Genome-wide association of phenotypes based on clustering patterns of hand osteoarthritis identify WNT9A as novel osteoarthritis gene.
Genome-wide association of phenotypes based on clustering patterns of hand osteoarthritis identify WNT9A as novel osteoarthritis gene.
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DOI：
10.1136/annrheumdis-2020-217834
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发表时间：
2021-03
影响因子：
27.4
通讯作者：
van Meurs JB
中科院分区：
文献类型：
--
作者：
Boer CG;Yau MS;Rice SJ;Coutinho de Almeida R;Cheung K;Styrkarsdottir U;Southam L;Broer L;Wilkinson JM;Uitterlinden AG;Zeggini E;Felson D;Loughlin J;Young M;Capellini TD;Meulenbelt I;van Meurs JB
Despite recent advances in the understanding of the genetic architecture of osteoarthritis (OA), only two genetic loci have been identified for OA of the hand, in part explained by the complexity of the different hand joints and heterogeneity of OA pathology. We used data from the Rotterdam Study (RSI, RSII and RSIII) to create three hand OA phenotypes based on clustering patterns of radiographic OA severity to increase power in our modest discovery genome-wide association studies in the RS (n=8700), and sought replication in an independent cohort, the Framingham Heart Study (n=1203). We used multiple approaches that leverage different levels of information and functional data to further investigate the underlying biological mechanisms and candidate genes for replicated loci. We also attempted to replicate known OA loci at other joint sites, including the hips and knees. We found two novel genome-wide significant loci for OA in the thumb joints. We identified WNT9A as a possible novel causal gene involved in OA pathogenesis. Furthermore, several previously identified genetic loci for OA seem to confer risk for OA across multiple joints: TGFa, RUNX2, COL27A1, ASTN2, IL11 and GDF5 loci. We identified a robust novel genetic locus for hand OA on chromosome 1, of which WNT9A is the most likely causal gene. In addition, multiple genetic loci were identified to be associated with OA across multiple joints. Our study confirms the potential for novel insight into the genetic architecture of OA by using biologically meaningful stratified phenotypes.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
27.4
作者：
Bijsterbosch, J.;Watt, I.;Kloppenburg, M.
通讯作者：
Kloppenburg, M.
影响因子：
27.4
作者：
Kjeken, I;Dagfinrud, H;Finset, A
通讯作者：
Finset, A
DOI：
10.1002/art.40748
发表时间：
2019-04
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
den Hollander W;Pulyakhina I;Boer C;Bomer N;van der Breggen R;Arindrarto W;Couthino de Almeida R;Lakenberg N;Sentner T;Laros JFJ;'t Hoen PAC;Slagboom EPE;Nelissen RGHH;van Meurs J;Ramos YFM;Meulenbelt I
通讯作者：
Meulenbelt I
全基因组的关联和功能研究确定了基质gla蛋白在手的骨关节炎中的作用。
影响因子：
27.4
作者：
den Hollander W;Boer CG;Hart DJ;Yau MS;Ramos YFM;Metrustry S;Broer L;Deelen J;Cupples LA;Rivadeneira F;Kloppenburg M;Peters M;Spector TD;Hofman A;Slagboom PE;Nelissen RGHH;Uitterlinden AG;Felson DT;Valdes AM;Meulenbelt I;van Meurs JJB
通讯作者：
van Meurs JJB