Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

Fox, Ervin R. ; Young, J. Hunter ; Li, Yali ; Dreisbach, Albert W. ; Keating, Brendan J. ; Musani, Solomon K. ; Liu, Kiang ; Morrison, Alanna C. ; Ganesh, Santhi ; Kutlar, Abdullah ; Ramachandran, Vasan S. ; Polak, Josef F. ; Fabsitz, Richard R. ; Dries, Daniel L. ; Farlow, Deborah N. ; Redline, Susan ; Adeyemo, Adebowale ; Hirschorn, Joel N. ; Sun, Yan V. ; Wyatt, Sharon B. ; Penman, Alan D. ; Palmas, Walter ; Rotter, Jerome I. ; Townsend, Raymond R. ; Doumatey, Ayo P. ; Tayo, Bamidele O. ; Mosley, Thomas H. ; Lyon, Helen N. ; Kang, Sun J. ; Rotimi, Charles N. ; Cooper, Richard S. ; Franceschini, Nora ; Curb, J. David ; Martin, Lisa W. ; Eaton, Charles B. ; Kardia, Sharon L.R. ; Taylor, Herman A. ; Caulfield, Mark J. ; Ehret, Georg B. ; Johnson, Toby ; Munroe, Patricia B. ; Rice, Kenneth M. ; Bochud, Murielle ; Johnson, Andrew D. ; Chasman, Daniel I. ; Smith, Albert V. ; Tobin, Martin D. ; Verwoert, Germaine C. ; Hwang, Shih-Jen ; Pihur, Vasyl ; Vollenweider, Peter ; O'Reilly, Paul F. ; Amin, Najaf ; Bragg-Gresham, Jennifer L. ; Teumer, Alexander ; Glazer, Nicole L. ; Launer, Lenore ; Zhao, Jing Hua ; Aulchenko, Yurii ; Heath, Simon ; Sõber, Siim ; Parsa, Afshin ; Luan, Jian'an ; Arora, Pankaj ; Dehghan, Abbas ; Zhang, Feng ; Lucas, Gavin ; Hicks, Andrew A. ; Jackson, Anne U. ; Peden, John F. ; Tanaka, Toshiko ; Wild, Sarah H. ; Rudan, Igor ; Igl, Wilmar ; Milaneschi, Yuri ; Parker, Alex N. ; Fava, Cristiano ; Chambers, John C. ; Kumari, Meena ; JinGo, Min ; van der Harst, Pim ; Kao, Wen Hong Linda ; Sjögren, Marketa ; Vinay, D.G. ; Alexander, Myriam ; Tabara, Yasuharu ; Shaw-Hawkins, Sue ; Whincup, Peter H. ; Liu, Yongmei ; Shi, Gang ; Kuusisto, Johanna ; Seielstad, Mark ; Sim, Xueling ; Nguyen, Khanh-Dung Hoang ; Lehtimäki, Terho ; Matullo, Giuseppe ; Wu, Ying ; Gaunt, Tom R. ; Charlotte Onland-Moret, N. ; Cooper, Matthew N. ; Platou, Carl G.P. ; Org, Elin ; Hardy, Rebecca ; Dahgam, Santosh ; Palmen, Jutta ; Vitart, Veronique ; Braund, Peter S. ; Kuznetsova, Tatiana ; Uiterwaal, Cuno S.P.M. ; Campbell, Harry ; Ludwig, Barbara ; Tomaszewski, Maciej ; Tzoulaki, Ioanna ; Palmer, Nicholette D. ; Aspelund, Thor ; Garcia, Melissa ; Chang, Yen-Pei C. ; O'Connell, Jeffrey R. ; Steinle, Nanette I. ; Grobbee, Diederick E. ; Arking, Dan E. ; Hernandez, Dena ; Najjar, Samer ; McArdle, Wendy L. ; Hadley, David ; Brown, Morris J. ; Connell, John M. ; Hingorani, Aroon D. ; Day, Ian N.M. ; Lawlor, Debbie A. ; Beilby, John P. ; Lawrence, Robert W. ; Clarke, Robert ; Collins, Rory ; Hopewell, Jemma C. ; Ongen, Halit ; Bis, Joshua C. ; Kähönen, Mika ; Viikari, Jorma ; Adair, Linda S. ; Lee, Nanette R. ; Chen, Ming-Huei ; Olden, Matthias ; Pattaro, Cristian ; Hoffman Bolton, Judith A. ; Köttgen, Anna ; Bergmann, Sven ; Mooser, Vincent ; Chaturvedi, Nish ; Frayling, Timothy M. ; Islam, Muhammad ; Jafar, Tazeen H. ; Erdmann, Jeanette ; Kulkarni, Smita R. ; Bornstein, Stefan R. ; Grässler, Jürgen ; Groop, Leif ; Voight, Benjamin F. ; Kettunen, Johannes ; Howard, Philip ; Taylor, Andrew ; Guarrera, Simonetta ; Ricceri, Fulvio ; Emilsson, Valur ; Plump, Andrew ; Barroso, Inês ; Khaw, Kay-Tee ; Weder, Alan B. ; Hunt, Steven C. ; Bergman, Richard N. ; Collins, Francis S. ; Bonnycastle, Lori L. ; Scott, Laura J. ; Stringham, Heather M. ; Peltonen, Leena ; Perola, Markus ; Vartiainen, Erkki ; Brand, Stefan-Martin ; Staessen, Jan A. ; Wang, Thomas J. ; Burton, Paul R. ; SolerArtigas, Maria ; Dong, Yanbin ; Snieder, Harold ; Wang, Xiaoling ; Zhu, Haidong ; Lohman, Kurt K. ; Rudock, Megan E. ; Heckbert, Susan R. ; Smith, Nicholas L. ; Wiggins, Kerri L. ; Shriner, Daniel ; Veldre, Gudrun ; Viigimaa, Margus ; Kinra, Sanjay ; Prabhakaran, Dorairajan ; Tripathy, Vikal ; Langefeld, Carl D. ; Rosengren, Annika ; Thelle, Dag S. ; MariaCorsi, Anna ; Singleton, Andrew ; Forrester, Terrence ; Hilton, Gina ; McKenzie, Colin A. ; Salako, Tunde ; Iwai, Naoharu ; Kita, Yoshikuni ; Ogihara, Toshio ; Ohkubo, Takayoshi ; Okamura, Tomonori ; Ueshima, Hirotsugu ; Umemura, Satoshi ; Eyheramendy, Susana ; Meitinger, Thomas ; Wichmann, H.