Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study
Ervin R. Fox, J. Hunter Young, Yali Li, Albert W. Dreisbach, Brendan J. Keating(Translational Therapeutics (United States)), Solomon K. Musani, Kiang Liu(Northwestern University), Alanna C. Morrison(The University of Texas Health Science Center at Houston), Santhi K. Ganesh(Michigan Medicine), Abdullah Kutlar(Augusta University), Ramachandran S. Vasan(Boston University), Josef F. Polak(Tufts Medical Center), Richard R. Fabsitz(Research Applications (United States)), Daniel L. Dries(University of Pennsylvania), Deborah Farlow(Broad Institute), Susan Redline(Case Western Reserve University), Adebowale Adeyemo(National Human Genome Research Institute), Joel N. Hirschorn(Boston Children's Hospital), Yan V. Sun(University of Michigan), Sharon B. Wyatt(University of Mississippi Medical Center), Alan D. Penman, Walter Palmas(Columbia University), Jerome I. Rotter(Cedars-Sinai Medical Center), Raymond R. Townsend(University of Pennsylvania), Ayo P. Doumatey(National Human Genome Research Institute), Bamidele O. Tayo(Loyola University Chicago), Thomas H. Mosley, Helen N. Lyon(Boston Children's Hospital), Sun Jung Kang, Charles N. Rotimi(National Human Genome Research Institute), Richard S. Cooper(Loyola University Chicago), Nora Franceschini(University of North Carolina at Chapel Hill), J. David Curb(Pacific Health Research and Education Institute), Lisa W. Martin(George Washington University), Charles B. Eaton(Brown University), Sharon L. R. Kardia(University of Michigan), Herman A. Taylor, Mark J. Caulfield(Queen Mary University of London), Georg Ehret(Johns Hopkins University), Toby Johnson(Queen Mary University of London), Patricia B. Munroe, Kenneth Rice, Murielle Bochud, Andrew D. Johnson(Queen Mary University of London), Daniel I. Chasman, Albert V. Smith, Martin D. Tobin, Germaine C. Verwoert, Shih‐Jen Hwang, Vasyl Pihur, Péter Vollenweider, Paul F. O’Reilly, Najaf Amin, Jennifer L. Bragg‐Gresham, Alexander Teumer, Nicole L. Glazer, Lenore J. Launer, Jing Zhao, Yurii S. Aulchenko, Simon Heath, Siim Sõber, Afshin Parsa, Jian’an Luan, Pankaj Arora, Abbas Dehghan, Feng Zhang, Gavin Lucas, Andrew A. Hicks, Anne Jackson, John F. Peden, Toshiko Tanaka, Sarah H. Wild, Igor Rudan, Wilmar Igl, Yuri Milaneschi, Alex Parker, Cristiano Fava, John C. Chambers, Meena Kumari, Min JinGo, Pim van der Harst, Wen Hong Linda Kao, Marketa Sjögren, D. G. Vinay, M Alexander, Yasuharu Tabara, Sue Shaw‐Hawkins, Peter H. Whincup, Ching‐Ti Liu(Northwestern University), Gang Shi, Johanna Kuusisto, Mark Seielstad(Queen Mary University of London), Xueling Sim, Khanh‐Dung H. Nguyen, Terho Lehtimäki, Giuseppe Matullo, Ying Wu, Tom R. Gaunt, N. Charlotte Onland‐Moret(National Institutes of Health), Matthew N. Cooper(Loyola University Chicago), Carl Platou, Elin Org(University of Geneva), Rebecca Hardy, Santosh Dahgam, Jutta Palmen, Véronique Vitart, Peter S. Braund, Tatiana Kuznetsova, Cuno S.P.M. Uiterwaal, Harry Campbell, Barbara Ludwig, Maciej Tomaszewski, Ioanna Tzoulaki, Nicholette D. Palmer, Thor Aspelund, Melissa García, Yen-Pei C. Chang, Jeffrey R. O’Connell, Nanette Steinle, Diederick E. Grobbee, Dan E. Arking, Dena Hernandez, Samer S. Najjar, Wendy L. McArdle, David Hadley(Pacific Health Research and Education Institute), Morris J. Brown, John Connell, Aroon D. Hingorani, Ian N. M. Day, Debbie A. Lawlor, John Beilby, Robert Lawrence, Robert Clarke, Rory Collins, Jemma C. Hopewell, Halit Ongen, Joshua C. Bis, Mika Kähönen, Jorma Viikari, Linda S. Adair, Sang Lee, Ming‐Huei Chen, Matthias Olden, Cristian Pattaro, Judith A. Hoffman Bolton, Anna Köttgen(The University of Texas at Austin), Sven Bergmann, Vincent Mooser, Nish Chaturvedi, Timothy M. Frayling, Muhammad Islam, Tazeen H. Jafar, Jeanette Erdmann, Smita Kulkarni, Stefan R. Bornstein, Jürgen Gräßler, Leif Groop, Benjamin F. Voight, Johannes Kettunen, Philip Howard, Andrew M. Taylor, Simonetta Guarrera, Fulvio Ricceri, Valur Emilsson, Andrew Plump, Inês Barroso, Kay‐Tee Khaw, Alan