ALS-, metal-polygenic risk score does not alter significance of association with ALS risk, survival
FRIDAY, Aug. 9, 2024 (HealthDay News) — Elevated metal levels in plasma and urine are associated with amyotrophic lateral sclerosis (ALS) risk and survival, according to a study published online Aug. 6 in the Journal of Neurology, Neurosurgery & Psychiatry.
Dae-Gyu Jang, Ph.D., from the University of Michigan in Ann Arbor, and colleagues examined associations of metal measures in plasma and urine with ALS risk and survival. The association between exposure mixtures and ALS risk and survival and exposure source was examined using environmental risk scores (ERS). ALS- and metal-polygenic risk scores (PGS) were also constructed.
Plasma and urine samples were included for 454 ALS patients and 294 controls. The researchers observed significant associations for elevated levels of individuals metals, including copper, selenium, and zinc, with ALS risk and survival. ERS representing metal mixtures was strongly associated with ALS risk (odds ratios, 2.95 and 3.10 for plasma and urine, respectively) and with poorer ALS survival (hazard ratios, 1.37 and 1.44 for plasma and urine, respectively). The significance of the association of metals with ALS risk and survival was not altered by the addition of ALS-PGS or metal-PGS. Elevated ERS was seen in association with occupations with high potential metal exposure. Occupational and nonoccupational exposures to metals were associated with measured plasma and urine metal levels.
“We demonstrate that metal mixtures, as represented by cumulative ERS, associate with increased ALS risk and reduced ALS survival, regardless of genetic predisposition. These associations correlate with self-reported occupational metal exposure,” the authors write. “Overall, these results offer valuable insights into the complexities of ALS pathogenesis.”
Two authors are listed as inventors on a patent titled “Methods for Treating Amyotrophic Lateral Sclerosis” that targets immune pathways for use in ALS therapeutics; one author disclosed ties to Evidera.
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