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Trans-ancestry Fine Mapping and Molecular Assays Identify Regulatory Variants at the ANGPTL8 HDL-C GWAS Locus.
- Source :
-
G3: Genes | Genomes | Genetics . Sep2017, Vol. 7 Issue 9, p3217-3227. 11p. - Publication Year :
- 2017
-
Abstract
- Recent genome-wide association studies (GWAS) have identified variants associated with highdensity lipoprotein cholesterol (HDL-C) located in or near the ANGPTL8 gene. Given the extensive sharing of GWAS loci across populations, we hypothesized that at least one shared variant at this locus affects HDL-C. The HDL-C-associated variants are coincident with expression quantitative trait loci for ANGPTL8 and DOCK6 in subcutaneous adipose tissue; however, only ANGPTL8 expression levels are associated with HDL-C levels. We identified a 400-bp promoter region of ANGPTL8 and enhancer regions within 5 kb that contribute to regulating expression in liver and adipose. To identify variants functionally responsible for the HDL-C association, we performed fine-mapping analyses and selected 13 candidate variants that overlap putative regulatory regions to test for allelic differences in regulatory function. Of these variants, rs12463177-G increased transcriptional activity (1.5-fold, P = 0.004) and showed differential protein binding. Six additional variants (rs17699089, rs200788077, rs56322906, rs3760782, rs737337, and rs3745683) showed evidence of allelic differences in transcriptional activity and/or protein binding. Taken together, these data suggest a regulatory mechanism at the ANGPTL8 HDL-C GWAS locus involving tissue-selective expression and at least one functional variant. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HIGH density lipoproteins
*CHOLESTEROL
*GENE expression
Subjects
Details
- Language :
- English
- ISSN :
- 21601836
- Volume :
- 7
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- G3: Genes | Genomes | Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 125345957
- Full Text :
- https://doi.org/10.1534/g3.117.300088