Multiple Metal Exposures Associate With Higher Amyotrophic Lateral Sclerosis Risk and Mortality Independent of Genetic Risk and Correlate to Self-reported Exposures: a Case-control Study.

Details

• Alternative Title:
  Journal of Neurology, Neurosurgery, and Psychiatry, 2025, v. 96, no. 4: Multiple Metal Exposures Associate With Higher Amyotrophic Lateral Sclerosis Risk and Mortality Independent of Genetic Risk and Correlate to Self-reported Exposures: a Case-control Study.
• Journal Article:
  Journal of Neurology, Neurosurgery, and Psychiatry
• Personal Author:
  Jang, Dae Gyu ; Dou, John ; Koubek, Emily J. ; Teener, Samuel ; Zhao, Lili ; Bakulski, Kelly M. ; Mukherjee, Bhramar ; Batterman, Stuart A. ; Feldman, Eva L. ; Goutman, Stephen A.
• Description:
  The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival and exposure sources.
  
  Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry. ORs and HRs for each metal were computed using risk and survival models. Environmental risk scores (ERS) were created to evaluate the association between exposure mixtures and ALS risk and survival and exposure source. ALS (ALS-PGS) and metal (metal-PGS) polygenic risk scores were constructed from an independent genome-wide association study and relevant literature-selected single-nucleotide polymorphisms.
  
  Plasma and urine samples from 454 ALS and 294 control participants were analysed. Elevated levels of individual metals, including copper, selenium and zinc, significantly associated with ALS risk and survival. ERS representing metal mixtures strongly associated with ALS risk (plasma, OR=2.95, CI=2.38-3.62, p<0.001; urine, OR=3.10, CI=2.43-3.97, p<0.001) and poorer ALS survival (plasma, HR=1.37, CI=1.20-1.58, p<0.001; urine, HR=1.44, CI=1.23-1.67, p<0.001). Addition of the ALS-PGS or metal-PGS did not alter the significance of metals with ALS risk and survival. Occupations with high potential of metal exposure associated with elevated ERS. Additionally, occupational and non-occupational metal exposures were associated with measured plasma and urine metals.
  
  Metals in plasma and urine associated with increased ALS risk and reduced survival, independent of genetic risk, and correlated with occupational and non-occupational metal exposures. These data underscore the significance of metal exposure in ALS risk and progression.
• Content Notes:
  Author manuscript
• Subjects:
  • Humans
  • Amyotrophic Lateral Sclerosis
  • Male
  • Female
  • Middle Aged
  • Case-Control Studies
  • Aged
  • Metals
  • Environmental Exposure
  • Copper
  More +
• Keywords:
  • Amyotrophic lateral sclerosis (ALS)
  • metals
  • polygenic risk score
  • environmental risk score
• Source:
  Journal of Neurology, Neurosurgery, and Psychiatry, 2025, v. 96, no. 4
• DOI:
  https://doi.org/10.1136/jnnp-2024-333978
• ISSN:
  0022-3050 ; 1468-330X
• Pubmed ID:
  39107037
• Pubmed Central ID:
  PMC12841235
• Document Type:
  Text
• Funding:
  R01TS000344/ACL/ACL HHSUnited States/ ; R01 ES030049/ES/NIEHS NIH HHSUnited States/ ; P30 CA023108/CA/NCI NIH HHSUnited States/ ; K23 ES027221/ES/NIEHS NIH HHSUnited States/ ; R01 NS127188/NS/NINDS NIH HHSUnited States/ ; R01 TS000344/TS/ATSDR CDC HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  329-339 (29 pdf pages)
• Volume:
  96
• Issue:
  4
• Download URL:
  https://stacks.cdc.gov/view/cdc/262062/cdc_262062_DS1.pdf
• File Type:
  [PDF - 2.78 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:0227757854838f106597453ba2da0efbcf678e2ffa311cd0dfe8c0e6dc5e91427c1c4a7ab0b877a768d0030311ce4eef0eda15027aef40d015d84ce4bce53d5c