High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.
High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.
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DOI：
10.1038/ng.2462
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发表时间：
2012-12
期刊：
影响因子：
30.8
通讯作者：
Worthington, Jane
中科院分区：
文献类型：
--
作者：
Eyre, Steve;Bowes, John;Diogo, Dorothee;Lee, Annette;Barton, Anne;Martin, Paul;Zhernakova, Alexandra;Stahl, Eli;Viatte, Sebastien;McAllister, Kate;Amos, Christopher I.;Padyukov, Leonid;Toes, Rene E. M.;Huizinga, Tom W. J.;Wijmenga, Cisca;Trynka, Gosia;Franke, Lude;Westra, Harm-Jan;Alfredsson, Lars;Hu, Xinli;Sandor, Cynthia;de Bakker, Paul I. W.;Davila, Sonia;Khor, Chiea Chuen;Heng, Khai Koon;Andrews, Robert;Edkins, Sarah;Hunt, Sarah E.;Langford, Cordelia;Symmons, Deborah;Concannon, Pat;Onengut-Gumuscu, Suna;Rich, Stephen S.;Deloukas, Panos;Gonzalez-Gay, Miguel A.;Rodriguez-Rodriguez, Luis;Arlsetig, Lisbeth;Martin, Javier;Rantapaa-Dahlqvist, Solbritt;Plenge, Robert M.;Raychaudhuri, Soumya;Klareskog, Lars;Gregersen, Peter K.;Worthington, Jane
使用免疫芯片定制单核苷酸多态性（SNP）阵列，设计用于186个全基因组关联研究（GWAS）确认的基因座的密集基因分型，我们分析了11，475例欧洲血统的类风湿性关节炎病例和15，870例对照的129，464个标记。在荟萃分析中，这些数据与来自额外独立病例（n= 2，363）和对照组（n= 17，872）的GWAS数据相结合。我们确定了14个新的基因座，其中9个与类风湿性关节炎相关，5个与抗柠檬酸肽抗体阳性疾病相关，使确认的欧洲祖先类风湿性关节炎基因座数量达到46个。我们对19个基因座与单个基因的关联峰值进行了细化，在6个基因座鉴定了次要独立效应，在4个基因座鉴定了与低频变异（次要等位基因频率<0.05）的关联。对数据的生物信息学分析产生了七个位点的因果SNP的强有力的假设。这项研究说明了密集SNP定位分析的优势，为后续的功能研究提供信息。
Using the Immunochip custom single nucleotide polymorphism (SNP) array, designed for dense genotyping of 186 genome wide association study (GWAS) confirmed loci we analysed 11,475 rheumatoid arthritis cases of European ancestry and 15,870 controls for 129,464 markers. The data were combined in meta-analysis with GWAS data from additional independent cases (n=2,363) and controls (n=17,872). We identified fourteen novel loci; nine were associated with rheumatoid arthritis overall and 5 specifically in anti-citrillunated peptide antibody positive disease, bringing the number of confirmed European ancestry rheumatoid arthritis loci to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at six loci and association to low frequency variants (minor allele frequency <0.05) at 4 loci. Bioinformatic analysis of the data generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.
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影响因子：
168.9
作者：
Ferreira, Manuel A. R.;Matheson, Melanie C.;Duffy, David L.;Marks, Guy B.;Hui, Jennie;Le Souef, Peter;Danoy, Patrick;Baltic, Svetlana;Nyholt, Dale R.;Jenkins, Mark;Hayden, Catherine;Willemsen, Gonneke;Ang, Wei;Kuokkanen, Mikko;Beilby, John;Cheah, Faang;de Geus, Eco J. C.;Ramasamy, Adaikalavan;Vedantam, Sailaja;Salomaa, Veikko;Madden, Pamela A.;Heath, Andrew C.;Hopper, John L.;Visscher, Peter M.;Musk, Bill;Leeder, Stephen R.;Jarvelin, Marjo-Riitta;Pennell, Craig;Boomsma, Dorret I.;Hirschhorn, Joel N.;Walters, Haydn;Martin, Nicholas G.;James, Alan;Jones, Graham;Abramson, Michael J.;Robertson, Colin F.;Dharmage, Shyamali C.;Brown, Matthew A.;Montgomery, Grant W.;Thompson, Philip J.
通讯作者：
Thompson, Philip J.
影响因子：
30.8
作者：
通讯作者：
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Suzuki, A;Yamada, R;Yamamoto, K
通讯作者：
Yamamoto, K
影响因子：
9.8
作者：
Hu, Xinli;Kim, Hyun;Raychaudhuri, Soumya
通讯作者：
Raychaudhuri, Soumya