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Meta-Analysis
. 2016 Jan 19:6:19429.
doi: 10.1038/srep19429.

Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs

Jennifer E Below  1 , Esteban J Parra  2 , Eric R Gamazon  3   4   5 , Jason Torres  3 , S Krithika  2 , Sophie Candille  6 , Yingchang Lu  7   8 , Ani Manichakul  9 , Jesus Peralta-Romero  10 , Qing Duan  11 , Yun Li  11 , Andrew P Morris  12 , Omri Gottesman  7 , Erwin Bottinger  7 , Xin-Qun Wang  13 , Kent D Taylor  14 , Y-D Ida Chen  14 , Jerome I Rotter  14 , Stephen S Rich  9 , Ruth J F Loos  7   8 , Hua Tang  6 , Nancy J Cox  3   4 , Miguel Cruz  10 , Craig L Hanis  1 , Adan Valladares-Salgado  10
Affiliations
Meta-Analysis

Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs

Jennifer E Below et al. Sci Rep. .

Abstract

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.

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