Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs
Autor: | Ruth J. F. Loos, Ani W. Manichakul, Eric R. Gamazon, Kent D. Taylor, Craig L. Hanis, Esteban J. Parra, Adan Valladares-Salgado, Jerome I. Rotter, Hua Tang, Sophie I. Candille, Xin-Qun Wang, Miguel Cruz, Erwin P. Bottinger, Nancy J. Cox, Qing Duan, S. Krithika, Jesús Peralta-Romero, Yingchang Lu, Jason M. Torres, Jennifer E. Below, Andrew P. Morris, Stephen S. Rich, Yun Li, Omri Gottesman, Y.-D. Ida Chen |
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Přispěvatelé: | Other departments, Amsterdam Neuroscience - Complex Trait Genetics |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Linkage disequilibrium Apolipoprotein B Genotype Population Quantitative Trait Loci Genome-wide association study Single-nucleotide polymorphism Quantitative trait locus Polymorphism Single Nucleotide Article Linkage Disequilibrium White People 03 medical and health sciences chemistry.chemical_compound Quantitative Trait 0302 clinical medicine Quantitative Trait Heritable Genetics Humans Polymorphism education Heritable Mexico Genetic Association Studies education.field_of_study Multidisciplinary biology Cholesterol Human Genome Single Nucleotide Hispanic or Latino Atherosclerosis Lipid Metabolism Lipids 030104 developmental biology Genetics Population chemistry Organ Specificity ABCA1 biology.protein lipids (amino acids peptides and proteins) 030217 neurology & neurosurgery Genome-Wide Association Study |
Zdroj: | Scientific Reports Scientific reports, vol 6, iss 1 Scientific reports, 6. Nature Publishing Group |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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