Year: 2024
Type: article
Study design: Observational Study
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.
DOI: 10.17615/y07d-kq52
Authors: Tracy, R., Liu, C.-T., Furniss, A.L., Vasan, R.S., Peyser, P.A., Gao, Y., Kardia, S.L.R., Psaty, B.M., Rotter, J.I., de Vries, P.S., Bress, A.P., Brody, J.A., Loos, R.J.F., Chang, Y.-P.C., Chang, Y.-C., Arnett, D.K., Mwasongwe, S., Zhu, X., Boerwinkle, E., Naseri, T., Raffield, L.M., Chen, Y.-D.I., Rao, D.C., Redline, S., Wang, H., Liang, J., Zhu, L., Snively, B.M., Yanek, L.R., Smith, J.A., Mitchell, B.D., Kenny, E.E., Cupples, L.A., Curran, J.E., Reupena, M.S., Rice, K.M., Kelly, T.N., Morrison, A.C., Fornage, M., Martin, L.W., Levy, D., Montasser, M.E., The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, He, K.Y., Zhao, W., Liu, C., Blangero, J., McGarvey, S.T., Hwang, S.-J., Palmas, W., Taylor, K.D., Mathias, R.A., Kaplan, R.C., Duggirala, R., Fox, E.R., Franceschini, N., Chakravarti, A., Reiner, A.P., Rich, S.S., North, K.E., Haessler, J., Kooperberg, C., Hung, Y.-J., Lloyd-Jones, D., Sheu, W.H.-H., Shimbo, D., Guo, X., He, J., Hou, L., Muntner, P.M., Cade, B.E., Assimes, T.L., Becker, L.C., Beitelshees, A.L., Bielak, L.F., Correa, A., Irvin, M.R., Kalyani, R.R., NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Health and Human Services, Office of Dietary Supplements, U.S. Department of Veterans Affairs, American Heart Association, Women's Health Initiative, Brown University, Jackson State University, Northwestern University, San Diego State University, George Washington University, School of Medicine, Boston University, University of Washington, Johns Hopkins University, Genomic Health, University of Texas Health Science Center at Houston, Broad Institute, McGovern Medical School, Mississippi State Department of Health, Taichung Veterans General Hospital, National Institutes of Health, University of Illinois at Urbana-Champaign, University of North Carolina at Chapel Hill, Feinberg School of Medicine, Wake Forest School of Medicine, Irving Medical Center, Columbia University, Larner College of Medicine, University of Vermont, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Eye Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Dental and Craniofacial Research, National Center for Research Resources, NIH Clinical Center, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
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OpenAlex ID: W4400023535