A mega-analysis of genome-wide association studies for major depressive disorder.
A mega-analysis of genome-wide association studies for major depressive disorder.
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DOI：
10.1038/mp.2012.21
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发表时间：
2013-04
影响因子：
11
通讯作者：
Viktorin, Alexander
中科院分区：
文献类型：
--
作者：
Sullivan, Patrick F.;Daly, Mark J.;Ripke, Stephan;Lewis, Cathryn M.;Lin, Dan-Yu;Wray, Naomi R.;Neale, Benjamin;Levinson, Douglas F.;Breen, Gerome;Byrne, Enda M.;Wray, Naomi R.;Levinson, Douglas F.;Rietschel, Marcella;Hoogendijk, Witte;Ripke, Stephan;Sullivan, Patrick F.;Hamilton, Steven P.;Levinson, Douglas F.;Lewis, Cathryn M.;Ripke, Stephan;Weissman, Myrna M.;Wray, Naomi R.;Breuer, Rene;Cichon, Sven;Degenhardt, Franziska;Frank, Josef;Gross, Magdalena;Herms, Stefan;Hoefels, Susanne;Maier, Wolfgang;Mattheisen, Manuel;Noeethen, Markus M.;Rietschel, Marcella;Schulze, Thomas G.;Steffens, Michael;Treutlein, Jens;Boomsma, Dorret I.;De Geus, Eco J.;Hoogendijk, Witte;Hottenga, Jouke Jan;Jung-Ying, Tzeng;Lin, Dan-Yu;Middeldorp, Christel M.;Nolen, Willem A.;Penninx, Brenda P.;Smit, Johannes H.;Sullivan, Patrick F.;van Grootheest, Gerard;Willemsen, Gonneke;Zitman, Frans G.;Coryell, William H.;Knowles, James A.;Lawson, William B.;Levinson, Douglas F.;Potash, James B.;Scheftner, William A.;Shi, Jianxin;Weissman, Myrna M.;Holsboer, Florian;Muglia, Pierandrea;Tozzi, Federica;Blackwood, Douglas H. R.;Boomsma, Dorret I.;De Geus, Eco J.;Hottenga, Jouke Jan;MacIntyre, Donald J.;McIntosh, Andrew;McLean, Alan;Middeldorp, Christel M.;Nolen, Willem A.;Penninx, Brenda P.;Ripke, Stephan;Smit, Johannes H.;Sullivan, Patrick F.;van Grootheest, Gerard;Willemsen, Gonneke;Zitman, Frans G.;van den Oord, Edwin J. C. G.;Holsboer, Florian;Lucae, Susanne;Binder, Elisabeth;Mueller-Myhsok, Bertram;Ripke, Stephan;Czamara, Darina;Kohli, Martin A.;Ising, Marcus;Uhr, Manfred;Bettecken, Thomas;Barnes, Michael R.;Breen, Gerome;Craig, Ian W.;Farmer, Anne E.;Lewis, Cathryn M.;McGuffin, Peter;Muglia, Pierandrea;Byrne, Enda;Gordon, Scott D.;Heath, Andrew C.;Henders, Anjali K.;Hickie, Ian B.;Madden, Pamela A. F.;Martin, Nicholas G.;Montgomery, Grant M.;Nyholt, Dale R.;Pergadia, Michele L.;Wray, Naomi R.;Hamilton, Steven P.;McGrath, Patrick J.;Shyn, Stanley I.;Slager, Susan L.;Oskarsson, Hoegni;Sigurdsson, Engilbert;Stefansson, Hreinn;Stefansson, Kari;Steinberg, Stacy;Thorgeirsson, Thorgeir;Levinson, Douglas F.;Potash, James B.;Shi, Jianxin;Weissman, Myrna M.;Guipponi, Michel;Lewis, Glyn;O'Donovan, Michael;Tansey, Katherine E.;Uher, Rudolf;Coryell, William H.;Knowles, James A.;Lawson, William B.;Levinson, Douglas F.;Potash, James B.;Scheftner, William A.;Shi, Jianxin;Weissman, Myrna M.;Castro, Victor M.;Churchill, Susanne E.;Fava, Maurizio;Gainer, Vivian S.;Gallagher, Patience J.;Goryachev, Sergey;Iosifescu, Dan V.;Kohane, Isaac S.;Murphy, Shawn N.;Perlis, Roy H.;Smoller, Jordan W.;Weilburg, Jeffrey B.;Kutalik, Zoltan;Preisig, Martin;Grabe, Hans J.;Nauck, Matthias;Schulz, Andrea;Teumer, Alexander;Voelzke, Henry;Landen, Mikael;Lichtenstein, Paul;Magnusson, Patrik;Pedersen, Nancy;Viktorin, Alexander
先前对重度抑郁障碍(MDD)的全基因组关联研究(GWAS)仅取得了有限的成功。我们试图通过对MDD进行GWA超大型分析来增加检测疾病位点的统计能力。在MDD发现阶段，我们分析了18759名独立和无关的近期欧洲血统受试者(9240例MDD病例和9519名对照)中超过120万个常染色体和X染色体单核苷酸多态(SNPs)。在MDD复制阶段，我们评估了独立样本中的554个SNP(6783例MDD病例和50695名对照)。我们还利用P<；0.0001的819个常染色体SNPs对MDD或精神病学双相情感障碍进行了交叉疾病荟萃分析(9238例MDD/8039例对照和6998例BIP/7775对照)。在MDD发现阶段、MDD复制阶段或预先计划的二次分析(按性别、复发MDD、复发早发性MDD、发病年龄、青春期前MDD或根据MDD标准的潜伏类分析得出的典型MDD)中，没有SNPs获得全基因组意义。在MDD-双极交叉分析中，有15个SNP超过全基因组意义(P<；5×10−8)，均位于3p21.1的248kb高LD区间(Chr3：52 425 083-53 822 102，最小P=5.9×10−9，位于rs2535629)。尽管这是迄今为止对MDD进行的最大规模的全基因组分析，但它的高流行率意味着样本仍然没有能力检测复杂特征的典型遗传效应。因此，我们无法确定可靠和可复制的发现。我们讨论了这对MDD的基因研究意味着什么。应谨慎解释3p21.1 MDD-BIP发现，因为最重要的SNP没有在MDD样本中复制，需要在独立样本中进行基因分型以解决其状态。
Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P< 0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5×10−8), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083–53 822 102, minimum P= 5.9×10−9 at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.
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COLAUS研究：一项基于人群的研究，旨在研究心血管危险因素和代谢综合征的流行病学和遗传决定因素。
影响因子：
2.1
作者：
Firmann, Mathieu;Mayor, Vladimir;Vidal, Pedro Marques;Bochud, Murielle;Pecoud, Alain;Hayoz, Daniel;Paccaud, Fred;Preisig, Martin;Song, Kijoung S.;Yuan, Xin;Danoff, Theodore M.;Stirnadel, Heide A.;Waterworth, Dawn;Mooser, Vincent;Waeber, Gerard;Vollenweider, Peter
通讯作者：
Vollenweider, Peter
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
de Bakker, Paul I. W.;Ferreira, Manuel A. R.;Voight, Benjamin F.
通讯作者：
Voight, Benjamin F.
DOI：
10.1073/pnas.0903103106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Hindorff, Lucia A.;Sethupathy, Praveen;Manolio, Teri A.
通讯作者：
Manolio, Teri A.