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Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment.
Transl Neurodegener. 2021 08 31; 10(1):32.TN

Abstract

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 ε4 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 ε4 carrier status was significant with a P-value of 0.0378. The association of PRSs with the progression risk was stronger in APOE ε4 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 ε4 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 ε4 non-carriers than APOE ε4 carriers. This indicates PRS as a potential genetic predictor particularly for MCI with no APOE ε4 alleles.

Links

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Authors+Show Affiliations

Pyun JM
Department of Neurology, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu, Republic of Korea.
Park YH
Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea. kumimesy@snubh.org.
Lee KJ
Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea.
Kim S
Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea.
Saykin AJ
Department of Radiology and Imaging Sciences, and the Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Nho K
Department of Radiology and Imaging Sciences, and the Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA. knho@iu.edu. Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA. knho@iu.edu.
Alzheimer’s Disease Neuroimaging Initiative
No affiliation info available

MeSH

AgedAlzheimer DiseaseApolipoprotein E4Cognitive DysfunctionCohort StudiesDisease ProgressionFemaleFollow-Up StudiesHumansMagnetic Resonance ImagingMaleMultifactorial InheritancePolymorphism, Single NucleotidePredictive Value of TestsRisk Factors

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

34465370

Citation

Pyun, Jung-Min, et al. "Predictability of Polygenic Risk Score for Progression to Dementia and Its Interaction With APOE Ε4 in Mild Cognitive Impairment." Translational Neurodegeneration, vol. 10, no. 1, 2021, p. 32.
Pyun JM, Park YH, Lee KJ, et al. Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment. Transl Neurodegener. 2021;10(1):32.
Pyun, J. M., Park, Y. H., Lee, K. J., Kim, S., Saykin, A. J., & Nho, K. (2021). Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment. Translational Neurodegeneration, 10(1), 32. https://doi.org/10.1186/s40035-021-00259-w
Pyun JM, et al. Predictability of Polygenic Risk Score for Progression to Dementia and Its Interaction With APOE Ε4 in Mild Cognitive Impairment. Transl Neurodegener. 2021 08 31;10(1):32. PubMed PMID: 34465370.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment. AU - Pyun,Jung-Min, AU - Park,Young Ho, AU - Lee,Keon-Joo, AU - Kim,SangYun, AU - Saykin,Andrew J, AU - Nho,Kwangsik, AU - ,, Y1 - 2021/08/31/ PY - 2021/04/26/received PY - 2021/08/14/accepted PY - 2021/9/1/entrez PY - 2021/9/2/pubmed PY - 2022/1/29/medline KW - APOE ε4 KW - Alzheimer’s disease KW - Disease progression KW - Mild cognitive impairment KW - Polygenic risk score SP - 32 EP - 32 JF - Translational neurodegeneration JO - Transl Neurodegener VL - 10 IS - 1 N2 - 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 ε4 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 ε4 carrier status was significant with a P-value of 0.0378. The association of PRSs with the progression risk was stronger in APOE ε4 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 ε4 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 ε4 non-carriers than APOE ε4 carriers. This indicates PRS as a potential genetic predictor particularly for MCI with no APOE ε4 alleles. SN - 2047-9158 UR - https://www.unboundmedicine.com/medline/citation/34465370/Predictability_of_polygenic_risk_score_for_progression_to_dementia_and_its_interaction_with_APOE_ε4_in_mild_cognitive_impairment_ DB - PRIME DP - Unbound Medicine ER -