Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification.
Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification.
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多功能全基因组研究确定了冠状动脉钙化的效应基因和可药的途径。
DOI：
10.1038/s41588-023-01518-4
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发表时间：
2023-10
期刊：
影响因子：
30.8
通讯作者：
Miller, Clint L.
中科院分区：
文献类型：
--
作者：
Kavousi, Maryam;Bos, Maxime M.;Barnes, Hanna J.;Cardenas, Christian L. Lino;Wong, Doris;Lu, Haojie;Hodonsky, Chani J.;Landsmeer, Lennart P. L.;Turner, Adam W.;Kho, Minjung;Hasbani, Natalie R.;de Vries, Paul S.;Bowden, Donald W.;Chopade, Sandesh;Deelen, Joris;Benavente, Ernest Diez;Guo, Xiuqing;Hofer, Edith;Hwang, Shih-Jen;Lutz, Sharon M.;Lyytikainen, Leo-Pekka;Slenders, Lotte;Smith, Albert V.;Stanislawski, Maggie A.;van Setten, Jessica;Wong, Quenna;Yanek, Lisa R.;Becker, Diane M.;Beekman, Marian;Budoff, Matthew J.;Feitosa, Mary F.;Finan, Chris;Hilliard, Austin T.;Kardia, Sharon L. R.;Kovacic, Jason C.;Kral, Brian G.;Langefeld, Carl D.;Launer, Lenore J.;Malik, Shaista;Hoesein, Firdaus A. A. Mohamed;Mokry, Michal;Schmidt, Reinhold;Smith, Jennifer A.;Taylor, Kent D.;Terry, James G.;van der Grond, Jeroen;van Meurs, Joyce;Vliegenthart, Rozemarijn;Xu, Jianzhao;Young, Kendra A.;Zilhao, Nuno R.;Zweiker, Robert;Assimes, Themistocles L.;Becker, Lewis C.;Bos, Daniel;Carr, J. Jeffrey;Cupples, L. Adrienne;de Kleijn, Dominique P. V.;de Winther, Menno;den Ruijter, Hester M.;Fornage, Myriam;Freedman, Barry I.;Gudnason, Vilmundur;Hingorani, Aroon D.;Hokanson, John E.;Ikram, M. Arfan;Isgum, Ivana;Jacobs, David R., Jr.;Kahonen, Mika;Lange, Leslie A.;Lehtimaki, Terho;Pasterkamp, Gerard;Raitakari, Olli T.;Schmidt, Helena;Slagboom, P. Eline;Uitterlinden, Andre G.;Vernooij, Meike W.;Bis, Joshua C.;Franceschini, Nora;Psaty, Bruce M.;Post, Wendy S.;Rotter, Jerome I.;Bjorkegren, Johan L. M.;O'Donnell, Christopher J.;Bielak, Lawrence F.;Peyser, Patricia A.;Malhotra, Rajeev;van der Laan, Sander W.;Miller, Clint L.
冠状动脉钙化（CAC）是亚临床动脉粥样硬化的一个指标，可以预测未来的症状性冠状动脉疾病（CAD）。确定CAC的遗传风险因素可能为预防CAC提供新的治疗途径。目前，在普通人群中，仅从全基因组关联研究（GWAS）中确定了4个已知的CAC风险位点。在这里，我们进行了迄今为止最大规模的CAC多祖先GWAS荟萃分析，其中包括26,909名欧洲血统个体和8,867名非洲血统个体。我们确定了11个独立的风险位点，其中8个是CAC的新基因，5个是CAD的未报道基因。这些新的CAC位点与骨矿化、磷酸盐分解代谢和激素代谢途径有关。多个功能证据支持的几个新基因座包含候选因果基因，并且是平滑肌细胞介导的体内和体外钙化的调节因子。总之，这些发现有助于完善CAC的遗传结构，并扩展我们对CAC的生物学和潜在药物通路的理解。
Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only 4 known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here, we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which 8 are novel for CAC and 5 have not been reported for CAD. These novel CAC loci are related to bone mineralization, phosphate catabolism, and hormone metabolic pathways. Several novel loci harbor candidate causal genes supported by multiple lines of functional evidence and are regulators of smooth muscle cell-mediated calcification ex vivo and in vitro. Together, these findings help refine the genetic architecture of CAC, and extend our understanding of the biological and potential druggable pathways underlying CAC.
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DOI：
10.2215/cjn.05080422
发表时间：
2023-01-01
期刊：
Clinical journal of the American Society of Nephrology : CJASN
影响因子：
--
作者：
Donovan K;Herrington WG;Paré G;Pigeyre M;Haynes R;Sardell R;Butterworth AS;Folkersen L;Gustafsson S;Wang Q;Baigent C;Mälarstig A;Holmes MV;Staplin N;on behalf of the SCALLOP Consortium
通讯作者：
on behalf of the SCALLOP Consortium
DOI：
10.1126/science.aad6970
发表时间：
2016-08-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franzén O;Ermel R;Cohain A;Akers NK;Di Narzo A;Talukdar HA;Foroughi-Asl H;Giambartolomei C;Fullard JF;Sukhavasi K;Köks S;Gan LM;Giannarelli C;Kovacic JC;Betsholtz C;Losic B;Michoel T;Hao K;Roussos P;Skogsberg J;Ruusalepp A;Schadt EE;Björkegren JL
通讯作者：
Björkegren JL
影响因子：
10.8
作者：
Durham AL;Speer MY;Scatena M;Giachelli CM;Shanahan CM
通讯作者：
Shanahan CM
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：
Fulco, Charles P.;Nasser, Joseph;Engreitz, Jesse M.
通讯作者：
Engreitz, Jesse M.