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Chunk #24 — Results — Multiple cell types are independently associated with brain complex traits

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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease.
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Many neuronal cell types passed our stringent significance threshold for multiple brain traits (Figure 2A and S5). This could be because gene expression profiles are highly correlated across cell types and/or because many cell types are independently associated with the different traits. In order to address this, we performed univariate conditional analysis using MAGMA, testing whether cell type associations remained significant after controlling for the 10% most specific genes from other cell types (Table S6). We observed that multiple cell types were independently associated with age at menarche, anorexia, autism, bipolar, BMI, educational attainment, intelligence, MDD, neuroticism and schizophrenia (Figure S12). As in our previous study 12, we found that the association between schizophrenia and telencephalon projecting inhibitory neurons (i.e. medium spiny neurons) appears to be independent from telencephalon projecting excitatory neurons (i.e. pyramidal neurons). For Parkinson’s disease, we found that enteric neurons, oligodendrocytes and cholinergic and monoaminergic neurons were independently associated with the disorder (Figure 2B), suggesting that these three different cell types play an independent role in the etiology of the disorder.