@article{9233f150e06046ef9869291dbe9d3d63,
title = "Rare coding variants in RCN3 are associated with blood pressure",
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.",
keywords = "Blood pressure, Rare variant analysis, Whole genome sequencing",
author = "{The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium} and He, {Karen Y.} and Kelly, {Tanika N.} and Heming Wang and Jingjing Liang and Luke Zhu and Cade, {Brian E.} and Assimes, {Themistocles L.} and Becker, {Lewis C.} and Beitelshees, {Amber L.} and Bielak, {Lawrence F.} and Bress, {Adam P.} and Brody, {Jennifer A.} and Chang, {Yen Pei Christy} and Chang, {Yi Cheng} and {de Vries}, {Paul S.} and Ravindranath Duggirala and Fox, {Ervin R.} and Nora Franceschini and Furniss, {Anna L.} and Yan Gao and Xiuqing Guo and Jeffrey Haessler and Hung, {Yi Jen} and Hwang, {Shih Jen} and Irvin, {Marguerite Ryan} and Kalyani, {Rita R.} and Liu, {Ching Ti} and Chunyu Liu and Martin, {Lisa Warsinger} and Montasser, {May E.} and Muntner, {Paul M.} and Stanford Mwasongwe and Take Naseri and Walter Palmas and Reupena, {Muagututi{\textquoteright}a Sefuiva} and Rice, {Kenneth M.} and Sheu, {Wayne H.H.} and Daichi Shimbo and Smith, {Jennifer A.} and Snively, {Beverly M.} and Yanek, {Lisa R.} and Wei Zhao and John Blangero and Eric Boerwinkle and Chen, {Yii Der Ida} and Adolfo Correa and Cupples, {L. Adrienne} and Curran, {Joanne E.} and Myriam Fornage and Jiang He and Lifang Hou and Kaplan, {Robert C.} and Kardia, {Sharon L.R.} and Kenny, {Eimear E.} and Charles Kooperberg and Donald Lloyd-Jones and Loos, {Ruth J.F.} and Mathias, {Rasika A.} and McGarvey, {Stephen T.} and Mitchell, {Braxton D.} and North, {Kari E.} and Peyser, {Patricia A.} and Psaty, {Bruce M.} and Raffield, {Laura M.} and Rao, {D. C.} and Susan Redline and Reiner, {Alex P.} and Rich, {Stephen S.} and Rotter, {Jerome I.} and Taylor, {Kent D.} and Russell Tracy and Vasan, {Ramachandran S.} and Morrison, {Alanna C.} and Daniel Levy and Aravinda Chakravarti and Arnett, {Donna K.} and Xiaofeng Zhu",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1186/s12864-022-08356-4",
language = "English",
volume = "23",
journal = "BMC genomics",
issn = "1471-2164",
number = "1",
}