Work

Unveiling the Genetic Association Between Hemoglobin Concentration and Amyotrophic Lateral Sclerosis

Year: 2025

Type: article

Abstract: ABSTRACT Background Although previous studies have suggested an association between hemoglobin (Hb) concentration and amyotrophic lateral sclerosis (ALS), the precise cause‐and‐effect relationship between them is still unclear. This study aims to investigate the causal correlation between Hb concentration and ALS, and explore the potential genes related to their association. Methods We extracted summary statistical data of Hb concentration and ALS from genome‐wide association studies (GWAS), performed Mendelian randomization (MR) analyses, and conducted RNA sequencing of motor neurons different from ALS patient‐derived induced pluripotent stem cells (iPSCs), followed by an intersection analysis between differentially expressed genes (DEGs) in ALS motor neurons and selected instrumental variables (IVs) associated with Hb concentration. Results As a result, Hb concentration had a negative causal relationship with the risk of ALS, established through IVW (OR = 0.854; 95% CI: 0.767–0.951; p = 0.00418) of the univariable MR analysis. A multivariable MR further confirmed that this causal link remained robust, even when accounting for confounders including systolic blood pressure, total cholesterol levels, body mass index, LDL cholesterol, diastolic blood pressure, and smoking. Importantly, genetically predicted ALS did not show a causal connection to Hb concentration. Additionally, RNA sequencing analysis and qRT‐PCR results revealed that transcripts for BACH1 and FLVCR1 were upregulated, while those for TRIM58 were downregulated in SOD1 D90A ALS motor neurons, compared to the control. In motor neurons differentiated from a sporadic ALS patient‐derived iPSCs, qRT‐PCR showed increased transcript levels of BACH1 , and decreased transcript levels of FLVCR1 and TRIM58 . These three genes were intersected with harmonized SNPs between Hb concentration and ALS. Conclusion Our study concludes that genetically predicted Hb concentration exhibited an independent inverse causal association with the risk of developing ALS, with potential involvement of genes such as BACH1 , FLVCR1 , and TRIM58 .

Source: Brain and Behavior

DOI: 10.1002/brb3.71152

Authors: Hongmei Luo, Yujie Yang, Xiaojian Cao, Chunchu Deng, Hong Chen

Institutions: Tongji Hospital, Huazhong University of Science and Technology

Language: English

Topic: Amyotrophic Lateral Sclerosis Research

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,630