Linjing Zhang1, Lu Tang1, Tao Huang2,3, Dongsheng Fan1,4. 1. Department of Neurology, Peking University Third Hospital, Beijing, China. 2. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. 3. Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, China. 4. Key Laboratory for Neuroscience, National Health Commission/Ministry of Education, Peking University, Beijing, China.
Abstract
OBJECTIVE: Observational studies have indicated that life course adiposity is associated with amyotrophic lateral sclerosis (ALS). However, whether such an association reflects causality remains unclear. We aimed to determine whether life course adiposity such as birth weight (BW), childhood body mass index (BMI), adult BMI, body fat percentage (BF%), and waist-to-hip ratio (WHR) have causal effects on ALS. METHODS: Single nucleotide polymorphisms (SNPs) significantly associated with life course adiposity were used as instrumental variables to estimate the causal effects on ALS. We used summary-level data from a cohort of 20,806 cases and 59,804 controls in a Mendelian randomization (MR) framework. RESULTS: Genetically predicted one standard deviation (1-SD) increase in BF% was associated with lower risk of ALS (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.54-0.83, p = 3.25E-04) after Bonferroni correction (p < 0.05/5). Genetically predicted 1-SD higher childhood BMI was suggestively associated with lower risk of ALS (OR = 0.88, 95% CI = 0.78-0.99, p = 0.031). The weighted median method indicated a suggestive association between BMI and ALS (OR = 0.86, 95% CI = 0.69-0.96, p = 0.016). Neither a genetically predicted 1-SD increase in BW (inverse variance weighted [IVW]: OR = 1.01, 95% CI = 0.87-1.17, p = 0.939) nor WHR adjusted for BMI (IVW: OR = 0.90, 95% CI = 0.76-1.05, p = 0.178) was associated with ALS. INTERPRETATION: Our findings provide novel evidence supporting a causal role of higher adiposity, taken as a whole, on lower risk of ALS. A deeper understanding of the energy metabolism of ALS is more likely to identify feasible nutritional interventions and even novel therapeutic targets that might improve the survival of ALS patients. Ann Neurol 2020;87:434-441.
OBJECTIVE: Observational studies have indicated that life course adiposity is associated with amyotrophic lateral sclerosis (ALS). However, whether such an association reflects causality remains unclear. We aimed to determine whether life course adiposity such as birth weight (BW), childhood body mass index (BMI), adult BMI, body fat percentage (BF%), and waist-to-hip ratio (WHR) have causal effects on ALS. METHODS: Single nucleotide polymorphisms (SNPs) significantly associated with life course adiposity were used as instrumental variables to estimate the causal effects on ALS. We used summary-level data from a cohort of 20,806 cases and 59,804 controls in a Mendelian randomization (MR) framework. RESULTS: Genetically predicted one standard deviation (1-SD) increase in BF% was associated with lower risk of ALS (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.54-0.83, p = 3.25E-04) after Bonferroni correction (p < 0.05/5). Genetically predicted 1-SD higher childhood BMI was suggestively associated with lower risk of ALS (OR = 0.88, 95% CI = 0.78-0.99, p = 0.031). The weighted median method indicated a suggestive association between BMI and ALS (OR = 0.86, 95% CI = 0.69-0.96, p = 0.016). Neither a genetically predicted 1-SD increase in BW (inverse variance weighted [IVW]: OR = 1.01, 95% CI = 0.87-1.17, p = 0.939) nor WHR adjusted for BMI (IVW: OR = 0.90, 95% CI = 0.76-1.05, p = 0.178) was associated with ALS. INTERPRETATION: Our findings provide novel evidence supporting a causal role of higher adiposity, taken as a whole, on lower risk of ALS. A deeper understanding of the energy metabolism of ALS is more likely to identify feasible nutritional interventions and even novel therapeutic targets that might improve the survival of ALSpatients. Ann Neurol 2020;87:434-441.
Authors: Juan Miguel Godoy-Corchuelo; Luis C Fernández-Beltrán; Zeinab Ali; María J Gil-Moreno; Juan I López-Carbonero; Antonio Guerrero-Sola; Angélica Larrad-Sainz; Jorge Matias-Guiu; Jordi A Matias-Guiu; Thomas J Cunningham; Silvia Corrochano Journal: Biomedicines Date: 2022-05-10
Authors: Noelia Esteban-García; Luis C Fernández-Beltrán; Juan Miguel Godoy-Corchuelo; Jose L Ayala; Jordi A Matias-Guiu; Silvia Corrochano Journal: Front Aging Neurosci Date: 2022-03-25 Impact factor: 5.750