Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations
Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations
复制标题
全基因组荟萃分析确定了与中国和欧洲血统人群中 n-3 和 n-6 多不饱和脂肪酸水平相关的新位点
DOI：
10.1093/hmg/ddw002
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发表时间：
2016-03-15
影响因子：
3.5
通讯作者：
Lin, Xu
中科院分区：
文献类型：
--
作者：
Hu, Yao;Li, Huaixing;Lin, Xu
流行病学研究表明，n-3和n-6长链多不饱和脂肪酸水平与不同种族人群的心脏代谢结果风险相关。最近在欧洲血统人群中的全基因组关联研究已经确定了与血浆和/或红细胞多不饱和脂肪酸相关的几个位点。为了确定其他新的基因座，我们在两个基于人群的队列中进行了全基因组关联研究，包括3521名中国参与者，然后对8962名欧洲血统参与者的荟萃分析结果进行了跨种族荟萃分析。在跨种族荟萃分析中，4个新基因座（MYB、AGPAT 4、DGAT 2和PPT 2）达到全基因组显著性（log 10（贝叶斯因子）>= 6）。其中，MYB和AGPAT 4与二十二碳四烯酸（log 10（贝叶斯因子）分别为11.5和8.69）在中国特有的全基因组关联分析中也达到了全基因组显著性（P = 4.15 x 10（-14）和4.30 x 10（-12）），而DGAT 2与γ-亚麻酸的结合（log 10（贝叶斯因子）= 6.16）和PPT 2与二十二碳五烯酸的关系（log 10（贝叶斯因子）= 6.24）在中国和欧洲特异性全基因组关联分析中均具有名义显著性（P = 0.003）。我们还证实了以前报道的基因座包括FADS 1，NTAN 1，NRBF 2，NRFVL 2和GCKR。在FADS 1中观察到不同的效应大小，在FADS VL 2中观察到独立的关联信号。这些结果为了解多不饱和脂肪酸的遗传背景及其在中国和欧洲人群中的差异提供了新的见解。
Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) >= 6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P = 4.15 x 10(-14) and 4.30 x 10(-12), respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P = 0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR. Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations.