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An augmented Mendelian randomization approach provides causality of brain imaging features on complex traits in a single biobank-scale dataset.
Yang, Anyi; Yang, Yucheng T; Zhao, Xing-Ming.
Afiliação
  • Yang A; Department of Neurology, Zhongshan Hospital and Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, People's Republic of China.
  • Yang YT; MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, People's Republic of China.
  • Zhao XM; Department of Neurology, Zhongshan Hospital and Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, People's Republic of China.
PLoS Genet ; 19(12): e1011112, 2023 Dec.
Article em En | MEDLINE | ID: mdl-38150468
ABSTRACT
Mendelian randomization (MR) is an effective approach for revealing causal risk factors that underpin complex traits and diseases. While MR has been more widely applied under two-sample settings, it is more promising to be used in one single large cohort given the rise of biobank-scale datasets that simultaneously contain genotype data, brain imaging data, and matched complex traits from the same individual. However, most existing multivariable MR methods have been developed for two-sample setting or a small number of exposures. In this study, we introduce a one-sample multivariable MR method based on partial least squares and Lasso regression (MR-PL). MR-PL is capable of considering the correlation among exposures (e.g., brain imaging features) when the number of exposures is extremely upscaled, while also correcting for winner's curse bias. We performed extensive and systematic simulations, and demonstrated the robustness and reliability of our method. Comprehensive simulations confirmed that MR-PL can generate more precise causal estimates with lower false positive rates than alternative approaches. Finally, we applied MR-PL to the datasets from UK Biobank to reveal the causal effects of 36 white matter tracts on 180 complex traits, and showed putative white matter tracts that are implicated in smoking, blood vascular function-related traits, and eating behaviors.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bancos de Espécimes Biológicos / Análise da Randomização Mendeliana Limite: Humans Idioma: En Revista: PLoS Genet Assunto da revista: GENETICA Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bancos de Espécimes Biológicos / Análise da Randomização Mendeliana Limite: Humans Idioma: En Revista: PLoS Genet Assunto da revista: GENETICA Ano de publicação: 2023 Tipo de documento: Article