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基因座。
Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations.
作者信息
Hu Yao, Li Huaixing, Lu Ling, Manichaikul Ani, Zhu Jingwen, Chen Yii-Der I, Sun Liang, Liang Shuang, Siscovick David S, Steffen Lyn M, Tsai Michael Y, Rich Stephen S, Lemaitre Rozenn N, Lin Xu
机构信息
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
Center for Public Health Genomics and Department of Public Health Sciences, Biostatistics Section, University of Virginia, Charlottesville, VA, USA.
出版信息
Hum Mol Genet. 2016 Mar 15;25(6):1215-24. doi: 10.1093/hmg/ddw002. Epub 2016 Jan 6.
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 × 10(-14) and 4.30 × 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.
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血管代谢结局风险相关。最近在欧洲血统人群中进行的全基因组关联研究已经确定了几个与血浆和/或红细胞多不饱和脂肪酸相关的基因座。为了识别其他新的基因座,我们在两个基于人群的队列中进行了全基因组关联研究,这两个队列由3521名中国参与者组成,随后与来自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。四个新的基因座(MYB、AGPAT4、DGAT2和PPT2)在跨种族荟萃分析中达到全基因组显著性水平(对数10贝叶斯因子≥6)。其中,MYB和AGPAT4与二十二碳四烯酸的关联(对数10贝叶斯因子分别为11.5和8.69)在中国特异性全基因组关联分析中也达到了全基因组显著性水平(P分别为4.15×10⁻¹⁴和4.30×10⁻¹²),而DGAT2与γ-亚麻酸的关联(对数10贝叶斯因子=6.16)以及PPT2与二十二碳五烯酸的关联(对数10贝叶斯因子=6.24)在中国人和欧洲人特异性全基因组关联分析中均具有名义显著性(P≤0.003)。我们还证实了先前报道的基因座,包括FADS1、NTAN1、NRBF2、ELOVL2和GCKR。观察到FADS1中不同的效应大小和ELOVL2中的独立关联信号。这些结果为多不饱和脂肪酸的遗传背景及其在中国和欧洲人群之间的差异提供了新的见解。