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Genome sequencing unveils a regulatory landscape of platelet reactivity.

Publication ,  Journal Article
Keramati, AR; Chen, M-H; Rodriguez, BAT; Yanek, LR; Bhan, A; Gaynor, BJ; Ryan, K; Brody, JA; Zhong, X; Wei, Q; Kammers, K; Kanchan, K; Li, B ...
Published in: Nat Commun
June 15, 2021
Published version (DOI) Link to item

Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) participants deeply phenotyped for platelet aggregation. We identify the RGS18 locus, which encodes a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with expression quantitative trait loci (eQTL) signatures for RGS18 expression in platelets. Gene-based approaches implicate the SVEP1 gene, a known contributor of coronary artery disease risk. Sentinel variants at RGS18 and PEAR1 are associated with thrombosis risk and increased gastrointestinal bleeding risk, respectively. Our WGS findings add to previously identified GWAS loci, provide insights regarding the mechanism(s) by which genetics may influence cardiovascular disease risk, and underscore the importance of rare variant and regulatory approaches to identifying loci contributing to complex phenotypes.

Duke Scholars

Allison Elizabeth Ashley-Koch
Author Allison Elizabeth Ashley-Koch Medicine, Nephrology
Yongmei Liu
Author Yongmei Liu Medicine, Cardiology
Marilyn Jo Telen
Author Marilyn Jo Telen Medicine, Hematology
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Published In

Nat Commun

DOI

10.1038/s41467-021-23470-9

EISSN

2041-1723

Publication Date

June 15, 2021

Volume

12

Issue

1

Start / End Page

3626

Location

England

Related Subject Headings

  • Whole Genome Sequencing
  • Thrombosis
  • Receptors, Cell Surface
  • RGS Proteins
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Platelet Function Tests
  • Platelet Aggregation
  • Phenotype
  • K562 Cells
 

Citation

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MLA
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Keramati, A. R., Chen, M.-H., Rodriguez, B. A. T., Yanek, L. R., Bhan, A., Gaynor, B. J., … Johnson, A. D. (2021). Genome sequencing unveils a regulatory landscape of platelet reactivity. Nat Commun, 12(1), 3626. https://doi.org/10.1038/s41467-021-23470-9
Keramati, Ali R., Ming-Huei Chen, Benjamin A. T. Rodriguez, Lisa R. Yanek, Arunoday Bhan, Brady J. Gaynor, Kathleen Ryan, et al. “Genome sequencing unveils a regulatory landscape of platelet reactivity.” Nat Commun 12, no. 1 (June 15, 2021): 3626. https://doi.org/10.1038/s41467-021-23470-9.
Keramati AR, Chen M-H, Rodriguez BAT, Yanek LR, Bhan A, Gaynor BJ, et al. Genome sequencing unveils a regulatory landscape of platelet reactivity. Nat Commun. 2021 Jun 15;12(1):3626.
Keramati, Ali R., et al. “Genome sequencing unveils a regulatory landscape of platelet reactivity.” Nat Commun, vol. 12, no. 1, June 2021, p. 3626. Pubmed, doi:10.1038/s41467-021-23470-9.
Keramati AR, Chen M-H, Rodriguez BAT, Yanek LR, Bhan A, Gaynor BJ, Ryan K, Brody JA, Zhong X, Wei Q, NHLBI Trans-Omics for Precision (TOPMed) Consortium, Kammers K, Kanchan K, Iyer K, Kowalski MH, Pitsillides AN, Cupples LA, Li B, Schlaeger TM, Shuldiner AR, O’Connell JR, Ruczinski I, Mitchell BD, Faraday N, Taub MA, Becker LC, Lewis JP, Mathias RA, Johnson AD. Genome sequencing unveils a regulatory landscape of platelet reactivity. Nat Commun. 2021 Jun 15;12(1):3626.

Published In

Nat Commun

DOI

10.1038/s41467-021-23470-9

EISSN

2041-1723

Publication Date

June 15, 2021

Volume

12

Issue

1

Start / End Page

3626

Location

England

Related Subject Headings

  • Whole Genome Sequencing
  • Thrombosis
  • Receptors, Cell Surface
  • RGS Proteins
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Platelet Function Tests
  • Platelet Aggregation
  • Phenotype
  • K562 Cells