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Analysis of pleiotropic genetic effects on cognitive impairment, systemic inflammation, and plasma lipids in the Health and Retirement Study.

Publication ,  Journal Article
Lutz, MW; Casanova, R; Saldana, S; Kuchibhatla, M; Plassman, BL; Hayden, KM
Published in: Neurobiol Aging
August 2019

Variants associated with modulation of c-reactive protein (CRP) and plasma lipids have been investigated for polygenic overlap with Alzheimer's disease risk variants. We examined pleiotropic genetic effects on cognitive impairment conditioned on genetic variants (SNPs) associated with systemic inflammation as measured by CRP and with plasma lipids using data from the Health and Retirement Study. SNP enrichment was observed for cognitive impairment conditioned on the secondary phenotypes of plasma CRP and lipids. Fold enrichment of 100%-800% was observed for increasingly stringent p-value thresholds for SNPs associated with cognitive impairment conditional on plasma CRP, 80%-800% for low-density lipoprotein, and 80%-600% for total cholesterol. Significant associations (false discovery rate Q ≤ 0.05) between cognitive impairment, conditional with either CRP, low-density lipoprotein, or total cholesterol, were found for the locus on chromosome 19 that contains the APOE, TOMM40, APOC1, and PVRL2 genes. Relative numbers of significant SNPs in each of the genes differed by the conditional associations with the secondary phenotypes. Biological interpretation of both the genetic pleiotropy results and the individual genome-wide association results showed that the variants and proximal genes identified are involved in multiple pathological processes including cholesterol metabolism, inflammation, and mitochondrial transport. These findings are potentially important for Alzheimer's disease risk prediction and development of novel therapeutic approaches.

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Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

August 2019

Volume

80

Start / End Page

173 / 186

Location

United States

Related Subject Headings

  • Risk
  • Neurology & Neurosurgery
  • Nectins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Membrane Transport Proteins
  • Lipoproteins, LDL
  • Lipids
  • Inflammation
  • Humans
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
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Lutz, M. W., Casanova, R., Saldana, S., Kuchibhatla, M., Plassman, B. L., & Hayden, K. M. (2019). Analysis of pleiotropic genetic effects on cognitive impairment, systemic inflammation, and plasma lipids in the Health and Retirement Study. Neurobiol Aging, 80, 173–186. https://doi.org/10.1016/j.neurobiolaging.2018.10.028
Lutz, Michael W., Ramon Casanova, Santiago Saldana, Maragatha Kuchibhatla, Brenda L. Plassman, and Kathleen M. Hayden. “Analysis of pleiotropic genetic effects on cognitive impairment, systemic inflammation, and plasma lipids in the Health and Retirement Study.Neurobiol Aging 80 (August 2019): 173–86. https://doi.org/10.1016/j.neurobiolaging.2018.10.028.
Lutz MW, Casanova R, Saldana S, Kuchibhatla M, Plassman BL, Hayden KM. Analysis of pleiotropic genetic effects on cognitive impairment, systemic inflammation, and plasma lipids in the Health and Retirement Study. Neurobiol Aging. 2019 Aug;80:173–86.
Lutz, Michael W., et al. “Analysis of pleiotropic genetic effects on cognitive impairment, systemic inflammation, and plasma lipids in the Health and Retirement Study.Neurobiol Aging, vol. 80, Aug. 2019, pp. 173–86. Pubmed, doi:10.1016/j.neurobiolaging.2018.10.028.
Lutz MW, Casanova R, Saldana S, Kuchibhatla M, Plassman BL, Hayden KM. Analysis of pleiotropic genetic effects on cognitive impairment, systemic inflammation, and plasma lipids in the Health and Retirement Study. Neurobiol Aging. 2019 Aug;80:173–186.
Journal cover image

Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

August 2019

Volume

80

Start / End Page

173 / 186

Location

United States

Related Subject Headings

  • Risk
  • Neurology & Neurosurgery
  • Nectins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Membrane Transport Proteins
  • Lipoproteins, LDL
  • Lipids
  • Inflammation
  • Humans
  • Genome-Wide Association Study