Newly identified loci that influence lipid concentrations and risk of coronary artery disease
Newly identified loci that influence lipid concentrations and risk of coronary artery disease
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DOI：
10.1038/ng.76
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发表时间：
2008-02-01
期刊：
影响因子：
30.8
通讯作者：
Abecasis, Goncalo R.
中科院分区：
文献类型：
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作者：
Willer, Cristen J.;Sanna, Serena;Abecasis, Goncalo R.
为了确定影响血脂浓度的遗传变异，我们首先使用基因型插补和荟萃分析来结合联合收割机三个全基因组扫描，总共8，816个个体，包括我们研究的6，068个个体（1，874例来自2型糖尿病的FUSION研究，4，184例来自SardiNIA研究的衰老相关变量）和2，来自糖尿病遗传学倡议的758名个体，在本期的一项伴随研究中报道。随后，我们在另外11，569名个体中检查了有希望的信号。总的来说，我们确定了11个先前与脂质代谢有关的基因座的强相关变体（ABCA 1、APOA 5-APOA 4-APOC 3-APOA 1和APOE-APOC簇、APOB、CETP、GCKR、LDLR、LPL、LIPC、LIPG和PCSK 9）以及几个新鉴定的基因座（接近MVK-MMAB和GALNT 2，具有主要与高密度脂蛋白（HDL）胆固醇相关的变体;在SORT 1附近，具有主要与低密度脂蛋白（LDL）胆固醇相关的变体;在TRIB 1、MLXIPL和ANGPTL 3附近，具有主要与甘油三酯相关的变体;以及在NCAN附近包含几个基因的基因座，具有与甘油三酯和LDL胆固醇两者强烈相关的变体）。值得注意的是，在我们的研究中，与LDL胆固醇浓度增加相关的11个独立变异体在冠状动脉疾病病例样本中的频率也高于对照组。
To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.