Below Jennifer E, Parra Esteban J, Gamazon Eric R, Torres Jason, Krithika S, Candille Sophie, Lu Yingchang, Manichakul Ani, Peralta-Romero Jesus, Duan Qing, Li Yun, Morris Andrew P, Gottesman Omri, Bottinger Erwin, Wang Xin-Qun, Taylor Kent D, Ida Chen Y-D, Rotter Jerome I, Rich Stephen S, Loos Ruth J F, Tang Hua, Cox Nancy J, Cruz Miguel, Hanis Craig L, Valladares-Salgado Adan
Division of epidemiology, Human Genetics &Environmental Sciences, University of Texas School of Public Health, Houston, Texas, USA.
Department of Anthropology, University of Toronto at Mississauga, Mississauga, Ontario, Canada.
Sci Rep. 2016 Jan 19;6:19429. doi: 10.1038/srep19429.
We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci.
我们对三个具有墨西哥和墨西哥裔美国人血统的样本（共4383人）进行了脂质性状的全基因组荟萃分析，并在另外三个包含7876人的西班牙裔样本中对显著和高度提示性的关联进行了跟进。在CELSR2、ZNF259/APOA5、KANK2/DOCK6和NCAN/MAU2附近观察到全基因组显著信号，涉及总胆固醇；在LPL、ABCA1、ZNF259/APOA5、LIPC和CETP附近观察到全基因组显著信号，涉及高密度脂蛋白胆固醇；在CELSR2、APOB和NCAN/MAU2附近观察到全基因组显著信号，涉及低密度脂蛋白胆固醇；在GCKR、TRIB1、ZNF259/APOA5和NCAN/MAU2附近观察到全基因组显著信号，涉及甘油三酯。连锁不平衡和条件分析表明，在ABCA1和LIPC处观察到的高密度脂蛋白胆固醇信号以及在NCAN/MAU2处观察到的甘油三酯信号独立于先前报道的主要单核苷酸多态性（SNP）关联。在我们的西班牙裔样本中对来自欧洲全球脂质遗传学联盟（GLGC）数据集的主要SNP进行分析，结果显示效应方向具有显著一致性，效应大小也具有很强的相关性。对欧洲GLGC数据集和我们的西班牙裔数据集进行的荟萃分析确定了五个达到全基因组显著性的新区域：两个与总胆固醇相关（FN1和SAMM50），两个与高密度脂蛋白胆固醇相关（LOC100996634和COPB1），一个与低密度脂蛋白胆固醇相关（LINC00324/CTC1/PFAS）。发现荟萃分析的顶级信号以组织特异性方式富集了与基因表达相关的SNP，这表明脂质相关基因座中存在组织特异性功能的富集。
