Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs.
Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs.
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DOI：
10.1038/srep19429
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发表时间：
2016-01-19
影响因子：
4.6
通讯作者：
Valladares-Salgado A
中科院分区：
文献类型：
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作者：
Below JE;Parra EJ;Gamazon ER;Torres J;Krithika S;Candille S;Lu Y;Manichakul A;Peralta-Romero J;Duan Q;Li Y;Morris AP;Gottesman O;Bottinger E;Wang XQ;Taylor KD;Ida Chen YD;Rotter JI;Rich SS;Loos RJ;Tang H;Cox NJ;Cruz M;Hanis CL;Valladares-Salgado A
我们对墨西哥和墨西哥裔美国人血统的三个样本（包括4，383人）进行了脂质性状的全基因组荟萃分析，并在另外三个西班牙裔样本（包括7，876人）中进行了显著和高度暗示性的关联。在CELSR 2、ZNF 259/APOA 5、KANK 2/DOCK 6和NCAN/MAU 2中或附近观察到总胆固醇的全基因组显著信号，在LPL、ABCA 1、ZNF 259/APOA 5、LIPC和CETP中观察到HDL胆固醇的全基因组显著信号，在CELSR 2、APOB和NCAN/MAU 2中观察到LDL胆固醇的全基因组显著信号，在GCKR、TRIB 1、ZNF 259/APOA 5和NCAN/MAU 2中观察到甘油三酯的全基因组显著信号。连锁不平衡和条件分析表明，在ABCA 1和LIPC观察到的信号HDL胆固醇和NCAN/MAU 2甘油三酯是独立的先前报道的铅SNP协会。在我们的西班牙裔样本中对欧洲全球脂质遗传学联盟（GLGC）数据集的主要SNP进行的分析显示，效应方向显着一致，并且效应大小具有强相关性。对欧洲GLGC和我们的西班牙裔数据集的荟萃分析确定了五个达到全基因组意义的新区域：两个总胆固醇（FN 1和SAMM 50），两个HDL胆固醇（LOC 100996634和COPB 1）和一个LDL胆固醇（LINC 00324/CTC 1/PFAS）。发现最高荟萃分析信号以组织特异性方式富集与基因表达相关的SNP，表明脂质相关基因座中组织特异性功能的富集。
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.