Shared Genetic Links Between Amyotrophic Lateral Sclerosis and Obesity-Related Traits: A Genome-Wide Association Study

Li, Chunyu; Ou, Ruwei; Gu, Xiaojing; Wei, Qianqian; Shang, Huifang

doi:10.21203/rs.3.rs-50516/v1

Cited by 5 publications

(4 citation statements)

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“…These findings suggest that ALS status is a major determinant of energy metabolism. One possibility is that metabolites correlate with fat mass loss in ALS patients, 57 an idea supported by studies where ALS polygenic risk associates with body fat percentage in addition to BMI 58,59 . Interestingly, neither creatine nor creatinine were among the metabolites correlating with BMI change or diagnosis BMI, indicating weight changes may be more pronounced for fat mass than muscle mass.…”

Section: Discussionmentioning

confidence: 99%

Body mass index associates with amyotrophic lateral sclerosis survival and metabolomic profiles

et al. 2022

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Introduction/Aims: Body mass index (BMI) is linked to amyotrophic lateral sclerosis (ALS) risk and prognosis, but additional research is needed. The aim of this study was to identify whether and when historical changes in BMI occurred in ALS participants, how these longer term trajectories associated with survival, and whether metabolomic profiles provided insight into potential mechanisms.Methods: ALS and control participants self-reported body height and weight 10 (reference) and 5 years earlier, and at study entry (diagnosis for ALS participants). Generalized estimating equations evaluated differences in BMI trajectories between cases and controls. ALS survival was evaluated by BMI trajectory group using accelerated failure time models. BMI trajectories and survival associations were explored using published metabolomic profiling and correlation networks.Results: Ten-year BMI trends differed between ALS and controls, with BMI loss in the 5 years before diagnosis despite BMI gains 10 to 5 years beforehand in both groups. An overall 10-year drop in BMI associated with a 27.1% decrease in ALS survival (P = .010). Metabolomic networks in ALS participants showed dysregulation in sphingomyelin, bile acid, and plasmalogen subpathways.Discussion: ALS participants lost weight in the 5-year period before enrollment. BMI trajectories had three distinct groups and the group with significant weight loss in the past 10 years had the worst survival. Participants with a high BMI and increase in weight in the 10 years before symptom onset also had shorter survival. Certain metabolomics profiles were associated with the BMI trajectories. Replicating these findings in prospective cohorts is warranted.

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Section: Discussionmentioning

confidence: 99%

Body mass index associates with amyotrophic lateral sclerosis survival and metabolomic profiles

et al. 2022

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“…The copyright holder for this preprint this version posted December 9, 2022. ; https://doi.org/10.1101/2022.12.07.22283195 doi: medRxiv preprint study has identified that GGNBP2 is a shared genetic loci for ALS and obesity related traits, and associated with BMI and waist-hip ratio 94 . We first discovered the biological relationship between GGNBP2 and the two traits.…”

Section: Discussionmentioning

confidence: 99%

Investigating shared genetic architecture between obesity and multiple sclerosis

Zeng

Jiang

Huang

et al. 2022

Preprint

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Background and aims Observational studies have suggested a complex relationship between obesity and multiple sclerosis (MS). However, the role of genetic factors in the comorbidity and whether obesity exist consistent shared genetic relationships with MS, remains unclear. Our study aims to investigate the extent of shared genetic architecture underlying obesity and MS. Methods Based on genome-wide association studies (GWAS) summary statistics, we investigate the genetic correlation by the linkage disequilibrium score regression (LDSC) and genetic covariance analyzer (GNOVA). The casualty was identified by using bidirectional Mendelian randomization. Linkage disequilibrium score regression in specifically expressed genes (LDSC-SEG) and multi-marker analysis of GenoMic annotation (MAGMA) were utilized to investigate single-nucleotide polymorphisms (SNP) enrichment in the tissue and cell-type levels. We then identified shared risk SNPs using cross-trait meta-analyses and Heritability Estimation from Summary Statistics (ρ-HESS). We further explore the potential functional genes for BMI and MS using summary-data-based Mendelian randomization (SMR). Result We found significantly positive genetic correlation and 18 novel shared genetic SNPs were identified in cross-trait meta-analyses. We found the causality of BMI on MS using Mendelian randomization, but slight inconsistent evidence for the causality of MS on BMI. We observed tissue-specific level SNP heritability enrichment for BMI in 9 tissues and MS in 4 tissues, and in cell-type-specific level SNP heritability enrichment 12 consistent cell types were identified for BMI and MS in brain, spleen, lung and whole blood. Conclusion Our study identifies the genetical correlation and shared risk SNPs between BMI and MS. These findings could provide new insights into the etiology of comorbidity and have implications for future therapeutic trials.

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“…The abnormal protein metabolism has been observed in both obesity and ALS [ 165 ]. Some studies found that GGNBP2 is associated with BMI and waist-hip ratio [ 166 ]. GGNBP2 is also a tumour suppressor involved in several kinds of cancers [ 167 ].…”

Section: Discussionmentioning

confidence: 99%

Amyotrophic Lateral Sclerosis: A Diet Review

D’Antona

Caramenti

Porro

et al. 2021

Foods

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Amyotrophic lateral sclerosis (ALS) is a fatal disease related to upper and lower motor neurons degeneration. Although the environmental and genetic causes of this disease are still unclear, some factors involved in ALS onset such as oxidative stress may be influenced by diet. A higher risk of ALS has been correlated with a high fat and glutamate intake and β-methylamino-L-alanine. On the contrary, a diet based on antioxidant and anti-inflammatory compounds, such as curcumin, creatine, coenzyme Q10, vitamin E, vitamin A, vitamin C, and phytochemicals could reduce the risk of ALS. However, data are controversial as there is a discrepancy among different studies due to a limited number of samples and the many variables that are involved. In addition, an improper diet could lead to an altered microbiota and consequently to an altered metabolism that could predispose to the ALS onset. In this review we summarized some research that involve aspects related to ALS such as the epidemiology, the diet, the eating behaviour, the microbiota, and the metabolic diseases. Further research is needed to better comprehend the role of diet and the metabolic diseases in the mechanisms leading to ALS onset and progression.

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Shared Genetic Links Between Amyotrophic Lateral Sclerosis and Obesity-Related Traits: A Genome-Wide Association Study

Cited by 5 publications

References 4 publications

Body mass index associates with amyotrophic lateral sclerosis survival and metabolomic profiles

Body mass index associates with amyotrophic lateral sclerosis survival and metabolomic profiles

Investigating shared genetic architecture between obesity and multiple sclerosis

Amyotrophic Lateral Sclerosis: A Diet Review

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