Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.
Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.
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DOI：
10.1371/journal.pone.0050198
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Keating BJ
中科院分区：
文献类型：
--
作者：
Elbers CC;Guo Y;Tragante V;van Iperen EP;Lanktree MB;Castillo BA;Chen F;Yanek LR;Wojczynski MK;Li YR;Ferwerda B;Ballantyne CM;Buxbaum SG;Chen YD;Chen WM;Cupples LA;Cushman M;Duan Y;Duggan D;Evans MK;Fernandes JK;Fornage M;Garcia M;Garvey WT;Glazer N;Gomez F;Harris TB;Halder I;Howard VJ;Keller MF;Kamboh MI;Kooperberg C;Kritchevsky SB;LaCroix A;Liu K;Liu Y;Musunuru K;Newman AB;Onland-Moret NC;Ordovas J;Peter I;Post W;Redline S;Reis SE;Saxena R;Schreiner PJ;Volcik KA;Wang X;Yusuf S;Zonderland AB;Anand SS;Becker DM;Psaty B;Rader DJ;Reiner AP;Rich SS;Rotter JI;Sale MM;Tsai MY;Borecki IB;Hegele RA;Kathiresan S;Nalls MA;Taylor HA Jr;Hakonarson H;Sivapalaratnam S;Asselbergs FW;Drenos F;Wilson JG;Keating BJ
对欧洲人群的荟萃分析已经成功地确定了与脂质水平相关的100多个位点的遗传变异，但我们对其他种族的了解仍然有限。为了解决这个问题，我们使用IBC阵列（一种定制的~ 50,000 SNP基因分型阵列）对7,657名非洲裔美国人、1,315名西班牙裔美国人和841名东亚人的约2,000个候选基因进行了密集的基因分型。荟萃分析证实了先前在欧洲人群中建立的16个脂质位点具有全基因组显著性水平，并在这些脂质位点中发现了多个独立的关联信号。在7,000个非裔美国人样本的初步发现和计算机随访中，证实了两个新的基因座：ICAM1中的rs5030359与总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）相关（p = 8.8×10−7和p = 1.5×10−6分别），CD36中的无意义突变rs3211938与高密度脂蛋白胆固醇（HDL-C）水平相关（p = 13.5×10−12）。rs3211938-G等位基因，在欧洲和亚洲人群中几乎不存在，之前已经发现与CD36缺乏症有关，并且在非洲人和非裔美国人中显示出选择的特征。最后，我们评估了在欧洲人群中建立的snp对多种族人群中脂质水平的影响，并表明大多数已知的脂质相关信号跨越了种族。然而，人群之间的差异，特别是等位基因频率的差异，可以用来识别新的信号，正如在本报告中发现的ICAM1和CD36所示。
Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10−7 and p = 1.5×10−6 respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10−12). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.
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作者：
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通讯作者：
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