Cargando…

Human genetics uncovers MAP3K15 as an obesity-independent therapeutic target for diabetes

We performed collapsing analyses on 454,796 UK Biobank (UKB) exomes to detect gene-level associations with diabetes. Recessive carriers of nonsynonymous variants in MAP3K15 were 30% less likely to develop diabetes (P = 5.7 × 10(−10)) and had lower glycosylated hemoglobin (β = −0.14 SD units, P = 1.1...

Descripción completa

Detalles Bibliográficos
Autores principales:	Nag, Abhishek, Dhindsa, Ryan S., Mitchell, Jonathan, Vasavda, Chirag, Harper, Andrew R., Vitsios, Dimitrios, Ahnmark, Andrea, Bilican, Bilada, Madeyski-Bengtson, Katja, Zarrouki, Bader, Zoghbi, Anthony W., Wang, Quanli, Smith, Katherine R., Alegre-Díaz, Jesus, Kuri-Morales, Pablo, Berumen, Jaime, Tapia-Conyer, Roberto, Emberson, Jonathan, Torres, Jason M., Collins, Rory, Smith, David M., Challis, Benjamin, Paul, Dirk S., Bohlooly-Y, Mohammad, Snowden, Mike, Baker, David, Fritsche-Danielson, Regina, Pangalos, Menelas N., Petrovski, Slavé
Formato:	Online Artículo Texto
Lenguaje:	English
Publicado:	American Association for the Advancement of Science 2022
Materias:	Biomedicine and Life Sciences
Acceso en línea:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668288/ https://www.ncbi.nlm.nih.gov/pubmed/36383675 http://dx.doi.org/10.1126/sciadv.add5430

Ejemplares similares

Prioritizing non-coding regions based on human genomic constraint and sequence context with deep learning
por: Vitsios, Dimitrios, et al.
Publicado: (2021)

Rare variant associations with plasma protein levels in the UK Biobank
por: Dhindsa, Ryan S., et al.
Publicado: (2023)

Cancer-driving mutations are enriched in genic regions intolerant to germline variation
por: Vitsios, Dimitrios, et al.
Publicado: (2022)

Effects of protein-coding variants on blood metabolite measurements and clinical biomarkers in the UK Biobank
por: Nag, Abhishek, et al.
Publicado: (2023)

Mantis-ml: Disease-Agnostic Gene Prioritization from High-Throughput Genomic Screens by Stochastic Semi-supervised Learning
por: Vitsios, Dimitrios, et al.
Publicado: (2020)

Gene-SCOUT: identifying genes with similar continuous trait fingerprints from phenome-wide association analyses
por: Middleton, Lawrence, et al.
Publicado: (2022)

The prevalence of chronic diseases and major disease risk factors at different ages among 150 000 men and women living in Mexico City: cross-sectional analyses of a prospective study
por: Kuri-Morales, Pablo, et al.
Publicado: (2009)

DrugnomeAI is an ensemble machine-learning framework for predicting druggability of candidate drug targets
por: Raies, Arwa, et al.
Publicado: (2022)

Author Correction: DrugnomeAI is an ensemble machine-learning framework for predicting druggability of candidate drug targets
por: Raies, Arwa, et al.
Publicado: (2023)

Correction: Orion: Detecting regions of the human non-coding genome that are intolerant to variation using population genetics
por: Gussow, Ayal B., et al.
Publicado: (2018)

Orion: Detecting regions of the human non-coding genome that are intolerant to variation using population genetics
por: Gussow, Ayal B., et al.
Publicado: (2017)

Rare variant contribution to human disease in 281,104 UK Biobank exomes
por: Wang, Quanli, et al.
Publicado: (2021)

Adiposity and Blood Pressure in 110 000 Mexican Adults
por: Gnatiuc, Louisa, et al.
Publicado: (2017)

Body Composition and Risk of Vascular‐Metabolic Mortality Risk in 113 000 Mexican Men and Women Without Prior Chronic Disease
por: Gnatiuc Friedrichs, Louisa, et al.
Publicado: (2023)

Association of Blood Pressure With Cause-Specific Mortality in Mexican Adults
por: Tapia-Conyer, Roberto, et al.
Publicado: (2020)

