Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.
Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.
复制标题
DOI：
10.1038/s41588-023-01584-8
复制
发表时间：
2024-01
期刊：
影响因子：
30.8
通讯作者：
Mata, Ignacio
中科院分区：
文献类型：
--
作者：
Kim, Jonggeol Jeffrey;Vitale, Dan;Otani, Diego Veliz;Lian, Michelle Mulan;Heilbron, Karl;Aslibekyan, Stella;Auton, Adam;Babalola, Elizabeth;Bell, Robert K.;Bielenberg, Jessica;Bryc, Katarzyna;Bullis, Emily;Cannon, Paul;Coker, Daniella;Partida, Gabriel Cuellar;Dhamija, Devika;Das, Sayantan;Elson, Sarah L.;Eriksson, Nicholas;Filshtein, Teresa;Fitch, Alison;Fletez-Brant, Kipper;Fontanillas, Pierre;Freyman, Will;Granka, Julie M.;Hernandez, Alejandro;Hicks, Barry;Hinds, David A.;Jewett, Ethan M.;Jiang, Yunxuan;Kukar, Katelyn;Kwong, Alan;Lin, Keng-Han;Llamas, Bianca A.;Lowe, Maya;McCreight, Jey C.;McIntyre, Matthew H.;Micheletti, Steven J.;Moreno, Meghan E.;Nandakumar, Priyanka;Nguyen, Dominique T.;Noblin, Elizabeth S.;O'Connell, Jared;Petrakovitz, Aaron A.;Poznik, G. David;Reynoso, Alexandra;Schloetter, Madeleine;Schumacher, Morgan;Shastri, Anjali J.;Shelton, Janie F.;Shi, Jingchunzi;Shringarpure, Suyash;Su, Qiaojuan Jane;Tat, Susana A.;Tchakoute, Christophe Toukam;Tran, Vinh;Tung, Joyce Y.;Wang, Xin;Wang, Wei;Weldon, Catherine H.;Wilton, Peter;Wong, Corinna D.;Iwaki, Hirotaka;Lake, Julie;Solsberg, Caroline Warly;Leonard, Hampton;Makarious, Mary B.;Tan, Eng-King;Singleton, Andrew B.;Bandres-Ciga, Sara;Noyce, Alastair J.;Gatto, Emilia M.;Kauffman, Marcelo;Khachatryan, Samson;Tavadyan, Zaruhi;Shepherd, Claire E.;Hunter, Julie;Kumar, Kishore;Ellis, Melina;Renteria, Miguel E.;Koks, Sulev;Zimprich, Alexander;Schumacher-Schuh, Artur F.;Rieder, Carlos;Awad, Paula Saffie;Tumas, Vitor;Camargos, Sarah;Fon, Edward A.;Monchi, Oury;Fon, Ted;Galleguillos, Benjamin Pizarro;Miranda, Marcelo;Bustamante, Maria Leonor;Olguin, Patricio;Chana, Pedro;Tang, Beisha;Shang, Huifang;Guo, Jifeng;Chan, Piu;Luo, Wei;Arboleda, Gonzalo;Orozc, Jorge;del Rio, Marlene Jimenez;Hernandez, Alvaro;Salama, Mohamed;Kamel, Walaa A.;Zewde, Yared Z.;Brice, Alexis;Corvol, Jean-Christophe;Westenberger, Ana;Illarionova, Anastasia;Mollenhauer, Brit;Klein, Christine;Vollstedt, Eva-Juliane;Hopfner, Franziska;Hoglinger, Gunter;Madoev, Harutyun;Trinh, Joanne;Junker, Johanna;Lohmann, Katja;Lange, Lara M.;Sharma, Manu;Groppa, Sergiu;Gasser, Thomas;Fang, Zih-Hua;Akpalu, Albert;Xiromerisiou, Georgia;Hadjigorgiou, Georgios;Dagklis, Ioannis;Tarnanas, Ioannis;Stefanis, Leonidas;Stamelou, Maria;Dadiotis, Efthymios;Medina, Alex;Chan, Germaine Hiu-Fai;Ip, Nancy;Cheung, Nelson Yuk-Fai;Chan, Phillip;Zhou, Xiaopu;Kishore, Asha;Divya, K. P.;Pal, Pramod;Kukkle, Prashanth Lingappa;Rajan, Roopa;Borgohain, Rupam;Salari, Mehri;Quattrone, Andrea;Valente, Enza Maria;Parnetti, Lucilla;Avenali, Micol;Schirinzi, Tommaso;Funayama, Manabu;Hattori, Nobutaka;Shiraishi, Tomotaka;Karimova, Altynay;Kaishibayeva, Gulnaz;Shambetova, Cholpon;Krueger, Rejko;Tan, Ai Huey;Ahmad-Annuar, Azlina;Norlinah, Mohamed Ibrahim;Murad, Nor Azian Abdul;Azmin, Shahrul;Lim, Shen-Yang;Mohamed, Wael;Tay, Yi Wen;Martinez-Ramirez, Daniel;Rodriguez-Violante, Mayela;Reyes-Perez, Paula;Tserensodnom, Bayasgalan;Ojha, Rajeev;Anderson, Tim