Genetic variants influencing circulating lipid levels and risk of coronary artery disease.
Genetic variants influencing circulating lipid levels and risk of coronary artery disease.
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DOI：
10.1161/atvbaha.109.201020
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发表时间：
2010-11
期刊：
影响因子：
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通讯作者：
Sandhu MS
中科院分区：
文献类型：
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作者：
Waterworth DM;Ricketts SL;Song K;Chen L;Zhao JH;Ripatti S;Aulchenko YS;Zhang W;Yuan X;Lim N;Luan J;Ashford S;Wheeler E;Young EH;Hadley D;Thompson JR;Braund PS;Johnson T;Struchalin M;Surakka I;Luben R;Khaw KT;Rodwell SA;Loos RJ;Boekholdt SM;Inouye M;Deloukas P;Elliott P;Schlessinger D;Sanna S;Scuteri A;Jackson A;Mohlke KL;Tuomilehto J;Roberts R;Stewart A;Kesäniemi YA;Mahley RW;Grundy SM;Wellcome Trust Case Control Consortium;McArdle W;Cardon L;Waeber G;Vollenweider P;Chambers JC;Boehnke M;Abecasis GR;Salomaa V;Järvelin MR;Ruokonen A;Barroso I;Epstein SE;Hakonarson HH;Rader DJ;Reilly MP;Witteman JC;Hall AS;Samani NJ;Strachan DP;Barter P;van Duijn CM;Kooner JS;Peltonen L;Wareham NJ;McPherson R;Mooser V;Sandhu MS
遗传学研究可能为脂质代谢和CAD风险的生物学机制提供新的见解。因此，我们进行了一项全基因组关联研究，以确定LDL-c、HDL-c和甘油三酯的新遗传决定因素。我们结合了来自8项研究的全基因组关联数据，包括多达17，723名参与者的循环脂质浓度信息。我们对来自8个人群的多达37，774名参与者进行了独立的重复研究，并在印度亚裔人群中进行了研究。我们还评估了多达9，633例病例和38，684例对照中脂质位点的SNP与CAD风险之间的关联。我们发现了4个新的基因位点，它们与脂质具有可重复的关联（P值为1.6 × 10−8至3.1 × 10−10）。这些包括SLC 39 A8基因中的HDL-c的潜在功能SNP，LDL-c的MYLIP/GMPR和PPP 1 R3 B基因附近的SNP以及甘油三酯的AFF 1基因。在CELSR 2、APOB、APOE-C1-C4-C2簇、LPL、ZNF 259-APOA 5-A4-C3-A1簇和TRIB 1位点显示与一个或多个脂质性状具有强统计学关联的SNP也与CAD风险相关（P值1.1 × 10−3至1.2 × 10−9）。我们已经确定了四个新的基因座与循环脂质。我们还表明，除了与LDL-c主要相关的基因座外，主要与循环甘油三酯和HDL-c相关的基因座也与CAD风险相关。这些发现可能为脂质代谢和CAD风险的生物学机制提供新的见解。
Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of LDL-c, HDL-c and triglycerides. We combined genome-wide association data from eight studies, comprising up to 17,723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37,774 participants from eight populations and also in a population of Indian Asian descent. We also assessed the association between SNPs at lipid loci and risk of CAD in up to 9,633 cases and 38,684 controls. We identified four novel genetic loci that showed reproducible associations with lipids (P values 1.6 × 10−8 to 3.1 × 10−10). These include a potentially functional SNP in the SLC39A8 gene for HDL-c, a SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-c and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with one or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (P values 1.1 × 10−3 to 1.2 × 10−9). We have identified four novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-c, genetic loci mainly associated with circulating triglycerides and HDL-c are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.