4.6 Article

Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment

期刊

TRANSLATIONAL NEURODEGENERATION
卷 10, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s40035-021-00259-w

关键词

Polygenic risk score; Mild cognitive impairment; Alzheimer's disease; Disease progression; APOE epsilon 4

资金

  1. Alzheimer's Disease Neuroimaging Initiative (National Institutes of Health) [U01 AG024904]
  2. DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
  3. National Institute on Aging
  4. National Institute of Biomedical Imaging and Bioengineering
  5. Alzheimer's Association
  6. Alzheimer's Drug Discovery Foundation
  7. Araclon Biotech
  8. Biogen
  9. Bristol-Myers Squibb Company
  10. CereSpir, Inc.
  11. Cogstate
  12. Elan Pharmaceuticals, Inc.
  13. Eli Lilly and Company
  14. EuroImmun
  15. F. Hoffmann-La Roche Ltd
  16. Fujirebio
  17. Johnson & Johnson Pharmaceutical Research & Development LLC.
  18. Merck Co., Inc.
  19. Meso Scale Diagnostics, LLC.
  20. NeuroRx Research
  21. Novartis Pharmaceuticals Corporation
  22. Pfizer Inc.
  23. Piramal Imaging
  24. Takeda Pharmaceutical Company
  25. Canadian Institutes of Health Research
  26. ADNI clinical sites in Canada
  27. Foundation for the National Institutes of Health
  28. Northern California Institute for Research and Education
  29. Laboratory for Neuro Imaging at the University of Southern California
  30. Servier
  31. Transition Therapeutics
  32. Neurotrack Technologies
  33. AbbVie
  34. BioClinica, Inc.
  35. Eisai Inc.
  36. GE Healthcare
  37. IXICO Ltd.
  38. Lumosity
  39. Lundbeck
  40. Janssen Alzheimer Immunotherapy Research & Development, LLC.

向作者/读者索取更多资源

The study found that polygenic risk scores (PRS) could predict the risk of MCI patients progressing to dementia, with a stronger association in APOE epsilon 4 non-carriers.
Background: The combinatorial effect of multiple genetic factors calculated as a polygenic risk score (PRS) has been studied to predict disease progression to Alzheimer's disease (AD) from mild cognitive impairment (MCI). Previous studies have investigated the performance of PRS in the prediction of disease progression to AD by including and excluding single nucleotide polymorphisms within the region surrounding the APOE gene. These studies may have missed the APOE genotype-specific predictability of PRS for disease progression to AD. Methods: We analyzed 732 MCI from the Alzheimer's Disease Neuroimaging Initiative cohort, including those who progressed to AD within 5 years post-baseline (n = 270) and remained stable as MCI (n = 462). The predictability of PRS including and excluding the APOE region (PRS+APOE and PRS-APOE) on the conversion to AD and its interaction with the APOE epsilon 4 carrier status were assessed using Cox regression analyses. Results: PRS+APOE (hazard ratio [HR] 1.468, 95% CI 1.335-1.615) and PRS-APOE (HR 1.293, 95% CI 1.157-1.445) were both associated with a significantly increased risk of MCI progression to dementia. The interaction between PRS+APOE and APOE epsilon 4 carrier status was significant with a P-value of 0.0378. The association of PRSs with the progression risk was stronger in APOE epsilon 4 non-carriers (PRS+APOE: HR 1.710, 95% CI 1.244-2.351; PRS-APOE: HR 1.429, 95% CI 1.182-1.728) than in APOE epsilon 4 carriers (PRS+APOE: HR 1.167, 95% CI 1.005-1.355; PRS-APOE: HR 1.172, 95% CI 1.020-1.346). Conclusions: PRS could predict the conversion of MCI to dementia with a stronger association in APOE epsilon 4 non-carriers than APOE epsilon 4 carriers. This indicates PRS as a potential genetic predictor particularly for MCI with no APOE epsilon 4 alleles.

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