ArticleNature communications2024
Whole-exome sequencing identifies protein-coding variants associated with brain iron in 29,828 individuals.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Neurobehavioural genes exert indirect genetic effects on blood lipid profiles through behavioural traits.Communications biology · 2026Article
- Cognitive implications and associated transcriptomic signatures of distinct regional iron depositions in cerebral small vessel disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Large-scale exome sequencing identified 18 novel genes for neuroticism in 394,005 UK-based individuals.Nature human behaviour · 2025Article
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Authors and funding
14 authors.
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Abstract
Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across 26 brain regions among 26,789 UK Biobank participants. We find 36 genes linked to brain iron, with 29 not being previously reported, and 16 of them can be replicated in an independent dataset with 3,039 subjects. Many of these genes are involved in iron transport and homeostasis, such as FTH1 and MLX. Several genes, while not previously connected to brain iron, are associated with iron-related brain disorders like Parkinson's (STAB1, KCNA10), Alzheimer's (SHANK1), and depression (GFAP). Mendelian randomization analysis reveals six causal relationships from regional brain iron to brain disorders, such as from the hippocampus to depression and from the substantia nigra to Parkinson's. These insights advance our understanding of the genetic architecture of brain iron and offer potential therapeutic targets for brain disorders.
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