Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans.
Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans.
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DOI：
10.1007/s00439-014-1439-z
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发表时间：
2014-08
期刊：
影响因子：
5.3
通讯作者：
Lange, Leslie A.
中科院分区：
文献类型：
--
作者：
Ellis, Jaclyn;Lange, Ethan M.;Li, Jin;Dupuis, Josee;Baumert, Jens;Walston, Jeremy D.;Keating, Brendan J.;Durda, Peter;Fox, Ervin R.;Palmer, Cameron D.;Meng, Yan A.;Young, Taylor;Farlow, Deborah N.;Schnabel, Renate B.;Marzi, Carola S.;Larkin, Emma;Martin, Lisa W.;Bis, Joshua C.;Auer, Paul;Ramachandran, Vasan S.;Gabriel, Stacey B.;Willis, Monte S.;Pankow, James S.;Papanicolaou, George J.;Rotter, Jerome I.;Ballantyne, Christie M.;Gross, Myron D.;Lettre, Guillaume;Wilson, James G.;Peters, Ulrike;Koenig, Wolfgang;Tracy, Russell P.;Redline, Susan;Reiner, Alex P.;Benjamin, Emelia J.;Lange, Leslie A.
C-反应蛋白（CRP）是全身性炎症的遗传生物标志物，也是心血管疾病（CVD）的预测因子。CRP的大规模遗传关联研究主要集中在欧洲血统的个体。我们试图使用ITMAT Broad-CARe（IBC）阵列在多种族样本中发现CRP的新遗传变异，ITMAT Broad-CARe（IBC）阵列是一种定制的50，000 SNP基因中心阵列，密集覆盖了2，000多个候选CVD基因。我们对来自候选基因关联资源（CARe）研究的7570名非洲裔美国人（AA）进行了分析，并进行了种族合并荟萃分析，其中包括来自CARe，妇女健康倡议（WHI）和KORA研究的29，939名欧洲血统的额外个体。我们观察到AA中四个基因座的全阵列显著性（p<2.2×10−6），其中三个基因座先前在欧洲血统个体中报道过（IL 6 R，p=2.0×10−6; CRP，p=4.2×10−71; APOE，p=1.6×10−6）。第四个显著的基因座是CD 36（p=1.6×10−6），它位于一个功能变异体（rs3211938）上，这在欧洲血统的个体中极为罕见。我们在来自WHI的8041名AA女性的独立样本中复制了CD 36结果（p=1.8×10−5）;结合CARe和WHI AA结果的rs3211938荟萃分析达到了全基因组显著性（p=1.5×10−10）。在种族合并荟萃分析中，13个位点达到显著性，包括10个（CRP、TOMM 40/APOE/APOC 1、HNF 1A、LEPR、GCKR、IL 6 R、IL 1 RN、NLRP 3、HNF 4A和BAZ 1B/BCL 7 B）先前与CRP相关，1个（ARNTL）先前报告与CRP名义上相关。还检测到两个新的基因座（RPS 6 KB 1，p=2.0×10−6; CD 36，p=1.4×10−6）。这些结果强调了与欧洲血统人群相比，AA中CRP的共同和独特遗传风险因素。
C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Large-scale genetic association studies for CRP have largely focused on individuals of European descent. We sought to uncover novel genetic variants for CRP in a multi-ethnic sample using the ITMAT Broad-CARe (IBC) array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate CVD genes. We performed analyses on 7570 African Americans (AA) from the Candidate gene Association Resource (CARe) study and race-combined meta-analyses that included 29,939 additional individuals of European descent from CARe, the Women’s Health Initiative (WHI) and KORA studies. We observed array-wide significance (p<2.2×10−6) for four loci in AA, three of which have been reported previously in individuals of European descent (IL6R, p=2.0×10−6; CRP, p=4.2×10−71; APOE, p=1.6×10−6). The fourth significant locus, CD36 (p=1.6×10−6), was observed at a functional variant (rs3211938) that is extremely rare in individuals of European descent. We replicated the CD36 finding (p=1.8×10−5) in an independent sample of 8041 AA women from WHI; a meta-analysis combining the CARe and WHI AA results at rs3211938 reached genome-wide significance (p=1.5×10−10). In the race-combined meta-analyses, 13 loci reached significance, including ten (CRP, TOMM40/APOE/APOC1, HNF1A, LEPR, GCKR, IL6R, IL1RN, NLRP3, HNF4A and BAZ1B/BCL7B) previously associated with CRP, and one (ARNTL) previously reported to be nominally associated with CRP. Two novel loci were also detected (RPS6KB1, p=2.0×10−6; CD36, p=1.4×10−6). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent.
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影响因子：
37.8
作者：
Dehghan A;Dupuis J;Barbalic M;Bis JC;Eiriksdottir G;Lu C;Pellikka N;Wallaschofski H;Kettunen J;Henneman P;Baumert J;Strachan DP;Fuchsberger C;Vitart V;Wilson JF;Paré G;Naitza S;Rudock ME;Surakka I;de Geus EJ;Alizadeh BZ;Guralnik J;Shuldiner A;Tanaka T;Zee RY;Schnabel RB;Nambi V;Kavousi M;Ripatti S;Nauck M;Smith NL;Smith AV;Sundvall J;Scheet P;Liu Y;Ruokonen A;Rose LM;Larson MG;Hoogeveen RC;Freimer NB;Teumer A;Tracy RP;Launer LJ;Buring JE;Yamamoto JF;Folsom AR;Sijbrands EJ;Pankow J;Elliott P;Keaney JF;Sun W;Sarin AP;Fontes JD;Badola S;Astor BC;Hofman A;Pouta A;Werdan K;Greiser KH;Kuss O;Meyer zu Schwabedissen HE;Thiery J;Jamshidi Y;Nolte IM;Soranzo N;Spector TD;Völzke H;Parker AN;Aspelund T;Bates D;Young L;Tsui K;Siscovick DS;Guo X;Rotter JI;Uda M;Schlessinger D;Rudan I;Hicks AA;Penninx BW;Thorand B;Gieger C;Coresh J;Willemsen G;Harris TB;Uitterlinden AG;Järvelin MR;Rice K;Radke D;Salomaa V;Willems van Dijk K;Boerwinkle E;Vasan RS;Ferrucci L;Gibson QD;Bandinelli S;Snieder H;Boomsma DI;Xiao X;Campbell H;Hayward C;Pramstaller PP;van Duijn CM;Peltonen L;Psaty BM;Gudnason V;Ridker PM;Homuth G;Koenig W;Ballantyne CM;Witteman JC;Benjamin EJ;Perola M;Chasman DI
通讯作者：
Chasman DI
影响因子：
9.8
作者：
Auer, Paul L.;Johnsen, Jill M.;Li, Yun
通讯作者：
Li, Yun
影响因子：
5.8
作者：
Anderson, Carl A.;Zhu, Gu;Montgomery, Grant W.
通讯作者：
Montgomery, Grant W.
影响因子：
5.9
作者：
Harris, TB;Ferrucci, L;Wallace, R
通讯作者：
Wallace, R
影响因子：
2.1
作者：
Li, Yun;Willer, Cristen J.;Ding, Jun;Scheet, Paul;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.