pre-/post-central regions. Wellbeing-PGS was associated with cerebellar volumes and supramarginal surface area. Small mediation effects of wellbeing phenotype and PGS on right VIIIb cerebellum were evident. No genetic correlation was found between wellbeing and brain morphometric measures. We provide a comprehensive overview of wellbeing-related brain morphometric variation. Notably, small effect sizes reflect the multifaceted nature of this concept.

Keywords: cerebellum; cortex; magnetic resonance imaging; mediation; polygenic score; subcortical; wellbeing.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Biological Specimen Banks*
Brain / diagnostic imaging
Magnetic Resonance Imaging* / methods
Phenotype
United Kingdom

Abstract

Publication types

MeSH terms

Grants and funding