Below_et_al_2016.pdf (606.21 kB)
Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects and tissue-specific enrichment of eQTLs
journal contribution
posted on 2023-07-26, 15:04 authored by Jennifer E. Below, Esteban J. Parra, Eric R. Gamazon, Jason Torres, S. Krithika, Sophie Candille, Yingchang Lu, Ani Manichakul, Jesus Peralta-Romero, Qing Duan, Yun Li, Andrew P. Morris, Omri Gottesman, Erwin Bottinger, Xin-Qun Wang, Kent D. Taylor, Y.-D. Ida Chen, Jerome I. Rotter, Stephen S. Rich, Ruth J. F. Loos, Hua Tang, Nancy J. Cox, Miguel Cruz, Craig L. Hanis, Adan Valladares-SalgadoWe 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.
History
Refereed
- Yes
Volume
6Issue number
1Page range
19429Publication title
Scientific ReportsISSN
2045-2322External DOI
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Nature ResearchFile version
- Published version
Language
- eng
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2020-07-30Legacy creation date
2020-07-30Legacy Faculty/School/Department
ARCHIVED Faculty of Science & Technology (until September 2018)Usage metrics
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