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

Fox, Er; Young, Jh; Y, Li; Dreisbach, Aw; Keating, Bj; Musani, Sk; Liu, K; Morrison, Ac; Ganesh, S; Kutlar, A; Ramachandran, Vs; Polak, Jf; Fabsitz, Rr; Dries, Dl; Farlow, Dn; Redline, S; Adeyemo, A; Hirschorn, Jn; Sun, Yv; Wyatt, Sb; Penman, Ad; Palmas, W; Rotter, Ji; Townsend, Rr; Doumatey, Ap; Tayo, Bo; Mosley TH Jr,; Lyon, Hn; Kang, Sj; Rotimi, Cn; Cooper, Rs; Franceschini, N; Curb, Jd; Martin, Lw; Eaton, Cb; Kardia, Sl; Taylor, Ha; Caulfield, Mj; Ehret, Gb; Johnson, T; International Consortium for Blood Pressure Genome wide Association Studies,; Chakravarti, A; Zhu, X; Levy, D.; Munroe, Pb; Rice, Km; Bochud, M; Johnson, Ad; Chasman, Di; Smith, Av; Tobin, Md; Verwoert, Gc; Hwang, Sj; Pihur, V; Vollenweider, P; O'Reilly, Pf; Amin, N; Bragg Gresham JL,; Teumer, A; Glazer, Nl; Launer, L; Zhao, Jh; Aulchenko, Y; Heath, S; Sõber, S; Parsa, A; Luan, J; Arora, P; Dehghan, A; Zhang, F; Lucas, G; Hicks, Aa; Jackson, Au; Peden, Jf; Tanaka, T; Wild, Sh; Rudan, I; Igl, W; Milaneschi, Y; Parker, An; Fava, C; Chambers, Jc; Kumari, M; Mj, Go; van der Harst, P; Kao, Wh; Sjögren, M; Vinay, Dg; Alexander, M; Tabara, Y; Shaw Hawkins, S; Whincup, Ph; Liu, Y; Shi, G; Kuusisto, J; Seielstad, M; Sim, X; Nguyen, Kd; Lehtimäki, T; Matullo, Giuseppe; Y, Wu; Gaunt, T; Onland Moret NC,; Cooper, Mn; Platou, Cg; Org, E; Hardy, R; Dahgam, S; Palmen, J; Vitart, V; Braund, P; Kuznetsova, T; Uiterwaal, Cs; Campbell, H; Ludwig, B; Tomaszewski, M; Tzoulaki, I; Palmer, Nd; Consortium, Cardiogram; Consortium, Ckdgen; Consortium, Kidneygen; Consortium, Echogen; CHARGE HF consortium,; Aspelund, T; Garcia, M; Chang, Yp; O'Connell, Jr; Steinle, Ni; Grobbee, De; Arking, De; Hernandez, D; Najjar, S; Mcardle, Wl; Hadley, D; Brown, Mj; Connell, Jm; Hingorani, Ad; Day, In; Lawlor, Da; Beilby, Jp; Lawrence, Rw; Clarke, R; Collins, R; Hopewell, Jc; Ongen, H; Bis, Jc; Kähönen, M; Viikari, J; Adair, Ls; Lee, Nr; Chen, Mh; Olden, M; Pattaro, C; Hoffman Bolton JA,; Köttgen, A; Bergmann, S; Mooser, V; Chaturvedi, N; Frayling, Tm; Islam, M; Jafar, Th; Erdmann, J; Kulkarni, Sr; Bornstein, Sr; Grässler, J; Groop, L; Voight, Bf; Kettunen, J; Howard, P; Taylor, A; Guarrera, Simonetta; Ricceri, Fulvio; Emilsson, V; Plump, A; Barroso, I; Khaw, Kt; Weder, Ab; Hunt, Sc; Bergman, Rn; Collins, Fs; Bonnycastle, Ll; Scott, Lj; Stringham, Hm; Peltonen, L; Perola, M; Vartiainen, E; Brand, Sm; Staessen, Ja; Wang, Tj; Burton, Pr; Soler