ArticleBiological psychiatry. Cognitive neuroscience and neuroimaging2022
Genomic Studies Across the Lifespan Point to Early Mechanisms Determining Subcortical Volumes.
Article in Biological psychiatry. Cognitive neuroscience and neuroimaging, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.Nature aging · 2025Article
- Mapping Divergent Subfield-Specific Hippocampal Degeneration in Mild Cognitive Impairment Continuum: Volumetric, Cognitive, and Genetic Predictors of Accelerated Hippocampal Biological Aging.CNS neuroscience & therapeutics · 2025Article
- Exploring the molecular basis of the genetic correlation between body mass index and brain morphological traits.PLoS genetics · 2025Article
- Common genetic variation associated with adult subcortical brain volume is also associated with subcortical brain volume at birth.Frontiers in neuroscience · 2025Article
- Identification of novel candidate loci for Alzheimer's disease and related dementias by leveraging the shared genetic basis with hippocampal volume.Aging brain · 2025Article
- Diffusion imaging genomics provides novel insight into early mechanisms of cerebral small vessel disease.Molecular psychiatry · 2024Article
- Integration of estimated regional gene expression with neuroimaging and clinical phenotypes at biobank scale.PLoS biology · 2024Article
- Heritability of Subcortical Grey Matter Structures.Medicina (Kaunas, Lithuania) · 2022Article
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Authors and funding
22 authors at 13 institutions in 4 countries.
Funding
Abstract
backgroundSubcortical brain structures play a key role in pathological processes of age-related neurodegenerative disorders. Mounting evidence also suggests that early-life factors may have an impact on the development of common late-life neurological diseases, including genetic factors that can influence both brain maturation and neurodegeneration.
methodsUsing large population-based brain imaging datasets across the lifespan (N ≤ 40,628), we aimed to 1) estimate the heritability of subcortical volumes in young (18-35 years), middle (35-65 years), and older (65+ years) age, and their genetic correlation across age groups; 2) identify whether genetic loci associated with subcortical volumes in older persons also show associations in early adulthood, and explore underlying genes using transcriptome-wide association studies; and 3) explore their association with neurological phenotypes.
resultsHeritability of subcortical volumes consistently decreased with increasing age. Genetic risk scores for smaller caudate nucleus, putamen, and hippocampus volume in older adults were associated with smaller volumes in young adults. Individually, 10 loci associated with subcortical volumes in older adults also showed associations in young adults. Within these loci, transcriptome-wide association studies showed that expression of several genes in brain tissues (especially MYLK2 and TUFM) was associated with subcortical volumes in both age groups. One risk variant for smaller caudate nucleus volume (TUFM locus) was associated with lower cognitive performance. Genetically predicted Alzheimer's disease was associated with smaller subcortical volumes in middle and older age.
conclusionsOur findings provide novel insights into the genetic determinants of subcortical volumes across the lifespan. More studies are needed to decipher the underlying biology and clinical impact.
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