Genetic variants in microRNA genes and targets associated with cardiovascular disease risk factors in the African-American population.

TitleGenetic variants in microRNA genes and targets associated with cardiovascular disease risk factors in the African-American population.
Publication TypeJournal Article
Year of Publication2018
AuthorsLi, C, Grove, ML, Yu, B, Jones, BC, Morrison, A, Boerwinkle, E, Liu, X
JournalHum Genet
Volume137
Issue1
Pagination85-94
Date Published2018 Jan
ISSN1432-1203
Keywords3' Untranslated Regions, Adult, African Americans, 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.

DOI10.1007/s00439-017-1858-8
Alternate JournalHum. Genet.
PubMed ID29264654
PubMed Central IDPMC5790599
Grant ListRC2 HL102419 / HL / NHLBI NIH HHS / United States
U54HG003273 / / National Human Genome Research Institute /
U54 HG003273 / HG / NHGRI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
5RC2HL102419 / / National Heart, Lung, and Blood Institute /
HHSN268201700002I / HL / NHLBI NIH HHS / United States
UM1 HG008898 / HG / NHGRI NIH HHS / United States
UM1HG008898 / / National Human Genome Research Institute /