| Autor: |
Grosjean I; University Côte d'Azur, CNRS, INSERM, IRCAN, FHU-OncoAge, Centre Antoine Lacassagne, France., Roméo B; University Côte d'Azur, CNRS, INSERM, IRCAN, FHU-OncoAge, Centre Antoine Lacassagne, France., Domdom MA; University Côte d'Azur, CNRS, INSERM, IRCAN, FHU-OncoAge, Centre Antoine Lacassagne, France., Belaid A; Université Côte d'Azur (UCA), INSERM U1065, C3M, Team 5, F-06204, France., D'Andréa G; University Côte d'Azur, CNRS, INSERM, IRCAN, FHU-OncoAge, Centre Antoine Lacassagne, France.; ENT and Head and Neck surgery department, Institut Universitaire de la Face et du Cou, CHU de Nice, University Hospital, Côte d'Azur University, Nice, France., Guillot N; University Côte d'Azur, CNRS, INSERM, IRCAN, FHU-OncoAge, Centre Antoine Lacassagne, France., Gherardi RK; INSERM U955 Team Relais, Faculty of Health, Paris Est University, France., Gal J; University Côte d'Azur, Centre Antoine Lacassagne, Epidemiology and Biostatistics Department, Nice, France., Milano G; Université Côte d'Azur, Centre Antoine Lacassagne, UPR7497, Nice, France., Marquette CH; University Côte d'Azur, CNRS, INSERM, IRCAN, FHU-OncoAge, Centre Antoine Lacassagne, France.; University Côte d'Azur, FHU-OncoAge, Department of Pulmonary Medicine and Oncology, CHU de Nice, Nice, France., Hung RJ; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada; Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada., Landi MT; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Han Y; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA., Brest P; University Côte d'Azur, CNRS, INSERM, IRCAN, FHU-OncoAge, Centre Antoine Lacassagne, France., Von Bergen M; Helmholtz Centre for Environmental Research GmbH - UFZ, Dep. of Molecular Systems Biology; University of Leipzig, Faculty of Life Sciences, Institute of Biochemistry, Leipzig, Germany., Klionsky DJ; University of Michigan, Life Sciences Institute, Ann Arbor, MI, 48109, USA., Amos CI; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA., Hofman P; University Côte d'Azur, CNRS, INSERM, IRCAN, FHU-OncoAge, Centre Antoine Lacassagne, France.; University Côte d'Azur, FHU-OncoAge, CHU de Nice, Laboratory of Clinical and Experimental Pathology (LPCE) Biobank (BB-0033-00025), Nice, France., Mograbi B; University Côte d'Azur, CNRS, INSERM, IRCAN, FHU-OncoAge, Centre Antoine Lacassagne, France. |
| Abstrakt: |
At a time when complex diseases affect globally 280 million people and claim 14 million lives every year, there is an urgent need to rapidly increase our knowledge into their underlying etiologies. Though critical in identifying the people at risk, the causal environmental factors (microbiome and/or pollutants) and the affected pathophysiological mechanisms are not well understood. Herein, we consider the variations of autophagy-related ( ATG ) genes at the heart of mechanisms of increased susceptibility to environmental stress. A comprehensive autophagy genomic resource is presented with 263 single nucleotide polymorphisms (SNPs) for 69 autophagy-related genes associated with 117 autoimmune, inflammatory, infectious, cardiovascular, neurological, respiratory, and endocrine diseases. We thus propose the term 'autophagopathies' to group together a class of complex human diseases the etiology of which lies in a genetic defect of the autophagy machinery, whether directly related or not to an abnormal flux in autophagy, LC3-associated phagocytosis, or any associated trafficking. The future of precision medicine for common diseases will lie in our ability to exploit these ATG SNP x environment relationships to develop new polygenetic risk scores, new management guidelines, and optimal therapies for afflicted patients. Abbreviations: ATG, autophagy-related; ALS-FTD, amyotrophic lateral sclerosis-frontotemporal dementia; ccRCC, clear cell renal cell carcinoma; CD, Crohn disease; COPD, chronic obstructive pulmonary disease; eQTL, expression quantitative trait loci; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous cell carcinoma; GTEx, genotype-tissue expression; GWAS, genome-wide association studies; LAP, LC3-associated phagocytosis; LC3-II, phosphatidylethanolamine conjugated form of LC3; LD, linkage disequilibrium; LUAD, lung adenocarcinoma; MAF, minor allele frequency; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NSCLC, non-small cell lung cancer; OS, overall survival; PtdIns3K CIII, class III phosphatidylinositol 3 kinase; PtdIns3P, phosphatidylinositol-3-phosphate; SLE, systemic lupus erythematosus; SNPs, single-nucleotide polymorphisms; mQTL, methylation quantitative trait loci; ULK, unc-51 like autophagy activating kinase; UTRs, untranslated regions; WHO, World Health Organization. |
