Functional variants identify sex-specific genes and pathways in Alzheimer's Disease.

Autor: Bourquard T; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Lee K; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Al-Ramahi I; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, 77030, USA.; Center for Alzheimer's and Neurodegenerative Diseases, Baylor College of Medicine, Houston, TX, 77030, USA., Pham M; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Shapiro D; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Lagisetty Y; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Biology and Pharmacology, UTHealth McGovern Medical School, Houston, TX, 77030, USA., Soleimani S; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Mota S; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Wilhelm K; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Samieinasab M; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Kim YW; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Huh E; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Asmussen J; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Katsonis P; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Botas J; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, 77030, USA.; Center for Alzheimer's and Neurodegenerative Diseases, Baylor College of Medicine, Houston, TX, 77030, USA., Lichtarge O; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. lichtarg@bcm.edu.; Center for Alzheimer's and Neurodegenerative Diseases, Baylor College of Medicine, Houston, TX, 77030, USA. lichtarg@bcm.edu.; Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, TX, 77030, USA. lichtarg@bcm.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 13; Vol. 14 (1), pp. 2765. Date of Electronic Publication: 2023 May 13.
DOI: 10.1038/s41467-023-38374-z
Abstrakt: The incidence of Alzheimer's Disease in females is almost double that of males. To search for sex-specific gene associations, we build a machine learning approach focused on functionally impactful coding variants. This method can detect differences between sequenced cases and controls in small cohorts. In the Alzheimer's Disease Sequencing Project with mixed sexes, this approach identified genes enriched for immune response pathways. After sex-separation, genes become specifically enriched for stress-response pathways in male and cell-cycle pathways in female. These genes improve disease risk prediction in silico and modulate Drosophila neurodegeneration in vivo. Thus, a general approach for machine learning on functionally impactful variants can uncover sex-specific candidates towards diagnostic biomarkers and therapeutic targets.
(© 2023. The Author(s).)
Databáze: MEDLINE
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