-Erich ; Cho, Yoon Shin ; Kim, Hyung-Lae ; Lee, Jong-Young ; Scott, James ; Sehmi, Joban S. ; Zhang, Weihua ; Hedblad, Bo ; Nilsson, Peter ; Smith, George Davey ; Wong, Andrew ; Narisu, Narisu ; Stančáková, Alena ; Raffel, Leslie J. ; Yao, Jie ; Kathiresan, Sekar ; O'Donnell, Chris ; Schwartz, Steven M. ; Arfan Ikram, M. ; Longstreth, Will T. ; Seshadri, Sudha ; Shrine, Nick R.G. ; Wain, Louise V. ; Morken, Mario A. ; Swift, Amy J. ; Laitinen, Jaana ; Prokopenko, Inga ; Zitting, Paavo ; Cooper, Jackie A. ; Humphries, Steve E. ; Danesh, John ; Rasheed, Asif ; Goel, Anuj ; Hamsten, Anders ; Watkins, Hugh ; Bakker, Stephan J.L. ; van Gilst, Wiek H. ; Janipalli, Charles S. ; Radha Mani, K. ; Yajnik, Chittaranjan S. ; Hofman, Albert ; Mattace-Raso, Francesco U.S. ; Oostra, Ben A. ; Demirkan, Ayse ; Isaacs, Aaron ; Rivadeneira, Fernando ; Lakatta, Edward G. ; Orru, Marco ; Scuteri, Angelo ; Ala-Korpela, Mika ; Kangas, Antti J. ; Lyytikäinen, Leo-Pekka ; Soininen, Pasi ; Tukiainen, Taru ; Würz, Peter ; Twee-Hee Ong, Rick ; Dörr, Marcus ; Kroemer, Heyo K. ; Völker, Uwe ; Völzke, Henry ; Galan, Pilar ; Hercberg, Serge ; Lathrop, Mark ; Zelenika, Diana ; Deloukas, Panos ; Mangino, Massimo ; Spector, Tim D. ; Zhai, Guangju ; Meschia, James F. ; Nalls, Michael A. ; Sharma, Pankaj ; Terzic, Janos ; Kranthi Kumar, M.J. ; Denniff, Matthew ; Zukowska-Szczechowska, Ewa ; Wagenknecht, Lynne E. ; Fowkes, Gerald R. ; Charchar, Fadi J. ; Schwarz, Peter E.H. ; Hayward, Caroline ; Guo, Xiuqing ; Bots, Michiel L. ; Brand, Eva ; Samani, Nilesh J. ; Polasek, Ozren ; Talmud, Philippa J. ; Nyberg, Fredrik ; Kuh, Diana ; Laan, Maris ; Hveem, Kristian ; Palmer, Lyle J. ; van der Schouw, Yvonne T. ; Casas, Juan P. ; Mohlke, Karen L. ; Vineis, Paolo ; Raitakari, Olli ; Wong, Tien Y. ; Shyong Tai, E. ; Laakso, Markku ; Rao, Dabeeru C. ; Harris, Tamara B. ; Morris, Richard W. ; Dominiczak, Anna F. ; Kivimaki, Mika ; Marmot, Michael G. ; Miki, Tetsuro ; Saleheen, Danish ; Chandak, Giriraj R. ; Coresh, Josef ; Navis, Gerjan ; Salomaa, Veikko ; Han, Bok-Ghee ; Kooner, Jaspal S. ; Melander, Olle ; Ridker, Paul M. ; Bandinelli, Stefania ; Gyllensten, Ulf B. ; Wright, Alan F. ; Wilson, James F. ; Ferrucci, Luigi ; Farrall, Martin ; Tuomilehto, Jaakko ; Pramstaller, Peter P. ; Elosua, Roberto ; Soranzo, Nicole ; Sijbrands, Eric J.G. ; Altshuler, David ; Loos, Ruth J.F. ; Shuldiner, Alan R. ; Gieger, Christian ; Meneton, Pierre ; Uitterlinden, Andre G. ; Wareham, Nicholas J. ; Gudnason, Vilmundur ; Rettig, Rainer ; Uda, Manuela ; Strachan, David P. ; Witteman, Jacqueline C.M. ; Hartikainen, Anna-Liisa ; Beckmann, Jacques S. ; Boerwinkle, Eric ; Boehnke, Michael ; Larson, Martin G. ; Järvelin, Marjo-Riitta ; Psaty, Bruce M. ; Abecasis, Gonçalo R. ; Elliott, Paul ; van Duijn, Cornelia M. ; Newton-Cheh, Christopher ; Chakravarti, Aravinda ; Zhu, Xiaofeng ; Levy, Daniel

In: Human Molecular Genetics, 2011, vol. 20, no. 11, p. 2273-2284

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    Summary
    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