Rare coding variants in RCN3 are associated with blood pressure

  • Karen Y. He (Creator)
  • Tanika Kelly (Creator)
  • Heming Wang (Creator)
  • Jingjing Liang (Creator)
  • Luke Zhu (Creator)
  • Brian E. Cade (Creator)
  • Themistocles L. Assimes (Creator)
  • L. C. Becker (Creator)
  • Amber L. Beitelshees (Creator)
  • Lawrence F. Bielak (Creator)
  • Adam Bress (Creator)
  • Jennifer Brody (Creator)
  • Yen Pei Christy Chang (Creator)
  • Yi Cheng Chang (Creator)
  • Paul S. De Vries (Creator)
  • R. Duggirala (Creator)
  • Ervin R. Fox (Creator)
  • Nora Franceschini (Creator)
  • Anna L. Furniss (Creator)
  • Yan Gao (Creator)
  • Xiuqing Guo (Creator)
  • Jeffrey Haessler (Creator)
  • Yi Jen Hung (Creator)
  • Shih Jen Hwang (Creator)
  • Marguerite R. Irvin (Creator)
  • Rita Rastogi Kalyani (Creator)
  • Ching Ti Liu (Creator)
  • Chunyu Liu (Creator)
  • Lisa W. Martin (Creator)
  • May E. Montasser (Creator)
  • Paul Muntner (Creator)
  • Stanford Mwasongwe (Creator)
  • Take Naseri (Creator)
  • Walter Palmas (Creator)
  • Muagututi'a Sefuiva Reupena (Creator)
  • Kenneth Rice (Creator)
  • Wayne H.H. Sheu (Creator)
  • Daichi Shimbo (Creator)
  • Jennifer A. Smith (Creator)
  • B. Snively (Creator)
  • Lisa R. Yanek (Creator)
  • Wei Zhao (Creator)
  • J. Blangero (Creator)
  • Eric Boerwinkle (Creator)
  • Yii Der Ida Chen (Creator)
  • Adolfo Correa (Creator)
  • L. A. Cupples (Creator)
  • Joanne E. Curran (Creator)
  • Myriam Fornage (Creator)
  • Jiang He (Creator)
  • Lifang Hou (Creator)
  • Panos Deloukas (Creator)
  • Sharon L.R. Kardia (Creator)
  • Eimear E. Kenny (Creator)
  • Charles Kooperberg (Creator)
  • Donald M Lloyd-Jones (Creator)
  • Ruth Loos (Creator)
  • Rasika A. Mathias (Creator)
  • S. T. McGarvey (Creator)
  • Braxton D. Mitchell (Creator)
  • Kari E. North (Creator)
  • Patricia Peyser (Creator)
  • Bruce M. Psaty (Creator)
  • Laura Raffield (Creator)
  • Dabeeru C. Rao (Creator)
  • S. Redline (Creator)
  • Alexander P. Reiner (Creator)
  • Stephen S. Rich (Creator)
  • Jerome I. Rotter (Creator)
  • K. Taylor (Creator)
  • Russell P. Tracy (Creator)
  • Vasan S. Ramachandran (Creator)
  • A. C. Morrison (Creator)
  • Daniel Levy (Creator)
  • Aravinda Chakravarti (Creator)
  • Donna K. Arnett (Creator)
  • Anna F. Dominiczak (Creator)



Abstract Background While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries. Results Associations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10− 7). Conclusions Low frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.
Date made available2022
  • Rare coding variants in RCN3 are associated with blood pressure

    The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Dec 2022, In: BMC Genomics. 23, 1, 148.

    Research output: Contribution to journalArticlepeer-review

    Open Access
    1 Scopus citations

Cite this