Comparative and Functional Genomic Resource for Mechanistic Studies of Human Blood Pressure–Associated Single Nucleotide Polymorphisms

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2020-03, Vol.75 (3), p.859-868
• Main Authors: Mishra, Manoj K., Liang, Eugene Y., Geurts, Aron M., Auer, Paul W.L., Liu, Pengyuan, Rao, Sridhar, Greene, Andrew S., Liang, Mingyu, Liu, Yong
• Format: Article
• Language: English
• Subjects: Animals; Blood Pressure - genetics; Blood Pressure - physiology; CCCTC-Binding Factor - metabolism; Cell Adhesion Molecules - biosynthesis; Cell Adhesion Molecules - genetics; Deep Learning; Enhancer Elements, Genetic - genetics; Genetic Predisposition to Disease; Haplotypes - genetics; Humans; Linkage Disequilibrium; Mice - genetics; MicroRNAs - genetics; Models, Genetic; Mutagenesis, Site-Directed; Nucleic Acid Conformation; Nucleotide Motifs; Polymorphism, Single Nucleotide; Proof of Concept Study; Protein Binding; Quantitative Trait Loci; RNA Splicing; RNA, Long Noncoding - genetics; RNA, Messenger - genetics; Synteny; Transcription Factors - metabolism
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.119.14109

The objective of the current study is to use comparative and functional genomic analysis to help to understand the biological mechanism mediating the effect of single nucleotide polymorphisms (SNPs) on blood pressure. We mapped 26 585 SNPs that are in linkage disequilibrium with 1071 human blood pressure–associated sentinel SNPs to 9447 syntenic regions in the mouse genome. Approximately 21.8% of the 1071 linkage disequilibrium regions are located at least 10 kb from any protein-coding gene. Approximately 300 blood pressure–associated SNPs are expression quantitative trait loci for a few dozen known blood pressure physiology genes in tissues including specific kidney regions. Blood pressure–associated sentinel SNPs are significantly enriched for expression quantitative trait loci for blood pressure physiology genes compared with randomly selected SNPs (P