GenoRisk: A polygenic risk score for Alzheimer's disease.
GenoRisk: A polygenic risk score for Alzheimer's disease.
复制标题
DOI：
10.1002/trc2.12211
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
NIAGADS
中科院分区：
文献类型：
--
作者：
Dickson SP;Hendrix SB;Brown BL;Ridge PG;Nicodemus-Johnson J;Hardy ML;McKeany AM;Booth SB;Fortna RR;Kauwe JSK;NIAGADS
最近的临床试验正在考虑纳入不仅仅是载脂蛋白E(ApoE)ε4基因型，作为在结果分析中减少变异性的一种方式。病例对照数据被用来比较年龄、性别和58个阿尔茨海默病(AD)相关单核苷酸多态(SNPs)使用几个统计模型预测AD状态的能力。通过Brier评分和十次交叉验证来评估模型的性能。最佳模型中的基因型和性别×年龄估计与一般人群的年龄和截距估计相结合，形成个性化的遗传风险评分，称为年龄，并经性别调整的基因风险。包括年龄、年龄×性别交互作用、等位基因载脂蛋白E项和29个额外SNPs的弹性网络模型表现最好。该模型解释了与apoE基因相比，额外19%的遗传风险，并得到了0.747的曲线下面积。GenRisk可以改善对被确定进行预防研究的个人的风险评估。
Recent clinical trials are considering inclusion of more than just apolipoprotein E (APOE) ε4 genotype as a way of reducing variability in analysis of outcomes. Case‐control data were used to compare the capacity of age, sex, and 58 Alzheimer's disease (AD)–associated single nucleotide polymorphisms (SNPs) to predict AD status using several statistical models. Model performance was assessed with Brier scores and tenfold cross‐validation. Genotype and sex × age estimates from the best performing model were combined with age and intercept estimates from the general population to develop a personalized genetic risk score, termed age, and sex‐adjusted GenoRisk. The elastic net model that included age, age x sex interaction, allelic APOE terms, and 29 additional SNPs performed the best. This model explained an additional 19% of the heritable risk compared to APOE genotype alone and achieved an area under the curve of 0.747. GenoRisk could improve the risk assessment of individuals identified for prevention studies.
登录
查看更多内容
DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
4.2
作者：
Escott-Price, Valentina;Shoai, Maryam;Hardy, John
通讯作者：
Hardy, John
影响因子：
11.2
作者：
Pedersen, NL;Gatz, M;Johansson, B
通讯作者：
Johansson, B
影响因子：
3.5
作者：
Lee SH;Harold D;Nyholt DR;ANZGene Consortium;International Endogene Consortium;Genetic and Environmental Risk for Alzheimer's disease Consortium;Goddard ME;Zondervan KT;Williams J;Montgomery GW;Wray NR;Visscher PM
通讯作者：
Visscher PM