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EBioMedicine ; 74: 103732, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34864363


BACKGROUND: The survival time of amyotrophic lateral sclerosis (ALS) is greatly variable and protective or risk effects of the potential survival predictors are controversial. Thus, we aim to undertake a comprehensive meta-analysis of studies investigating non-genetic prognostic and survival factors in patients with ALS. METHODS: A search of relevant literature from PubMed, Embase, Cochrane library and other citations from 1st January 1966 to 1st December 020 was conducted. Random-effects models were conducted to pool the multivariable or adjusted hazard ratios (HR) by Stata MP 16.0. PROSPERO registration number: CRD42021256923. FINDINGS: A total of 5717 reports were identified, with 115 studies meeting pre-designed inclusion criteria involving 55,169 ALS patients. Five dimensions, including demographic, environmental or lifestyle, clinical manifestations, biochemical index, therapeutic factors or comorbidities were investigated. Twenty-five prediction factors, including twenty non-intervenable and five intervenable factors, were associated with ALS survival. Among them, NFL (HR:3.70, 6.80, in serum and CSF, respectively), FTD (HR:2.98), ALSFRS-R change (HR:2.37), respiratory subtype (HR:2.20), executive dysfunction (HR:2.10) and age of onset (HR:1.03) were superior predictors for poor prognosis, but pLMN or pUMN (HR:0.32), baseline ALSFRS-R score (HR:0.95), duration (HR:0.96), diagnostic delay (HR:0.97) were superior predictors for a good prognosis. Our results did not support the involvement of gender, education level, diabetes, hypertension, NIV, gastrostomy, and statins in ALS survival. INTERPRETATION: Our study provided a comprehensive and quantitative index for assessing the prognosis for ALS patients, and the identified non-intervenable or intervenable factors will facilitate the development of treatment strategies for ALS. FUNDING: This study was supported by the National Natural Science Fund of China (Grant No. 81971188), the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (Grant No. 2019HXFH046), and the Science and Technology Bureau Fund of Sichuan Province (No. 2019YFS0216).

Esclerose Amiotrófica Lateral/mortalidade , Feminino , Humanos , Estilo de Vida , Masculino , Prognóstico , Medição de Risco , Análise de Sobrevida , Adulto Jovem
BMC Med ; 19(1): 27, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33541344


BACKGROUND: Epidemiological and clinical studies have suggested comorbidity between amyotrophic lateral sclerosis (ALS) and autoimmune disorders. However, little is known about their shared genetic architecture. METHODS: To examine the relation between ALS and 10 autoimmune diseases, including asthma, celiac disease (CeD), Crohn's disease (CD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and ulcerative colitis (UC), and identify shared risk loci, we first estimated the genetic correlation using summary statistics from genome-wide association studies, and then analyzed the genetic enrichment leveraging the conditional false discovery rate statistical method. RESULTS: We identified a significant positive genetic correlation between ALS and CeD, MS, RA, and SLE, as well as a significant negative genetic correlation between ALS and IBD, UC, and CD. Robust genetic enrichment was observed between ALS and CeD and MS, and moderate enrichment was found between ALS and UC and T1D. Thirteen shared genetic loci were identified, among which five were suggestively significant in another ALS GWAS, namely rs3828599 (GPX3), rs3849943 (C9orf72), rs7154847 (G2E3), rs6571361 (SCFD1), and rs9903355 (GGNBP2). By integrating cis-expression quantitative trait loci analyses in Braineac and GTEx, we further identified GGNBP2, ATXN3, and SLC9A8 as novel ALS risk genes. Functional enrichment analysis indicated that the shared risk genes were involved in four pathways including membrane trafficking, vesicle-mediated transport, ER to Golgi anterograde transport, and transport to the Golgi and subsequent modification. CONCLUSIONS: Our findings demonstrate a specific genetic correlation between ALS and autoimmune diseases and identify shared risk loci, including three novel ALS risk genes. These results provide a better understanding for the pleiotropy of ALS and have implications for future therapeutic trials.

Esclerose Amiotrófica Lateral/genética , Doenças Autoimunes/genética , Estudo de Associação Genômica Ampla , Artrite Reumatoide/genética , Doença Celíaca/genética , Colite Ulcerativa/genética , Doença de Crohn/genética , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Humanos , Lúpus Eritematoso Sistêmico/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Locos de Características Quantitativas