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This study aims to investigate the causal correlation between Hb concentration and ALS, and explore the potential genes related to their association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We extracted summary statistical data of Hb concentration and ALS from genome\u2010wide association studies (GWAS), performed Mendelian randomization (MR) analyses, and conducted RNA sequencing of motor neurons different from ALS patient\u2010derived 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u20130.951;\n                      <jats:italic>p<\/jats:italic>\n                      = 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\u2010PCR results revealed that transcripts for\n                      <jats:italic>BACH1<\/jats:italic>\n                      and\n                      <jats:italic>FLVCR1<\/jats:italic>\n                      were upregulated, while those for\n                      <jats:italic>TRIM58<\/jats:italic>\n                      were downregulated in\n                      <jats:italic>SOD1<\/jats:italic>\n                      <jats:sup>D90A<\/jats:sup>\n                      ALS motor neurons, compared to the control. In motor neurons differentiated from a sporadic ALS patient\u2010derived iPSCs, qRT\u2010PCR showed increased transcript levels of\n                      <jats:italic>BACH1<\/jats:italic>\n                      , and decreased transcript levels of\n                      <jats:italic>FLVCR1<\/jats:italic>\n                      and\n                      <jats:italic>TRIM58<\/jats:italic>\n                      . These three genes were intersected with harmonized SNPs between Hb concentration and ALS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>BACH1<\/jats:italic>\n                      ,\n                      <jats:italic>FLVCR1<\/jats:italic>\n                      , and\n                      <jats:italic>TRIM58<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  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