Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.
Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.
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DOI：
10.1038/s41588-019-0556-y
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发表时间：
2020-03
期刊：
影响因子：
30.8
通讯作者：
MacGregor S
中科院分区：
文献类型：
--
作者：
Craig JE;Han X;Qassim A;Hassall M;Cooke Bailey JN;Kinzy TG;Khawaja AP;An J;Marshall H;Gharahkhani P;Igo RP Jr;Graham SL;Healey PR;Ong JS;Zhou T;Siggs O;Law MH;Souzeau E;Ridge B;Hysi PG;Burdon KP;Mills RA;Landers J;Ruddle JB;Agar A;Galanopoulos A;White AJR;Willoughby CE;Andrew NH;Best S;Vincent AL;Goldberg I;Radford-Smith G;Martin NG;Montgomery GW;Vitart V;Hoehn R;Wojciechowski R;Jonas JB;Aung T;Pasquale LR;Cree AJ;Sivaprasad S;Vallabh NA;NEIGHBORHOOD consortium;UK Biobank Eye and Vision Consortium;Viswanathan AC;Pasutto F;Haines JL;Klaver CCW;van Duijn CM;Casson RJ;Foster PJ;Khaw PT;Hammond CJ;Mackey DA;Mitchell P;Lotery AJ;Wiggs JL;Hewitt AW;MacGregor S
青光眼是一种以视神经退行性变为特征的疾病，通过及时诊断和治疗可以预防。我们描述了67，040名英国生物银行参与者的视神经照片，并使用多性状遗传模型来识别青光眼的风险位点。一种新的青光眼多基因风险评分（PRS）使青光眼病例的有效风险分层成为可能，并改变了MYOC p.Gln368Ter（最常见的青光眼相关肌球蛋白变体）的突变率。在青光眼人群中，PRS最高十分位数的个体比最低十分位数的个体早10年达到青光眼的绝对风险，并且发展为晚期青光眼的风险增加15倍（最高10%与其余90% OR = 4.20）。在前瞻性监测的早期显性青光眼病例中，PRS可预测青光眼进展（P = 0.004），在晚期疾病中可预测手术干预（P = 3.6 × 10−6）。该青光眼PRS将有助于开发一种个性化的方法，用于早期治疗高风险个体，对低风险群体进行较低强度的监测和治疗。
Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterized optic nerve photographs of 67,040 UK Biobank participants and used a multitrait genetic model to identify risk loci for glaucoma. A novel glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases, and modifies penetrance of MYOC p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile, and are at 15-fold increased risk of developing advanced glaucoma (top 10% vs. remaining 90% OR = 4.20). The PRS predicts glaucoma progression in prospectively monitored early manifest glaucoma cases (P = 0.004), and surgical intervention in advanced disease (P = 3.6 × 10−6). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment possible for lower-risk groups.
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影响因子：
3.5
作者：
Gao, X. Raymond;Huang, Hua;Kim, Heejin
通讯作者：
Kim, Heejin
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
16.6
作者：
Choquet H;Paylakhi S;Kneeland SC;Thai KK;Hoffmann TJ;Yin J;Kvale MN;Banda Y;Tolman NG;Williams PA;Schaefer C;Melles RB;Risch N;John SWM;Nair KS;Jorgenson E
通讯作者：
Jorgenson E
DOI：
10.1093/jnci/djw302
发表时间：
2017-07-01
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Kuchenbaecker KB;McGuffog L;Barrowdale D;Lee A;Soucy P;Dennis J;Domchek SM;Robson M;Spurdle AB;Ramus SJ;Mavaddat N;Terry MB;Neuhausen SL;Schmutzler RK;Simard J;Pharoah PDP;Offit K;Couch FJ;Chenevix-Trench G;Easton DF;Antoniou AC
通讯作者：
Antoniou AC
DOI：
10.1200/jco.2016.69.4935
发表时间：
2017-07-10
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Lecarpentier J;Silvestri V;Kuchenbaecker KB;Barrowdale D;Dennis J;McGuffog L;Soucy P;Leslie G;Rizzolo P;Navazio AS;Valentini V;Zelli V;Lee A;Amin Al Olama A;Tyrer JP;Southey M;John EM;Conner TA;Goldgar DE;Buys SS;Janavicius R;Steele L;Ding YC;Neuhausen SL;Hansen TVO;Osorio A;Weitzel JN;Toss A;Medici V;Cortesi L;Zanna I;Palli D;Radice P;Manoukian S;Peissel B;Azzollini J;Viel A;Cini G;Damante G;Tommasi S;Peterlongo P;Fostira F;Hamann U;Evans DG;Henderson A;Brewer C;Eccles D;Cook J;Ong KR;Walker L;Side LE;Porteous ME;Davidson R;Hodgson S;Frost D;Adlard J;Izatt L;Eeles R;Ellis S;Tischkowitz M;EMBRACE;Godwin AK;Meindl A;Gehrig A;Dworniczak B;Sutter C;Engel C;Niederacher D;Steinemann D;Hahnen E;Hauke J;Rhiem K;Kast K;Arnold N;Ditsch N;Wang-Gohrke S;Wappenschmidt B;Wand D;Lasset C;Stoppa-Lyonnet D;Belotti M;Damiola F;Barjhoux L;Mazoyer S;GEMO Study Collaborators;Van Heetvelde M;Poppe B;De Leeneer K;Claes KBM;de la Hoya M;Garcia-Barberan V;Caldes T;Perez Segura P;Kiiski JI;Aittomäki K;Khan S;Nevanlinna H;van Asperen CJ;HEBON;Vaszko T;Kasler M;Olah E;Balmaña J;Gutiérrez-Enríquez S;Diez O;Teulé A;Izquierdo A;Darder E;Brunet J;Del Valle J;Feliubadalo L;Pujana MA;Lazaro C;Arason A;Agnarsson BA;Johannsson OT;Barkardottir RB;Alducci E;Tognazzo S;Montagna M;Teixeira MR;Pinto P;Spurdle AB;Holland H;KConFab Investigators;Lee JW;Lee MH;Lee J;Kim SW;Kang E;Kim Z;Sharma P;Rebbeck TR;Vijai J;Robson M;Lincoln A;Musinsky J;Gaddam P;Tan YY;Berger A;Singer CF;Loud JT;Greene MH;Mulligan AM;Glendon G;Andrulis IL;Toland AE;Senter L;Bojesen A;Nielsen HR;Skytte AB;Sunde L;Jensen UB;Pedersen IS;Krogh L;Kruse TA;Caligo MA;Yoon SY;Teo SH;von Wachenfeldt A;Huo D;Nielsen SM;Olopade OI;Nathanson KL;Domchek SM;Lorenchick C;Jankowitz RC;Campbell I;James P;Mitchell G;Orr N;Park SK;Thomassen M;Offit K;Couch FJ;Simard J;Easton DF;Chenevix-Trench G;Schmutzler RK;Antoniou AC;Ottini L
通讯作者：
Ottini L