Scientific article
Open access

Analysis of putative cis-regulatory elements regulating blood pressure variation

Published inHuman molecular genetics, vol. 29, no. 11, p. 1922-1932
Publication date2020-07-21

Hundreds of loci have been associated with blood pressure (BP) traits from many genome-wide association studies. We identified an enrichment of these loci in aorta and tibial artery expression quantitative trait loci in our previous work in ~100 000 Genetic Epidemiology Research on Aging study participants. In the present study, we sought to fine-map known loci and identify novel genes by determining putative regulatory regions for these and other tissues relevant to BP. We constructed maps of putative cis-regulatory elements (CREs) using publicly available open chromatin data for the heart, aorta and tibial arteries, and multiple kidney cell types. Variants within these regions may be evaluated quantitatively for their tissue-or cell-type-specific regulatory impact using deltaSVM functional scores, as described in our previous work. We aggregate variants within these putative CREs within 50 Kb of the start or end of 'expressed' genes in these tissues or cell types using public expression data and use deltaSVM scores as weights in the group-wise sequence kernel association test to identify candidates. We test for association with both BP traits and expression within these tissues or cell types of interest and identify the candidates MTHFR, C10orf32, CSK, NOV, ULK4, SDCCAG8, SCAMP5, RPP25, HDGFRP3, VPS37B and PPCDC. Additionally, we examined two known QT interval genes, SCN5A and NOS1AP, in the Atherosclerosis Risk in Communities Study, as a positive control, and observed the expected heart-specific effect. Thus, our method identifies variants and genes for further functional testing using tissue-or cell-type-specific putative regulatory information.

  • Aorta / physiopathology
  • Atherosclerosis / genetics
  • Atherosclerosis / physiopathology
  • Blood Pressure / genetics
  • Blood Pressure / physiology
  • Chromatin
  • Gene Expression Regulation / genetics
  • Genome-Wide Association Study
  • Heart / physiopathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Kidney / physiopathology
  • Membrane Proteins / genetics
  • Quantitative Trait Loci / genetics
  • Regulatory Sequences, Nucleic Acid / genetics
  • Tibial Arteries / physiopathology
  • NIA NIH HHS - [RC2 AG036607]
  • NCRR NIH HHS - [UL1 RR025005]
  • NHLBI NIH HHS - [HHSN268201100007C]
  • NHLBI NIH HHS - [HHSN268201100011C]
  • NHLBI NIH HHS - [R01 HL086694]
  • NHGRI NIH HHS - [U01 HG004402]
  • NHLBI NIH HHS - [HHSN268201100012C]
  • NHLBI NIH HHS - [HHSN268201100005C]
  • NHLBI NIH HHS - [HHSN268201100006C]
  • NHLBI NIH HHS - [HHSN268201100010C]
  • NHLBI NIH HHS - [HHSN268201100008C]
  • NIGMS NIH HHS - [R01 GM104469]
  • NHLBI NIH HHS - [R01 HL087641]
  • NHLBI NIH HHS - [HHSN268201100009C]
  • National Heart, Lung, and Blood Institute - [R01HL086694]
  • Robert Wood Johnson Foundation -
  • National Institutes of Health - [HHSN268200625226C]
  • Kaiser Permanente Community Benefit Programs -
  • Wayne and Gladys Valley Foundation -
  • National Human Genome Research Institute - [U01HG004402]
  • Foundation of Medical Researchers -
  • National Institutes of Health Roadmap for Medical Research - [UL1RR025005]
  • Ellison Medical Foundation -
  • Geneva University Hospitals -
Citation (ISO format)
NANDAKUMAR, Priyanka et al. Analysis of putative cis-regulatory elements regulating blood pressure variation. In: Human molecular genetics, 2020, vol. 29, n° 11, p. 1922–1932. doi: 10.1093/hmg/ddaa098
Main files (1)
Article (Published version)
ISSN of the journal0964-6906

Technical informations

Creation06/30/2022 9:33:00 AM
First validation06/30/2022 9:33:00 AM
Update time03/16/2023 7:31:25 AM
Status update03/16/2023 7:31:24 AM
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