Title | Genetic variants in microRNA genes and targets associated with cardiovascular disease risk factors in the African-American population. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Li, C, Grove, ML, Yu, B, Jones, BC, Morrison, A, Boerwinkle, E, Liu, X |
Journal | Hum Genet |
Volume | 137 |
Issue | 1 |
Pagination | 85-94 |
Date Published | 2018 Jan |
ISSN | 1432-1203 |
Keywords | 3' Untranslated Regions, Adult, Black or African American, Cardiovascular Diseases, Female, Genetic Predisposition to Disease, Genotyping Techniques, Humans, Male, MicroRNAs, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Whole Genome Sequencing |
Abstract | The purpose of this study is to identify microRNA (miRNA) related polymorphism, including single nucleotide variants (SNVs) in mature miRNA-encoding sequences or in miRNA-target sites, and their association with cardiovascular disease (CVD) risk factors in African-American population. To achieve our objective, we examined 1900 African-Americans from the Atherosclerosis Risk in Communities study using SNVs identified from whole-genome sequencing data. A total of 971 SNVs found in 726 different mature miRNA-encoding sequences and 16,057 SNVs found in the three prime untranslated region (3'UTR) of 3647 protein-coding genes were identified and interrogated their associations with 17 CVD risk factors. Using single-variant-based approach, we found 5 SNVs in miRNA-encoding sequences to be associated with serum Lipoprotein(a) [Lp(a)], high-density lipoprotein (HDL) or triglycerides, and 2 SNVs in miRNA-target sites to be associated with Lp(a) and HDL, all with false discovery rates of 5%. Using a gene-based approach, we identified 3 pairs of associations between gene NSD1 and platelet count, gene HSPA4L and cardiac troponin T, and gene AHSA2 and magnesium. We successfully validated the association between a variant specific to African-American population, NR_039880.1:n.18A>C, in mature hsa-miR-4727-5p encoding sequence and serum HDL level in an independent sample of 2135 African-Americans. Our study provided candidate miRNAs and their targets for further investigation of their potential contribution to ethnic disparities in CVD risk factors. |
DOI | 10.1007/s00439-017-1858-8 |
Alternate Journal | Hum Genet |
PubMed ID | 29264654 |
PubMed Central ID | PMC5790599 |
Grant List | HHSN268201700002C / HL / NHLBI NIH HHS / United States HHSN268201700001I / HL / NHLBI NIH HHS / United States HHSN268201700004I / HL / NHLBI NIH HHS / United States HHSN268201700004C / HL / NHLBI NIH HHS / United States HHSN268201700003I / HL / NHLBI NIH HHS / United States U54HG003273 / HG / NHGRI NIH HHS / United States RC2 HL102419 / HL / NHLBI NIH HHS / United States 5RC2HL102419 / HL / NHLBI NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States HHSN268201700005C / HL / NHLBI NIH HHS / United States HHSN268201700001C / HL / NHLBI NIH HHS / United States HHSN268201700003C / HL / NHLBI NIH HHS / United States HHSN268201700002I / HL / NHLBI NIH HHS / United States HHSN268201700005I / HL / NHLBI NIH HHS / United States UM1 HG008898 / HG / NHGRI NIH HHS / United States HHSN268201700021C / HL / NHLBI NIH HHS / United States UM1HG008898 / HG / NHGRI NIH HHS / United States |
Genetic variants in microRNA genes and targets associated with cardiovascular disease risk factors in the African-American population.
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