Author
He, Karen YKelly, Tanika N
Wang, Heming
Liang, Jingjing
Zhu, Luke
Cade, Brian E
Assimes, Themistocles L
Becker, Lewis C
Beitelshees, Amber L
Bielak, Lawrence F
Bress, Adam P
Brody, Jennifer A
Chang, Yen-Pei Christy
Chang, Yi-Cheng
de Vries, Paul S
Duggirala, Ravindranath
Fox, Ervin R
Franceschini, Nora
Furniss, Anna L
Gao, Yan
Guo, Xiuqing
Haessler, Jeffrey
Hung, Yi-Jen
Hwang, Shih-Jen
Irvin, Marguerite Ryan
Kalyani, Rita R
Liu, Ching-Ti
Liu, Chunyu
Martin, Lisa Warsinger
Montasser, May E
Muntner, Paul M
Mwasongwe, Stanford
Naseri, Take
Palmas, Walter
Reupena, Muagututi'a Sefuiva
Rice, Kenneth M
Sheu, Wayne H-H
Shimbo, Daichi
Smith, Jennifer A
Snively, Beverly M
Yanek, Lisa R
Zhao, Wei
Blangero, John
Boerwinkle, Eric
Chen, Yii-Der Ida
Correa, Adolfo
Cupples, L Adrienne
Curran, Joanne E
Fornage, Myriam
He, Jiang
Hou, Lifang
Kaplan, Robert C
Kardia, Sharon L R
Kenny, Eimear E
Kooperberg, Charles
Lloyd-Jones, Donald
Loos, Ruth J F
Mathias, Rasika A
McGarvey, Stephen T
Mitchell, Braxton D
North, Kari E
Peyser, Patricia A
Psaty, Bruce M
Raffield, Laura M
Rao, D C
Redline, Susan
Reiner, Alex P
Rich, Stephen S
Rotter, Jerome I
Taylor, Kent D
Tracy, Russell
Vasan, Ramachandran S
Morrison, Alanna C
Levy, Daniel
Chakravarti, Aravinda
Arnett, Donna K
Zhu, Xiaofeng
Date
2022-02-19Journal
BMC GenomicsPublisher
Springer NatureType
Article
Metadata
Show full item recordAbstract
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.Rights/Terms
© 2022. The Author(s).Identifier to cite or link to this item
http://hdl.handle.net/10713/18094ae974a485f413a2113503eed53cd6c53
10.1186/s12864-022-08356-4
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