Identification of risk loci for primary aldosteronism in genome-wide association studies.
Identification of risk loci for primary aldosteronism in genome-wide association studies.
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DOI：
10.1038/s41467-022-32896-8
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发表时间：
2022-09-03
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
原发性醛固酮增多症影响高达10%的高血压患者，并导致治疗抵抗和心血管风险增加。在这里，我们在562例病例和950例对照的发现队列中进行了全基因组关联研究，并确定了染色体1，13和X上的三个主要位点;染色体1和13上的关联在第二个队列中重复，并通过涉及1162例病例和3296例对照的荟萃分析证实。13号染色体上的关联是男性特有的，在双侧肾上腺增生中比醛固酮腺瘤更强。位于两个基因座内的候选基因CASZ 1和RXFP 2在人类和小鼠肾上腺的不同细胞簇中表达。它们在肾上腺皮质细胞中的过度表达在基础和刺激条件下抑制盐皮质激素输出，而不影响皮质醇生物合成。我们的研究确定了原发性醛固酮增多症的第一个危险位点，并强调了醛固酮过量发展的新机制。原发性醛固酮增多症是继发性动脉高血压的最常见形式，检测原发性醛固酮增多症对于有针对性的管理和预防心血管并发症至关重要。在这里，作者确定了与原发性醛固酮增多症相关的遗传位点，提出了疾病的新机制。
Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma. Candidate genes located within the two loci, CASZ1 and RXFP2, are expressed in human and mouse adrenals in different cell clusters. Their overexpression in adrenocortical cells suppresses mineralocorticoid output under basal and stimulated conditions, without affecting cortisol biosynthesis. Our study identifies the first risk loci for primary aldosteronism and highlights new mechanisms for the development of aldosterone excess. Detection of primary aldosteronism, the most common form of secondary arterial hypertension, is essential for targeted management and prevention of cardiovascular complications. Here, the authors identify genetic loci associated with primary aldosteronism, suggesting new mechanisms of disease.
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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：
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：
8.3
作者：
De Sousa, Kelly;Boulkroun, Sheerazed;Zennaro, Maria-Christina
通讯作者：
Zennaro, Maria-Christina
影响因子：
30.8
作者：
Azizan, Elena A. B.;Poulsen, Hanne;Brown, Morris J.
通讯作者：
Brown, Morris J.
影响因子：
30.8
作者：
Ehret, Georg B.;Ferreira, Teresa;Chasman, Daniel I.;Jackson, Anne U.;Schmidt, Ellen M.;Johnson, Toby;Thorleifsson, Gudmar;Luan, Jian'an;Donnelly, Louise A.;Kanoni, Stavroula;Petersen, Ann -Kristin;Pihurl, Vasyl;Strawbridge, Rona J.;Shungin, Dmitry;Hughes, Maria F.;Meirelles, Osorio;Kaakinen, Marika;Bouatia-Naji, Nabila;Kristiansson, Kati;Shah, Sonia;Kleber, Marcus E.;Guo, Xiuqing;Lyytikainen, Leo-Pekka;Fava, Cristiano;Eriksson, Nidas;Nolte, Ilja M.;Magnusson, Patrik K.;Salfati, Elias L.;Rallidis, Loukianos S.;Theusch, Elizabeth;Smith, Andrew J. P.;Folkersen, Lasse;Witkowska, Kate;Pers, Tune H.;Joehanes, Roby;Kim, Stuart K.;Lataniotis, Lazaros;Jansen, Rick;Johnson, Andrew D.;Warren, Helen;Kim, Young Jin;Zhao, Wei;Wu, Ying;Tayo, Bamidele O.;Bochud, Murielle;Absher, Devin;Adair, Linda S.;Amin, Najaf;Arkingl, Dan E.;Axelsson, Tomas;Baldassarre, Damian;Balkau, Beverley;Bandinelli, Stefania;Barnes, Michael R.;Barroso, Ines;Bevan, Stephen;Bis, Joshua C.;Bjornsdottir, Gyda;Boehnke, Michael;Boerwinkle, Eric;Bonnycastle, Lori L.;Boomsma, Dorret I.;Bornstein, Stefan R.;Brown, Morris J.;Burnier, Michel;Cabrera, Claudia P.;Chambers, John C.;Chang, I-Shou;Cheng, Ching-Yu;Chines, Peter S.;Chung, Ren-Hua;Collins, Francis S.;Connell, John M.;Doring, Angela;Dallongeville, Jean;Danesh, John;de Faire, Ulf;Delgado, Graciela;Dominiczak, Anna F.;Doney, Alex S. F.;Drenos, Fotios;Edkins, Sarah;Eicher, John D.;Elosua, Roberto;Enroth, Stefan;Erdmann, Jeanette;Eriksson, Per;Esko, Tonu;Evangelou, Evangelos;Evans, Alun;Fai, Tove;Farra, Martin;Felixl, Janine F.;Ferrieres, Jean;Ferrucci, Luigi;Fornage, Myriam;Forrester, Terrence;Franceschinil, Nora;Franco, Oscar