Artigas, M; Dong, Y; Snieder, H; Wang, X; Zhu, H; Lohman, Kk; Rudock, Me; Heckbert, Sr; Smith, Nl; Wiggins, Kl; Shriner, D; Veldre, G; Viigimaa, M; Kinra, S; Prabhakaran, D; Tripathy, V; Langefeld, Cd; Rosengren, A; Thelle, Ds; Corsi, Am; Singleton, A; Forrester, T; Hilton, G; Mckenzie, Ca; Salako, T; Iwai, N; Kita, Y; Ogihara, T; Ohkubo, T; Okamura, T; Ueshima, H; Umemura, S; Eyheramendy, S; Meitinger, T; Wichmann, He; Cho, Ys; Kim, Hl; Lee, Jy; Scott, J; Sehmi, J; Zhang, W; Hedblad, B; Nilsson, P; Smith, Gd; Wong, A; Narisu, N; Stancáková, A; Raffel, Lj; Yao, J; Kathiresan, S; O'Donnell, C; Schwartz, Sm; Ikram, Ma; Longstreth WT Jr,; Seshadri, S; Shrine, Nr; Wain, Lv; Morken, Ma; Swift, Aj; Laitinen, J; Prokopenko, I; Zitting, P; Cooper, Ja; Humphries, S; Danesh, J; Rasheed, A; Oel, A; Hamsten, A; Watkins, H; Bakker, Sj; van Gilst WH,; Janipalli, Cs; Mani, Kr; Yajnik, Cs; Hofman, A; Mattace Raso FU,; Oostra, Ba; Demirkan, A; Isaacs, A; Rivadeneira, F; Lakatta, Eg; Orru, M; Scuteri, A; Ala Korpela, M; Kangas, Aj; Lyytikäinen, Lp; Soininen, P; Tukiainen, T; Würz, P; Ong, Rt; Dörr, M; Kroemer, Hk; Völker, U; Völzke, H; Galan, P; Hercberg, S; Lathrop, M; Zelenika, D; Deloukas, P; Mangino, M; Spector, Td; Zhai, G; Meschia, Jf; Nalls, Ma; Sharma, P; Terzic, J; Kumar, Mj; Denniff, M; Zukowska Szczechowska, E; Wagenknecht, Le; Fowkes, Fg; Charchar, Fj; Schwarz, Pe; Hayward, C; Guo, X; Bots, Ml; Brand, E; Samani, Nj; Polasek, O; Talmud, Pj; Nyberg, F; Kuh, D; Laan, M; Hveem, K; Palmer, Lj; van der Schouw YT,; Casas, Jp; Mohlke, Kl; Vineis, Paolo; Raitakari, O; Wong, Ty; Tai, Es; Laakso, M; Rao, Dc; Harris, Tb; Morris, Rw; Dominiczak, Af; Kivimaki, M; Marmot, Mg; Miki, T; Saleheen, D; Chandak, Gr; Coresh, J; Navis, G; Salomaa, V; Han, Bg; Kooner, Js; Melander, O; Ridker, Pm; Bandinelli, S; Gyllensten, Ub; Wright, Af; Wilson, Jf; Ferrucci, L; Farrall, M; Tuomilehto, J; Pramstaller, Pp; Elosua, R; Soranzo, N; Sijbrands, Ej; Altshuler, D; Loos, Rj; Shuldiner, Ar; Gieger, C; Meneton, P; Uitterlinden, Ag; Wareham, Nj; Gudnason, V; Rettig, R; Uda, M; Strachan, Dp; Witteman, Jc; Hartikainen, Al; Beckmann, Js; Boerwinkle, E; Boehnke, M; Larson, Mg; Järvelin, Mr; Psaty, Bm; Abecasis, Gr; Elliott, P; van Duijn, C; Newton Cheh, C.

doi:10.1093/hmg/ddr092

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