The genetics and functional analysis of primary osteoarthritis susceptibility.
The genetics and functional analysis of primary osteoarthritis susceptibility.
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DOI：
10.1017/erm.2013.4
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发表时间：
2013-02-18
影响因子：
6.2
通讯作者：
Loughlin J
中科院分区：
文献类型：
--
作者：
Reynard LN;Loughlin J
最近的全基因组关联扫描（GWAS）沿着几个充分有力的候选基因研究，已经产生了许多骨关节炎（OA）的风险等位基因。这个数字现在已经足够大，可以得出关于遗传易感性的性质的结论，包括风险等位基因根据性别、种族和疾病的骨骼部位而具有可变影响的事实。从GWAS中出现的几个等位基因在高度合理的候选基因内或接近高度合理的候选基因，包括RUNX2和CHST 11。然而，大多数风险等位基因并没有映射到先前报道的在肌肉骨骼生物学中发挥作用的基因，这表明GWAS数据集告诉我们关于OA疾病过程的新信息。迄今为止，功能研究表明，对基因表达的影响可能是OA易感性的主要作用机制之一。DNA甲基化等表观遗传机制也会影响OA风险，遗传、转录组和表观遗传数据的整合将使我们能够利用遗传发现来开发新的OA生物治疗方法。
Recent genome-wide association scans (GWASs) along with several adequately powered candidate gene studies have yielded a number of risk alleles for osteoarthritis (OA). This number is now sufficiently large to allow conclusions to be drawn regarding the nature of genetic susceptibility, including the fact that the risk alleles have variable effects depending on sex, ethnicity and on the skeletal site of the disease. Several of the alleles that have emerged from the GWASs are within or close to highly plausible candidate genes, including RUNX2 and CHST11. However, the majority of risk alleles do not map to genes previously reported to play a role in musculoskeletal biology, indicating that the GWAS datasets are telling us something new about the OA disease process. Functional studies have so far revealed that effects on gene expression are likely to be one of the main mechanisms through which OA susceptibility is acting. Epigenetic mechanisms such as DNA methylation also influence OA risk, and integration of genetic, transcriptomic and epigenetic data will allow us to use the genetic discoveries for informed development of new OA biological treatments.
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影响因子：
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作者：
Evangelou, Evangelos;Chapman, Kay;Meulenbelt, Ingrid;Karassa, Fotini B.;Loughlin, John;Carr, Andrew;Doherty, Michael;Doherty, Sally;Gomez-Reino, Juan J.;Gonzalez, Antonio;Halldorsson, Bjarni V.;Hauksson, Valdimar B.;Hofman, Albert;Hart, Deborah J.;Ikegawa, Shiro;Ingvarsson, Thorvaldur;Jiang, Qing;Jonsdottir, Ingileif;Jonsson, Helgi;Kerkhof, Hanneke J. M.;Kloppenburg, Margreet;Lane, Nancy E.;Li, Jia;Lories, Rik J.;van Meurs, Joyce B. J.;Nakki, Annu;Nevitt, Michael C.;Rodriguez-Lopez, Julio;Shi, Dongquan;Slagboom, Eline;Stefansson, Kari;Tsezou, Aspasia;Wallis, Gillian A.;Watson, Christopher M.;Spector, Tim D.;Uitterlinden, Andre G.;Valdes, Ana M.;Ioannidis, John P. A.
通讯作者：
Ioannidis, John P. A.
影响因子：
27.4
作者：
Hudson G;Panoutsopoulou K;Wilson I;Southam L;Rayner NW;Arden N;Birrell F;Carluke I;Carr A;Chapman K;Deloukas P;Doherty M;McCaskie A;Ollier WE;Ralston SH;Reed MR;Spector TD;Valdes AM;Wallis GA;Wilkinson JM;Zeggini E;Samuels DC;Loughlin J;Chinnery PF;arcOGEN Consortium
通讯作者：
arcOGEN Consortium
DOI：
10.1126/science.1217283
发表时间：
2012-05-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Keinan A;Clark AG
通讯作者：
Clark AG
一项全基因组关联研究确定了7q22染色体上的骨关节炎易感性基因座。
影响因子：
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作者：
Kerkhof, Hanneke J. M.;Lories, Rik J.;Meulenbelt, Ingrid;Jonsdottir, Ingileif;Valdes, Ana M.;Arp, Pascal;Ingvarsson, Thorvaldur;Jhamai, Mila;Jonsson, Helgi;Stolk, Lisette;Thorleifsson, Gudmar;Zhai, Guangju;Zhang, Feng;Zhu, Yanyan;van der Breggen, Ruud;Carr, Andrew;Doherty, Michael;Doherty, Sally;Felson, David T.;Gonzalez, Antonio;Halldorsson, Bjarni V.;Hart, Deborah J.;Hauksson, Valdimar B.;Hofman, Albert;Ioannidis, John P. A.;Kloppenburg, Margreet;Lane, Nancy E.;Loughlin, John;Luyten, Frank P.;Nevitt, Michael C.;Parimi, Neeta;Pols, Huibert A. P.;Rivadeneira, Fernando;Slagboom, Eline P.;Styrkarsdottir, Unnur;Tsezou, Aspasia;van de Putte, Tom;Zmuda, Joseph;Spector, Tim D.;Stefansson, Kari;Uitterlinden, Andre G.;van Meurs, Joyce B. J.
通讯作者：
van Meurs, Joyce B. J.
影响因子：
3.5
作者：
Chapman, Kay;Takahashi, Atsushi;Ikegawa, Shiro
通讯作者：
Ikegawa, Shiro