Characterizing the Genetic Architecture of Parkinson's Disease in Latinos.
Characterizing the Genetic Architecture of Parkinson's Disease in Latinos.
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表征拉丁美洲帕金森病的遗传结构。
DOI：
10.1002/ana.26153
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发表时间：
2021-09
影响因子：
11.2
通讯作者：
Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)
中科院分区：
文献类型：
--
作者：
Loesch DP;Horimoto ARVR;Heilbron K;Sarihan EI;Inca-Martinez M;Mason E;Cornejo-Olivas M;Torres L;Mazzetti P;Cosentino C;Sarapura-Castro E;Rivera-Valdivia A;Medina AC;Dieguez E;Raggio V;Lescano A;Tumas V;Borges V;Ferraz HB;Rieder CR;Schumacher-Schuh A;Santos-Lobato BL;Velez-Pardo C;Jimenez-Del-Rio M;Lopera F;Moreno S;Chana-Cuevas P;Fernandez W;Arboleda G;Arboleda H;Arboleda-Bustos CE;Yearout D;Zabetian CP;23andMe Research Team;Cannon P;Thornton TA;O'Connor TD;Mata IF;Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)
这项工作是为了确定帕金森病（PD）的风险变异在拉丁裔队列，描述的重叠在遗传结构的PD在拉丁裔相比，欧洲血统的主题，并增加PD全基因组关联（GWAS）数据的多样性。我们对从南美9个临床研究中心招募的1497例PD病例和对照进行了基因分型和插补。我们使用logistic混合模型进行了GWAS;在来自23andMe，Inc.的1，234例自我报告的拉丁裔PD病例和439，522例拉丁裔对照的重复队列中检验了p值< 1×10−5的变异。我们还进行了混合映射分析，其中测试了当地血统区块与PD状态的关联。一个位点SNCA实现了全基因组意义（p值< 5×10−8）; rs356182在发现和复制队列中都具有全基因组意义（发现，G等位基因：1.58 OR，95% CI 1.35-1.86，p值2.48×10−8; 23和Me，G等位基因：1.26 OR，95% CI 1.16-1.37，p值4.55×10−8）。在我们的混合作图分析中，14号染色体上的一个位点，包含基因STXBP 6，在祖先的联合检验和美洲原住民单祖先检验中达到了显著性（p值< 5×10−5）。第二个位于6号染色体上的基因位点，包含基因RPS 6 KA 2，在非洲单祖先测试中达到显著性（p值< 5×10−5）。这项研究证明了SNCA基因座的重要性，在拉丁美洲的PD病因。通过利用我们队列的人口统计学历史，通过混合物映射，我们确定了两个潜在的PD风险位点，值得进一步研究。
This work was undertaken in order to identify Parkinson’s disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data. We genotyped and imputed 1497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p-value < 1×10−5 were tested in a replication cohort of 1,234 self-reported Latino PD cases and 439,522 Latino controls from 23andMe, Inc. We also performed an admixture mapping analysis where local ancestry blocks were tested for association with PD status. One locus, SNCA, achieved genome-wide significance (p-value < 5×10−8); rs356182 achieved genome-wide significance in both the discovery and the replication cohorts (discovery, G allele: 1.58 OR, 95% CI 1.35–1.86, p-value 2.48×10−8; 23andMe, G allele: 1.26 OR, 95% CI 1.16–1.37, p-value 4.55×10−8). In our admixture mapping analysis, a locus on chromosome 14, containing the gene STXBP6, achieved significance in a joint test of ancestries and in the Native American single-ancestry test (p-value < 5×10−5). A second locus on chromosome 6, containing the gene RPS6KA2, achieved significance in the African single-ancestry test (p-value < 5×10−5). This study demonstrated the importance of the SNCA locus for the etiology of PD in Latinos. By leveraging the demographic history of our cohort via admixture mapping, we identified two potential PD risk loci that merit further study.
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影响因子：
5.8
作者：
Gogarten, Stephanie M.;Sofer, Tamar;Conomos, Matthew P.
通讯作者：
Conomos, Matthew P.
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
2.1
作者：
Conomos MP;Miller MB;Thornton TA
通讯作者：
Thornton TA