Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases
Creators: name: Grosjean, Iris
name: Roméo, Barnabé
name: Domdom, Marie-Angela
name: Belaid, Amine
name: D’Andréa, Grégoire
name: Guillot, Nicolas
name: Gherardi, Romain K
name: Gal, Jocelyn
name: Milano, Gérard
name: Marquette, Charles Hugo
name: Hung, Rayjean J.
name: Landi, Maria Teresa
name: Han, Younghun
name: Brest, Patrick
name: Von Bergen, Martin
name: Klionsky, Daniel J.
name: Amos, Christopher I.
name: Hofman, Paul
name: Mograbi, Baharia
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Physiology
subject: Immunology
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: 110309 Infectious Diseases
subject: FOS: Health sciences

description: 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 (<i>ATG</i>) 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 <i>ATG</i> SNP x environment relationships to develop new polygenetic risk scores, new management guidelines, and optimal therapies for afflicted patients. <b>Abbreviations:</b> 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.