Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals

被引：7

作者：

Yu, Chenglong ^{[1
,19
]}

Ryan, Joanne ^{[1
]}

Orchard, Suzanne G. ^{[1
]}

Robb, Catherine ^{[1
]}

Woods, Robyn L. ^{[1
,13
]}

Wolfe, Rory ^{[1
]}

Renton, Alan E. ^{[2
,3
,4
]}

Goate, Alison M. ^{[2
,3
,4
]}

Brodtmann, Amy ^{[5
,6
]}

Shah, Raj C. ^{[7
,8
]}

Chong, Trevor T. -J. ^{[9
,10
,11
]}

Sheets, Kerry ^{[12
,13
]}

Kyndt, Christopher ^{[14
,15
]}

Sood, Ajay ^{[16
]}

Storey, Elsdon ^{[1
]}

Murray, Anne M. ^{[12
,13
,17
]}

McNeil, John J. ^{[1
]}

Lacaze, Paul ^{[1
,18
]}

机构：

[1] Monash Univ, Sch Publ Hlth & Prevent Med, Melbourne, Vic, Australia

[2] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA

[3] Ronald M Loeb Ctr Alzheimers Disease, Icahn Sch Med Mt Sinai, NewYork, New York, NY USA

[4] Icahn Sch Med Mt Sinai, Dept Neurol & Neurosci, New York, NY USA

[5] Monash Univ, Cent Clin Sch, Cognit Hlth Initiat, Melbourne, Vic, Australia

[6] Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia

[7] Dept Family & Prevent Med, Chicago, IL USA

[8] Rush Alzheimers Dis Ctr, Chicago, IL USA

[9] Monash Univ, Turner Inst Brain & Mental Hlth, Sch Psychol Sci, Clayton, Vic, Australia

[10] Alfred Hlth, Dept Neurol, Melbourne, Vic, Australia

[11] St Vincents Hosp, Dept Clin Neurosci, Melbourne, Vic, Australia

[12] Univ Minnesota, Dept Med, Minneapolis, MN USA

[13] Hennepin Healthcare, Div Geriatr, Minneapolis, MN USA

[14] Dept Neurol, Melbourne Hlth, Parkville, Vic, Australia

[15] Eastern Hlth, Dept Neurosci, Box Hill, Vic, Australia

[16] Rush Univ, Med Ctr, Dept Neurol, Chicago, IL USA

[17] Hennepin Healthcare Res Inst, Berman Ctr Outcomes & Clin Res, Hennepin Healthcare, Minneapolis, MN USA

[18] Univ Minnesota, Minneapolis, MN USA

[19] Monash Univ, Sch Publ Hlth & Prevent Med, Level5, 553St Kilda Rd, Melbourne, Vic 3004, Australia

来源：

ALZHEIMERS & DEMENTIA | 2023年 / 19卷 / 12期

基金：

英国医学研究理事会; 美国国家卫生研究院; 芬兰科学院; 澳大利亚国家健康与医学研究理事会;

关键词：

APOE gene; incident dementia; longitudinal study; polygenic risk score; ALZHEIMERS-DISEASE; NORMATIVE DATA; LOCI; METAANALYSIS; ASSOCIATION; IMPAIRMENT; GENOTYPE; BETA; AGE;

D O I：

10.1002/alz.13113

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

IntroductionRecent genome-wide association studies identified new dementia-associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort. MethodsWe used Cox models and area under the curve (AUC) to validate new PRSs (PRS-83SNP, PRS-SBayesR, and PRS-CS) compared with an older PRS-23SNP in 12,031 initially-healthy participants >= 70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. ResultsPRS-83SNP, PRS-SBayesR, and PRS-CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [APOE] epsilon 4) hazard ratios per standard deviation (SD) of 1.35 (1.23-1.47), 1.37 (1.25-1.50), and 1.42 (1.30-1.56), respectively. The AUC of a model containing conventional/non-genetic factors and APOE was 74.7%. This was improved to 75.7% (p = 0.007), 76% (p = 0.004), and 76.1% (p = 0.003) with addition of PRS-83SNP, PRS-SBayesR, and PRS-CS, respectively. The PRS-23SNP did not improve AUC (74.7%, p = 0.95). ConclusionNew PRSs for dementia significantly improve risk-prediction performance, but still account for less risk than APOE genotype overall.

引用

页码：5333 / 5342

页数：10

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