J.;Pitcher, Toni L.;Sanyaolu, Arinola;Okubadejo, Njideka;Ojo, Oluwadamilola;Aasly, Jan O.;Pihlstrom, Lasse;Tan, Manuela;Ur-Rehman, Shoaib;Veliz-Otani, Diego;Cornejo-Olivas, Mario;Doquenia, Maria Leila;Rosales, Raymond;Vinuela, Angel;Iakovenko, Elena;Al Mubarak, Bashayer;Umair, Muhammad;Amod, Ferzana;Carr, Jonathan;Bardien, Soraya;Jeon, Beomseok;Kim, Yun Joong;Cubo, Esther;Alvarez, Ignacio;Hoenicka, Janet;Beyer, Katrin;Perinan, Maria Teresa;Pastor, Pau;El-Sadig, Sarah;Brolin, Kajsa;Zweier, Christiane;Tinkhauser, Gerd;Krack, Paul;Lin, Chin-Hsien;Wu, Hsiu-Chuan;Kung, Pin-Jui;Wu, Ruey-Meei;Wu, Yihru;Amouri, Rim;Ben Sassi, Samia;Basak, A. Nazl;Genc, Gencer;Cakmak, Ozguer Oztop;Ertan, Sibel;Martinez-Carrasco, Alejandro;Schrag, Anette;Schapira, Anthony;Carroll, Camille;Bale, Claire;Grosset, Donald;Stafford, Eleanor J.;Houlden, Henry;Morris, Huw R.;Hardy, John;Mok, Kin Ying;Rizig, Mie;Wood, Nicholas;Williams, Nigel;Okunoye, Olaitan;Lewis, Patrick Alfryn;Kaiyrzhanov, Rauan;Weil, Rimona;Love, Seth;Stott, Simon;Jasaityte, Simona;Dey, Sumit;Obese, Vida;Espay, Alberto;O'Grady, Alyssa;Sobering, Andrew K.;Siddiqi, Bernadette;Casey, Bradford;Fiske, Brian;Jonas, Cabell;Cruchaga, Carlos;Pantazis, Caroline B.;Comart, Charisse;Wegel, Claire;Hall, Deborah;Hernandez, Dena;Shiamim, Ejaz;Riley, Ekemini;Faghri, Faraz;Serrano, Geidy E.;Chen, Honglei;Mata, Ignacio F.;Sarmiento, Ignacio Juan Keller;Williamson, Jared;Jankovic, Joseph;Shulman, Joshua;Solle, Justin C.;Murphy, Kaileigh;Nuytemans, Karen;Kieburtz, Karl;Markopoulou, Katerina;Marek, Kenneth;Levine, Kristin S.;Chahine, Lana M.;Ibanez, Laura;Screven, Laurel;Ruffrage, Lauren;Shulman, Lisa;Marsili, Luca;Kuhl, Maggie;Dean, Marissa;Koretsky, Mathew;Puckelwartz, Megan J.;Inca-Martinez, Miguel;Louie, Naomi;Mencacci, Niccolo Emanuele;Albin, Roger;Alcalay, Roy;Walker, Ruth;Chowdhury, Sohini;Dumanis, Sonya;Lubbe, Steven;Xie, Tao;Foroud, Tatiana;Beach, Thomas;Sherer, Todd;Song, Yeajin;Nguyen, Duan;Nguyen, Toan;Atadzhanov, Masharip;Blauwendraat, Cornelis;Nalls, Mike A.;Foo, Jia Nee;Mata, Ignacio
虽然使用全基因组关联研究已经确定了帕金森病的90多个独立风险变体，但大多数研究一次只在一个人群中进行。在这里，我们对帕金森病进行了一项大规模的多血统荟萃分析，其中包括49，049例病例，18，785例代理病例和2，458，063例对照，包括欧洲，东亚，拉丁美洲和非洲血统的个体。在一项荟萃分析中，我们确定了78个独立的全基因组显著位点，包括12个潜在的新位点（MTF 2，PIK3CA，ADD 1，SYBU，IRS2，USP 8，PIGL，FIGH，MYLK 2，USP 25，EP 300和PPP6R2）和6个已知PD位点的6个推定致病变异体。通过将我们的结果与公开的eQTL数据相结合，我们在这些新的基因座中鉴定了25个推定的风险基因，其表达与PD风险相关。这项工作奠定了基础，为今后的努力，旨在确定PD基因座在非欧洲人口。多祖先全基因组关联分析确定了帕金森病的新风险位点，精细定位和共定位分析涉及其表达与疾病易感性相关的候选基因。
Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations. Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.
登录
查看更多内容
影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
30.8
作者：
de Klein, Niek;Tsai, Ellen A.;Vochteloo, Martijn;Baird, Denis;Huang, Yunfeng;Chen, Chia-Yen;van Dam, Sipko;Oelen, Roy;Deelen, Patrick;Bakker, Olivier B.;El Garwany, Omar;Ouyang, Zhengyu;Marshall, Eric E.;Zavodszky, Maria I.;van Rheenen, Wouter;Bakker, Mark K.;Veldink, Jan;Gaunt, Tom R.;Runz, Heiko;Franke, Lude;Westra, Harm-Jan
通讯作者：
Westra, Harm-Jan
DOI：
10.1073/pnas.1318306111
发表时间：
2014-02-18
影响因子：
11.1
作者：
Beilina, Alexandria;Rudenko, Iakov N.;Cookson, Mark R.
通讯作者：
Cookson, Mark R.