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

Below, Jennifer E. and Parra, Esteban J. and Gamazon, Eric R. and Torres, Jason and Krithika, S. and Candille, Sophie and Lu, Yingchang and Manichakul, Ani and Peralta-Romero, Jesus and Duan, Qing and Li, Yun and Morris, Andrew P. and Gottesman, Omri and Bottinger, Erwin and Wang, Xin-Qun and Taylor, Kent D. and Ida Chen, Y.-D. and Rotter, Jerome I. and Rich, Stephen S. and Loos, Ruth J. F. and Tang, Hua and Cox, Nancy J. and Cruz, Miguel and Hanis, Craig L. and Valladares-Salgado, Adan (2016) Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects and tissue-specific enrichment of eQTLs. Scientific Reports, 6 (1). p. 19429. ISSN 2045-2322

[img] Text
Published Version
Available under the following license: Creative Commons Attribution.

Download (620kB)
Official URL: https://doi.org/10.1038/srep19429

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.

Item Type: Journal Article
Keywords: Gene expression, Genome-wide association studies, Quantitative trait loci, Risk factors
Faculty: ARCHIVED Faculty of Science & Technology (until September 2018)
Depositing User: Lisa Blanshard
Date Deposited: 30 Jul 2020 13:13
Last Modified: 09 Sep 2021 19:00
URI: https://arro.anglia.ac.uk/id/eprint/705732

Actions (login required)

Edit Item Edit Item