Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study.
Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study.
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DOI：
10.1161/circgenetics.111.960096
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发表时间：
2011-12
期刊：
影响因子：
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通讯作者：
Heiss G
中科院分区：
文献类型：
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作者：
Franceschini N;Carty C;Bůzková P;Reiner AP;Garrett T;Lin Y;Vöckler JS;Hindorff LA;Cole SA;Boerwinkle E;Lin DY;Bookman E;Best LG;Bella JN;Eaton C;Greenland P;Jenny N;North KE;Taverna D;Young AM;Deelman E;Kooperberg C;Psaty B;Heiss G
全基因组关联研究发现了几种与冠心病（CHD）相关的单核苷酸多态性（SNP），但与CHD事件的关联却知之甚少。在美国4个大型前瞻性队列的5个祖先组中检查了13个已发表的CHD SNP的相关性。分析包括多达26，617名白色个体（6，626起事件）、8，018名非洲裔美国人（914起事件）、1，903名西班牙裔美国人（113起事件）、3，669名美洲印第安人（595起事件）和885名亚洲/太平洋岛民（66起事件）的平均随访时间内的冠状动脉事件。我们使用了考克斯比例风险模型（加性遗传模式），根据年龄、性别和血统（根据需要）进行了调整。9个位点与白人CHD事件的发生有统计学相关性：9p21（rs10757278，p=4.7 × 10−41），16q23.1（rs2549513，p=0.0004），6p24.1（rs499818，p=0.0002），2q36.3（rs2943634，p=6.7 × 10−6），MTHFDIL（rs6922269，p=5.1 × 10−10）、APOE（rs429358，p=2.7 × 10−18）、ZNF 627（rs4804611，p=5.0 × 10−8）、CXCL 12（rs501120，p=1.4 × 10−6）和LPL（rs268，p=2.7 × 10−17）。9 p21区域显示出显著的研究间异质性，在55岁或更年轻的个体和女性中具有更大的影响。在CHD事件中纳入冠状动脉血运重建术引入了异质性。SNPs与非裔美国人的CHD无关，并且在其他美国少数民族中存在不同的关联。对白色个体的前瞻性分析重复了几个已报道的横截面CHD-SNP关联。
Genome wide association studies identified several single nucleotide polymorphisms (SNPs) associated with prevalent coronary heart disease (CHD) but less is known of associations with incident CHD. The association of thirteen published CHD SNPs was examined in five ancestry groups of four large US prospective cohorts. The analyses included incident coronary events over 9.1 to 15.7 average follow-up times in up to 26,617 white individuals (6,626 events), 8,018 African Americans (914 events), 1,903 Hispanics (113 events), 3,669 American Indians (595 events) and 885 Asian/Pacific Islanders (66 events). We used Cox proportional hazards models (with additive mode of inheritance) adjusted for age, sex and ancestry (as needed). Nine loci were statistically associated with incident CHD events in whites: 9p21 (rs10757278, p=4.7 × 10−41), 16q23.1 (rs2549513, p=0.0004), 6p24.1 (rs499818, p=0.0002), 2q36.3 (rs2943634, p=6.7 × 10−6), MTHFDIL (rs6922269, p=5.1 × 10−10), APOE (rs429358, p=2.7 × 10−18), ZNF627 (rs4804611, p=5.0 × 10−8), CXCL12 (rs501120, p=1.4 × 10−6) and LPL (rs268, p=2.7 × 10−17). The 9p21 region showed significant between-study heterogeneity, with larger effects in individuals aged 55 years or younger and in women. Inclusion of coronary revascularization procedures among the incident CHD events introduced heterogeneity. The SNPs were not associated with CHD in African Americans and associations varied in other US minorities. Prospective analyses of white individuals replicated several reported cross-sectional CHD-SNP associations.