Plasma Concentrations of Calcium and Risk of Alzheimer Disease—Observational and Genetic Studies
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Plasma Concentrations of Calcium and Risk of Alzheimer Disease—Observational and Genetic Studies. / Thomassen, Jesper Qvist; Nordestgaard, Børge G.; Tybjærg-Hansen, Anne; Frikke-Schmidt, Ruth.
In: Clinical Chemistry, Vol. 69, No. 5, 2023, p. 525-536.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Plasma Concentrations of Calcium and Risk of Alzheimer Disease—Observational and Genetic Studies
AU - Thomassen, Jesper Qvist
AU - Nordestgaard, Børge G.
AU - Tybjærg-Hansen, Anne
AU - Frikke-Schmidt, Ruth
N1 - Publisher Copyright: © American Association for Clinical Chemistry 2023. All rights reserved.
PY - 2023
Y1 - 2023
N2 - BACKGROUND: Dysregulation of calcium ion homeostasis in neurons is well documented in Alzheimer disease (AD), and high plasma calcium concentrations have been associated with cognitive decline in the elderly; however, a potential causal nature for this association has not been elucidated. METHODS: Plasma calcium ion concentrations of 97 968 individuals from the Copenhagen General Population Study (CGPS) were included and multifac-torial Cox regressions using splines or quartiles was performed to investigate the observational association. A plasma calcium ion genome-wide association study (GWAS) was performed in 2 independent subgroups of the CGPS. The plasma calcium ion GWAS and publicly available genomic data sets for plasma total calcium and AD were used to perform the currently most powerful 2-sample Mendelian randomization studies. RESULTS: The hazard ratio for lowest vs highest quartile of the calcium ion concentration was 1.24 (95% CI, 1.08–1.43) for AD. The plasma calcium ion GWAS identified 3 independent loci. None of the genetic instruments for plasma concentrations of calcium ions or total calcium were associated with AD risk. CONCLUSIONS: High plasma concentrations of calcium ions were observationally associated with increased risk of AD but genetic associations were not found, suggesting that the observational findings may be due to reverse causation or residual confounding.
AB - BACKGROUND: Dysregulation of calcium ion homeostasis in neurons is well documented in Alzheimer disease (AD), and high plasma calcium concentrations have been associated with cognitive decline in the elderly; however, a potential causal nature for this association has not been elucidated. METHODS: Plasma calcium ion concentrations of 97 968 individuals from the Copenhagen General Population Study (CGPS) were included and multifac-torial Cox regressions using splines or quartiles was performed to investigate the observational association. A plasma calcium ion genome-wide association study (GWAS) was performed in 2 independent subgroups of the CGPS. The plasma calcium ion GWAS and publicly available genomic data sets for plasma total calcium and AD were used to perform the currently most powerful 2-sample Mendelian randomization studies. RESULTS: The hazard ratio for lowest vs highest quartile of the calcium ion concentration was 1.24 (95% CI, 1.08–1.43) for AD. The plasma calcium ion GWAS identified 3 independent loci. None of the genetic instruments for plasma concentrations of calcium ions or total calcium were associated with AD risk. CONCLUSIONS: High plasma concentrations of calcium ions were observationally associated with increased risk of AD but genetic associations were not found, suggesting that the observational findings may be due to reverse causation or residual confounding.
U2 - 10.1093/clinchem/hvad030
DO - 10.1093/clinchem/hvad030
M3 - Journal article
C2 - 36950916
AN - SCOPUS:85181806639
VL - 69
SP - 525
EP - 536
JO - Clinical Chemistry
JF - Clinical Chemistry
SN - 0009-9147
IS - 5
ER -
ID: 386611442