B. Weder, Steven C. Hunt, Richard N. Bergman, Francis S. Collins, Lori L. Bonnycastle, Laura J. Scott, Heather M. Stringham, Leena Peltonen, Markus Perola, Erkki Vartiainen, Stefan‐Martin Brand, Jan A. Staessen, Thomas J. Wang, Paul R. Burton, María Soler Artigas, Yanbin Dong, Harold Snieder, Xiaoling Wang, Haidong Zhu, Kurt K. Lohman, Megan E. Rudock, Susan R. Heckbert(Case Western Reserve University), Nicholas L. Smith, Kerri L. Wiggins, Daniel Shriner(National Institutes of Health), Gudrun Veldre, Margus Viigimaa, Sanjay Kinra, Dorairaj Prabhakaran, Vikal Tripathy, Carl D. Langefeld, Annika Rosengren, Dag S. Thelle, Anna MariaCorsi(The University of Texas at Austin), Andrew Singleton, Terrence Forrester, Gina M. Hilton, Colin A. McKenzie, Tunde Salako, Naoharu Iwai, Yoshikuni Kita, Toshio Ogihara, Takayoshi Ohkubo, Tomonori Okamura, Hirotsugu Ueshima, Satoshi Umemura, S. Eyheramendy, Thomas Meitinger, H.‐Erich Wichmann, Yoon Shin Cho(Harvard University Press), Hyung-Lae Kim, Jong‐Young Lee, James Scott, Joban Sehmi, Weihua Zhang, Bo Hedblad(National Human Genome Research Institute), Peter Nilsson, George Davey Smith, Andrew Wong, Narisu Narisu, Alena Stančáková, Leslie J. Raffel, Jie Yao, Sekar Kathiresan, Chris O’Donnell, Steven M. Schwartz, M. Arfan Ikram(Queen Mary University of London), W. T. Longstreth, Sudha Seshadri, Nick Shrine, Louise V. Wain, Mario A. Morken, Amy J. Swift, Laitinen Jaana, Inga Prokopenko, Paavo Zitting, Jackie A. Cooper(Loyola University Chicago), Steve E. Humphries, John Danesh(Queen Mary University of London), Asif Rasheed, Anuj Goel, Anders Hamsten, Hugh Watkins, Stephan J. L. Bakker, Wiek H. van Gilst, Charles S. Janipalli, K. Radha Mani(Johns Hopkins University), Chittaranjan S. Yajnik, Albert Hofman, Francesco Mattace‐Raso, Ben A. Oostra, Ayşe Demirkan, Aaron Isaacs, Fernando Rivadeneira, Edward G. Lakatta, Marco Orrù, Angelo Scuteri, Mika Ala‐Korpela, Antti J. Kangas, Leo‐Pekka Lyytikäinen, Pasi Soininen, Taru Tukiainen, P. Wurz, Rick Twee‐Hee Ong, Marcus Dörr, Heyo K. Kroemer, Uwe Völker, Henry Völzke, Pilar Galán, Serge Herçberg, Mark Lathrop(Queen Mary University of London), Diana Zélénika, Panos Deloukas, Massimo Mangino, Tim D. Spector, Guangju Zhai, James F. Meschia, Michael A. Nalls, Pankaj Sharma, Janoš Terzić, G Anil Kumar, Matthew Denniff, E Zukowska-Szczechowska, Lynne E. Wagenknecht, Gerald R. Fowkes, Fadi J. Charchar, Peter Schwarz, Caroline Hayward, Xiuqing Guo, Michiel L. Bots, Eva Brand, Nilesh J. Samani, Ozren Polašek, Philippa J. Talmud, Fredrik Nyberg, Diana Kuh, Maris Laan, Kristian Hveem, Lyle J. Palmer, Yvonne T. van der Schouw, Juan P. Casas, Karen L. Mohlke, Paolo Vineis, Olli T. Raitakari, Tien Yin Wong, E. Shyong Tai(National Institutes of Health), Markku Laakso, D. C. Rao, Tamara B. Harris, Richard Morris(The University of Texas at Austin), Anna F. Dominiczak, Mika Kivimäki, Michael Marmot, Tetsuro Miki, Danish Saleheen, Giriraj R. Chandak, Josef Coresh(Tufts University), Gerjan Navis, Veikko Salomaa, Bok‐Ghee Han, Jaspal S. Kooner, Olle Melander, Paul M. Ridker, Stefania Bandinelli, Ulf Gyllensten, Alan F. Wright, James F. Wilson, Luigi Ferrucci, Martin Farrall(George Washington University), Jaakko Tuomilehto, Peter P. Pramstaller, Roberto Elosúa, Nicole Soranzo, Eric J.G. Sijbrands, David Altshuler(Pacific Health Research and Education Institute), Ruth J. F. Loos, Alan R. Shuldiner, Christian Gieger, Pierre Meneton, André G. Uitterlinden, Nicholas J. Wareham, Vilmundur Guðnason, Rainer Rettig, Manuela Uda, David P. Strachan, Jacqueline C.M. Witteman, Anna‐Liisa Hartikainen, J. Beckmann, Eric Boerwinkle, Michael Boehnke, Martin G. Larson, Marjo‐Riitta Järvelin, Bruce M. Psaty, Gonçalo R. Abecasis, Paul Elliott, Cornelia M. van Duijn, Christopher Newton‐Cheh, Aravinda Chakravarti(Johns Hopkins University), Xiaofeng Zhu, Daniel Levy(National Heart Lung and Blood Institute)
Cited by 173Open Access
Abstract
The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.
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