Correction: Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes
por: Petrovski, Slavé, et al.
Publicado: (2013)

The intolerance to functional genetic variation of protein domains predicts the localization of pathogenic mutations within genes
por: Gussow, Ayal B., et al.
Publicado: (2016)

Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes
por: Petrovski, Slavé, et al.
Publicado: (2013)

Changes in the Diagnosis and Management of Diabetes in Mexico City Between 1998–2004 and 2015–2019
por: Aguilar-Ramirez, Diego, et al.
Publicado: (2021)

Body mass index and COVID-19 mortality: prospective study of 120 000 Mexican adults
por: Alegre-Díaz, Jesus, et al.
Publicado: (2022)

Unpicking neurodegeneration in a dish with human pluripotent stem cells: One cell type at a time
por: Bilican, Bilada, et al.
Publicado: (2013)

Induction of Olig2(+) Precursors by FGF Involves BMP Signalling Blockade at the Smad Level
por: Bilican, Bilada, et al.
Publicado: (2008)

Diabetes and infectious disease mortality in Mexico City
por: Bragg, Fiona, et al.
Publicado: (2023)

Effect of diabetes duration and glycaemic control on 14-year cause-specific mortality in Mexican adults: a blood-based prospective cohort study
por: Herrington, William G, et al.
Publicado: (2018)

Association of Kidney Function With NMR-Quantified Lipids, Lipoproteins, and Metabolic Measures in Mexican Adults
por: Aguilar-Ramirez, Diego, et al.
Publicado: (2021)

Abdominal and gluteo-femoral markers of adiposity and risk of vascular-metabolic mortality in a prospective study of 150 000 Mexican adults
por: Gnatiuc, Louisa, et al.
Publicado: (2021)

Low-intensity daily smoking and cause-specific mortality in Mexico: prospective study of 150 000 adults
por: Thomson, Blake, et al.
Publicado: (2021)

Adiposity and NMR-measured lipid and metabolic biomarkers among 30,000 Mexican adults
por: Aguilar-Ramirez, Diego, et al.
Publicado: (2022)

Educational and social inequalities and cause-specific mortality: a prospective study in two municipalities of Mexico City
por: Addey, Thomas, et al.
Publicado: (2023)

The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity
por: Petrovski, Slavé, et al.
Publicado: (2015)

Optimizing genomic medicine in epilepsy through a gene-customized approach to missense variant interpretation
por: Traynelis, Joshua, et al.
Publicado: (2017)

Unequal representation of genetic variation across ancestry groups creates healthcare inequality in the application of precision medicine
por: Petrovski, Slavé, et al.
Publicado: (2016)

Identification of a missense variant in SPDL1 associated with idiopathic pulmonary fibrosis
por: Dhindsa, Ryan S., et al.
Publicado: (2021)

Pnpla3 silencing with antisense oligonucleotides ameliorates nonalcoholic steatohepatitis and fibrosis in Pnpla3 I148M knock-in mice
por: Lindén, Daniel, et al.
Publicado: (2019)

High Yields of Oligodendrocyte Lineage Cells from Human Embryonic Stem Cells at Physiological Oxygen Tensions for Evaluation of Translational Biology
por: Stacpoole, Sybil R.L., et al.
Publicado: (2013)

Decoding non-random mutational signatures at Cas9 targeted sites
por: Taheri-Ghahfarokhi, Amir, et al.
Publicado: (2018)

Genotyping, sequencing and analysis of 140,000 adults from Mexico City
por: Ziyatdinov, Andrey, et al.
Publicado: (2023)

MTR-Viewer: identifying regions within genes under purifying selection
por: Silk, Michael, et al.
Publicado: (2019)

Physiological Normoxia and Absence of EGF Is Required for the Long-Term Propagation of Anterior Neural Precursors from Human Pluripotent Cells
por: Bilican, Bilada, et al.
Publicado: (2014)

meaRtools: An R package for the analysis of neuronal networks recorded on microelectrode arrays
por: Gelfman, Sahar, et al.
Publicado: (2018)

Cannot write session to /tmp/vufind_sessions/sess_7283tvs4fta74mq0bh4njph9nt