Genetic Stratification of Age-Dependent Parkinson's Disease Risk by Polygenic Hazard Score.
Genetic Stratification of Age-Dependent Parkinson's Disease Risk by Polygenic Hazard Score.
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DOI：
10.1002/mds.28808
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发表时间：
2022-01
影响因子：
8.6
通讯作者：
Andreassen, Ole A.
中科院分区：
文献类型：
--
作者：
Pihlstrom, Lasse;Fan, Chun C.;Frei, Oleksandr;Tan, Manuela;Karunamuni, Roshan A.;Blauwendraat, Cornelis;Bandres-Ciga, Sara;Gan-Or, Ziv;Grosset, Donald G.;Dale, Anders M.;Seibert, Tyler M.;Andreassen, Ole A.
多基因危险评分捕捉常见遗传变异对帕金森病年龄依赖性风险的影响，并可能在临床上用于个体风险分层。建立并验证散发性帕金森病多基因危险评分模型。基于考克斯回归框架的遗传关联研究中多基因风险评分模型的训练和独立验证。全基因组关联研究多中心数据集的生物信息学分析。一个包含11,693名帕金森病患者和9,841名对照的参考数据集，一个包含5112名PD患者和5372名对照的大型测试数据集，以及一个包含360名患者和160名对照的小型单一研究验证样本。常见的单核苷酸多态性以前与帕金森病相关。患者帕金森病发作时的年龄或对照组末次健康检查时的年龄。多基因风险评分可预测帕金森病的发病当比较最高与最低风险十分位数时，风险比为3.78（95% CI 3.49-4.10）。该评分与发病率的流行病学数据相结合，以估计各年龄组的遗传分层瞬时帕金森病风险。我们证明了多基因危害方法在帕金森病中的可行性，将遗传对疾病风险和发病年龄的影响整合到一个模型中。这种方法有望在未来的疾病修饰疗法的临床试验中进行风险分层，其目的是推迟帕金森病的发作。
A polygenic hazard score captures the influence of common genetic variation on age-dependent risk of Parkinson’s disease and could be clinically useful for individual risk stratification. To develop and validate a polygenic hazard score model in sporadic Parkinson’s disease. Training and independent validation of a polygenic hazard score model in a genetic association study based on a Cox regression framework. Bioinformatic analyses of multicenter datasets from genome-wide association studies. A reference dataset of 11,693 Parkinson’s disease patients and 9,841 controls, a large test dataset of 5112 PD patients and 5372 controls and a small single-study validation sample of 360 patients and 160 controls. Common single-nucleotide polymorphisms previously associated with Parkinson’s disease. Age at onset of Parkinson’s disease in patients or last healthy examination in controls. A polygenic hazard score predicts onset of Parkinson’s disease. The hazard ratio was 3.78 (95% CI 3.49–4.10) when comparing the highest to the lowest risk decile. The score is combined with epidemiological data on incidence rate to estimate genetically stratified instantaneous Parkinson’s disease risk across age groups. We demonstrate the feasibility of a polygenic hazard approach in Parkinson’s disease, integrating the genetic effects on disease risk and age at onset in a single model. The approach holds promise for risk stratification in future clinical trials of disease-modifying therapies, which aim to postpone the onset of Parkinson’s disease.
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全基因组生存研究确定了帕金森病认知进展的新突触位点和多基因评分
影响因子：
30.8
作者：
Liu G;Peng J;Liao Z;Locascio JJ;Corvol JC;Zhu F;Dong X;Maple-Grødem J;Campbell MC;Elbaz A;Lesage S;Brice A;Mangone G;Growdon JH;Hung AY;Schwarzschild MA;Hayes MT;Wills AM;Herrington TM;Ravina B;Shoulson I;Taba P;Kõks S;Beach TG;Cormier-Dequaire F;Alves G;Tysnes OB;Perlmutter JS;Heutink P;Amr SS;van Hilten JJ;Kasten M;Mollenhauer B;Trenkwalder C;Klein C;Barker RA;Williams-Gray CH;Marinus J;International Genetics of Parkinson Disease Progression (IGPP) Consortium;Scherzer CR
通讯作者：
Scherzer CR
影响因子：
4.8
作者：
Karunamuni RA;Huynh-Le MP;Fan CC;Thompson W;Eeles RA;Kote-Jarai Z;Muir K;Lophatananon A;UKGPCS collaborators;Schleutker J;Pashayan N;Batra J;APCB BioResource (Australian Prostate Cancer BioResource);Grönberg H;Walsh EI;Turner EL;Lane A;Martin RM;Neal DE;Donovan JL;Hamdy FC;Nordestgaard BG;Tangen CM;MacInnis RJ;Wolk A;Albanes D;Haiman CA;Travis RC;Stanford JL;Mucci LA;West CML;Nielsen SF;Kibel AS;Wiklund F;Cussenot O;Berndt SI;Koutros S;Sørensen KD;Cybulski C;Grindedal EM;Park JY;Ingles SA;Maier C;Hamilton RJ;Rosenstein BS;Vega A;IMPACT Study Steering Committee and Collaborators;Kogevinas M;Penney KL;Teixeira MR;Brenner H;John EM;Kaneva R;Logothetis CJ;Neuhausen SL;Razack A;Newcomb LF;Canary PASS Investigators;Gamulin M;Usmani N;Claessens F;Gago-Dominguez M;Townsend PA;Roobol MJ;Zheng W;Profile Study Steering Committee;Mills IG;Andreassen OA;Dale AM;Seibert TM;PRACTICAL Consortium
通讯作者：
PRACTICAL Consortium
影响因子：
6.7
作者：
Duncan, Gordon William;Khoo, Tien Kheng;Burn, David J.
通讯作者：
Burn, David J.
影响因子：
8.6
作者：
Nalls, Mike A.;Escott-Price, Valentina;Williams, Nigel M.;Lubbe, Steven;Keller, Margaux F.;Morris, Huw R.;Singleton, Andrew B.
通讯作者：
Singleton, Andrew B.
DOI：
10.1038/s41431-020-0664-2
发表时间：
2020-10
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Karunamuni RA;Huynh-Le MP;Fan CC;Eeles RA;Easton DF;Kote-Jarai Z;Amin Al Olama A;Benlloch Garcia S;Muir K;Gronberg H;Wiklund F;Aly M;Schleutker J;Sipeky C;Tammela TLJ;Nordestgaard BG;Key TJ;Travis RC;Neal DE;Donovan JL;Hamdy FC;Pharoah P;Pashayan N;Khaw KT;Thibodeau SN;McDonnell SK;Schaid DJ;Maier C;Vogel W;Luedeke M;Herkommer K;Kibel AS;Cybulski C;Wokolorczyk D;Kluzniak W;Cannon-Albright L;Brenner H;Schöttker B;Holleczek B;Park JY;Sellers TA;Lin HY;Slavov C;Kaneva R;Mitev V;Batra J;Clements JA;Spurdle A;Australian Prostate Cancer BioResource (APCB);Teixeira MR;Paulo P;Maia S;Pandha H;Michael A;Mills IG;Andreassen OA;Dale AM;Seibert TM;PRACTICAL Consortium
通讯作者：
PRACTICAL Consortium