H.;Franco-Cereceda, Anders;Fraser, Ross M.;Ganesh, Santhi K.;Gao, He;Gertow, Karl;Gianfagna, Francesco;Gigante, Bruna;Giulianini, Franco;Goe, Anuj;Goodall, Alison H.;Goodarzi, Mark;Gorski, Mathias;Grassler, Jurgen;Groves, Christopher J.;Gudnason, Vilmundur;Gyllensten, Ulf;Hallmans, Goran;Hartikainen, Anna-Liisa;Hassinen, Maija;Havulinna, Aki S.;Hayward, Caroline;Hercberg, Serge;Herzig, Karl-Heinz;Hicks, Andrew A.;Hingorani, Aroon D.;Hirschhorn, Joel N.;Hofmanl, Albert;Holmen, Jostein;Holmen, Oddgeir Lingaas;Hottenga, Jouke-Jan;Howard, Phil;Hsiung, Chao A.;Hunt, Steven C.;Ikram, M. Arfan;Illig, Thomas;Iribarren, Carlos;Jensen, Richard A.;Kahonen, Mika;Kang, Hyun Min;Kathiresan, Sekar;Keating, Brendan J.;Khaw, Kay-Tee;Kim, Yun Kyoung;Kim, Eric;Kivimaki, Mika;Klopp, Norman;Kolovou, Genovefa;Komulainen, Pirjo;Kooner, Jaspal S.;Kosova, Gulum;Krauss, Ronald M.;Kuh, Diana;Kutalik, Zoltan;Kuusisto, Johanna;Kvaloy, Kirsti;Lakka, Timo A.;Lee, Nanette R.;Lee, I-Te;Lee, Wen-Jane;Levy, Daniel;Li, Xiaohui;Liang, Kae-Woei;Lin, Honghuang;Lin, Li;Lindstrom, Jaana;Lobbens, Stephane;Mannisto, Satu;Muller, Gabriele;Muller-Nurasyid, Martina;Mach, Francois;Markus, Hugh S.;Marouli, Eirini;McCarthy, Mark I.;McKenzie, Colin A.;Meneton, Pierre;Menni, Cristina;Metspalu, Andres;Mijatovic, Vladan;Moilanen, Leena;Montasser, May E.;Morris, Andrew D.;Morrison, Alanna C.;Mulas, Antonella;Nagaraja, Ramaiah;Narisu, Narisu;Nikus, Kjell;O'Donnell, Christopher J.;O'Reilly, Paul F.;Ong, Ken K.;Paccaud, Fred;Palmer, Cameron D.;Parsa, Afshin;Pedersen, Nancy L.;Penninx, Brenda W.;Perola, Markus;Peters, Annette;Poulter, Neil;Pramstaller, Peter P.;Psaty, Bruce M.;Quertermous, Thomas;Rao, Dabeeru C.;Rasheed, Asif;Rayner, N. William;Renstrom, Frida;Rettig, Rainer;Rice, Kenneth M.;Roberts, Robert;Rose, Lynda M.;Rossouw, Jacques;Samani, Nilesh J.;Sanna, Serena;Saramies, Jouko;Schunkert, Heribert;Sebert, Sylvain;Sheu, Wayne H-H;Shin, Young-Ah;Sim, Xueling;Smit, Johannes H.;Smith, Albert V.;Sosa, Maria X.;Spector, Tim D.;Stancakova, Alena;Stanton, Alice V.;Stirrups, Kathleen E.;Stringham, Heather M.;Sundstrom, Johan;Swift, Amy J.;Syvanen, Ann-Christine;Tai, E-Shyong;Tanaka, Toshiko;Tarasov, Kirill V.;Teumer, Alexander;Thorsteinsdottir, Unnur;Tobin, Martin D.;Tremoli, Elena;Uitterlinden, Andre G.;Uusitupa, Matti;Vaez, Ahmad;Vaidya, Dhananjay;van Duijn, Cornelia M.;van Iperen, Erik P. A.;Vasan, Ramachandran S.;Verwoert, Germaine C.;Virtamo, Jarmo;Vitart, Veronique;Voight, Benjamin F.;Vollenweider, Peter;Wagner, Aline;Wain, Louise V.;Wareham, Nicholas J.;Watldns, Hugh;Weder, Alan B.;Westra, Harm Jan;Wilks, Rainford;Wilsgaard, Tom;Wilson, James F.;Wong, Tien Y.;Yang, Tsun-Po;Yao, Jie;Yengo, Loic;Zhang, Weihua;Zhao, Jing Hua;Zhu, Xiaofeng;Bovet, Pascal;Cooper, Richard S.;Mohlke, Karen L.;Saleheen, Danish;Lee, Jong-Young;Elliott, Paul;Gierman, Hinco J.;Willer, Cristen J.;Franke, Lude;Hovingh, G. Kees;Taylor, Kent D.;Dedoussis, George;Sever, Peter;Wong, Andrew;Lind, Lars;Assimes, Themistocles L.;Njolstad, Inger;Schwarz, Peter E. H.;Langenberg, Claudia;Snieder, Harold;Caulfield, Mark J.;Melander, E.;Laakso, Markku;Saltevo, Juha;Rauramaa, Rainer;Tuomilehto, Jaakko;Ingelsson, Erik;Lehtimaki, Terho;Hveem, Kristian;Palmas, Walter;Marz, Winfried;Kumar, Meena;Salomaa, Veikko;Chen, Yii-Der I.;Rotter, Jerome I.;Froguel, Philippe;Jarvelin, Marjo-Riitta;Lakatta, Edward G.;Kuulasmaa, Kari;Franks, Paul W.;Hamsten, Anders;Wichmann, H-Erich;Palmer, Colin N. A.;Stefansson, Kari;Ridker, Paul M.;Loos, Ruth J. F.;Chalcravarti, Aravinda;Deloukas, Panos;Morris, Andrew P.;Newton-Cheh, Christopher;Munroe, Patricia B.
通讯作者：
Munroe, Patricia B.