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Predictability of polygenic risk score for progression to dementia and its interaction with APOEε4 in mild cognitive impairment

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Translational Neurodegeneration 2021年第3期10卷 412-420页

作者： jung‑min pyun Young Ho Park Keon‑Joo Lee SangYun Kim Andrew J.Saykin Kwangsik Nho Department of Neurology Uijeongbu Eulji Medical CenterEulji UniversityUijeongbuRepublic of Korea Department of Neurology Seoul National University Bundang Hospital and Seoul National University College of Medi‑cineSeongnamRepublic of Korea Department of Radiology and Imaging Sciences and the Indiana Alzheimer Disease CenterIndiana University School of MedicineIndianapolisINUSA Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisINUSA Center for Computational Biology and Bioinformatics Indiana University School of MedicineIndianapolisINUSA.

Background:The combinatorial efect 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 *** studies may have missed the APOE genotype-specifc predictability of PRS for disease progression to ***: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 APOEε4 carrier status were assessed using Cox regression ***: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 signifcantly increased risk of MCI progression to *** interaction between PRS_(+APOE) and APOEε4 carrier status was signifcant with a P-value of *** association of PRSs with the progression risk was stronger in APOEε4 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 APOEε4 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 APOEε4 noncarriers than APOEε4 *** indicates PRS as a potential genetic predictor particularly for MCI with no APOEε4 alleles.

关键词： Polygenic risk score Mild cognitive impairment Alzheimer’s disease Disease progression APOEε4

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