Follow-up association study of linkage regions reveals multiple candidate genes for carotid plaque in Dominicans.
Follow-up association study of linkage regions reveals multiple candidate genes for carotid plaque in Dominicans.
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DOI：
10.1016/j.atherosclerosis.2012.03.025
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发表时间：
2012-07
期刊：
影响因子：
5.3
通讯作者：
Sacco, Ralph L.
中科院分区：
文献类型：
--
作者：
Dong, Chuanhui;Beecham, Ashley;Wang, Liyong;Blanton, Susan H.;Rundek, Tatjana;Sacco, Ralph L.
颈动脉斑块是亚临床动脉粥样硬化的标志，具有遗传成分。这项后续精细定位研究的目的是确定四个连锁区域内颈动脉斑块的候选基因。我们成功地对先前在100个多米尼加大家庭中发现的四个连锁区域下的3712个单核苷酸多态(SNPs)进行了基因分型。以家庭为基础的关联性测试被用来调查它们与颈动脉斑块的相关性。来自曼哈顿北部研究(NOMAS)的一个独立的基于人群的亚队列(N=941,384名多米尼加人)对有希望的SNPs进行了评估。在家族研究中，发现了几个基因(NAV2、EFCAB11/TDP1、AGBL1、PTPN9、LING01和LOC730118)存在关联的证据(p<；0.0005)，其中EFCAB11/Tdp1附近的rs4143999关联最强(颈动脉存在的p=0.00001，斑块面积的p=0.00003，多次检测校正了p≤0.02)。AGBL1和PTPN9的关联主要由有连锁证据的家系驱动(在有连锁证据的家系中p=0.00008~0.00001，在没有连锁证据的家系中p=0.76~0.32)。然而，这些关联只解释了观察到的联系的一小部分。在NOMAS中，在EFCAB11、NAV2、AGBL1和其他基因内/附近发现了SNP的复制(在整个NOMAS亚队列中p<；0.05，在较小的多米尼加亚队列中p<；0.10)。这项后续研究在多米尼加人群中确定了颈动脉斑块的多个候选基因。这些基因中的许多都与神经退行性疾病和心血管疾病有关。需要进行深入的重新测序的进一步研究，以发现导致动脉粥样硬化易感性的罕见和常见的功能变异。
Carotid plaque is a marker of subclinical atherosclerosis with a genetic component. The aim of this follow-up fine mapping study was to identify candidate genes for carotid plaque within four linkage regions. We successfully genotyped 3,712 single nucleotide polymorphisms (SNPs) under the four linkage regions that were previously identified in 100 extended Dominican families. Family-based association tests were performed to investigate their associations with carotid plaque. Promising SNPs were evaluated in an independent population-based subcohort (N=941, 384 Dominicans) from the Northern Manhattan Study (NOMAS). In the family study, evidence for association (p<0.0005) was found regarding several genes (NAV2, EFCAB11/TDP1, AGBL1, PTPN9, LINGO1 and LOC730118), with the strongest association at rs4143999 near EFCAB11/TDP1 (p=0.00001 for carotid presence and 0.00003 for plaque area, multiple testing corrected p≤0.02). The association in AGBL1 and PTPN9 was mainly driven by the families with linkage evidence (p=0.00008~0.00001 and 0.76~0.32, respectively, in the families with and without linkage evidence). However, these associations explained only a small portion of the observed linkage. In NOMAS, replication (p<0.05 in the whole NOMAS subcohort and p<0.10 in the smaller Dominican subcohort) was found for SNPs within/near EFCAB11, NAV2, AGBL1 and other genes. This follow-up study has identified multiple candidate genes for carotid plaque in the Dominican population. Many of these genes have been implicated in neurodegenerative and cardiovascular diseases. Further studies with in-depth re-sequencing are needed to uncover both rare and common functional variants that contribute to the susceptibility to atherosclerosis.
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影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
DOI：
10.1161/circgenetics.109.895995
发表时间：
2010-06
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Morrison AC;Felix JF;Cupples LA;Glazer NL;Loehr LR;Dehghan A;Demissie S;Bis JC;Rosamond WD;Aulchenko YS;Wang YA;Haritunians T;Folsom AR;Rivadeneira F;Benjamin EJ;Lumley T;Couper D;Stricker BH;O'Donnell CJ;Rice KM;Chang PP;Hofman A;Levy D;Rotter JI;Fox ER;Uitterlinden AG;Wang TJ;Psaty BM;Willerson JT;van Duijn CM;Boerwinkle E;Witteman JC;Vasan RS;Smith NL
通讯作者：
Smith NL
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
11.4
作者：
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通讯作者：
Pommier, Yves
影响因子：
9.8
作者：
Abecasis, GR;Cardon, LR;Cookson, WOC
通讯作者：
Cookson, WOC