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7 results on '"Ehret, Georg B"'

1. Analysis of putative cis-regulatory elements regulating blood pressure variation

Author

Nandakumar, Priyanka, Lee, Dongwon, Hoffmann, Thomas J, Ehret, Georg B, Arking, Dan, Ranatunga, Dilrini, Li, Man, Grove, Megan L, Boerwinkle, Eric, Schaefer, Catherine, Kwok, Pui-Yan, Iribarren, Carlos, Risch, Neil, and Chakravarti, Aravinda

Subjects
Biotechnology, Genetics, Aging, Cardiovascular, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Aorta, Atherosclerosis, Blood Pressure, Chromatin, Gene Expression Regulation, Genome-Wide Association Study, Heart, Humans, Intracellular Signaling Peptides and Proteins, Kidney, Membrane Proteins, Quantitative Trait Loci, Regulatory Sequences, Nucleic Acid, Tibial Arteries, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Hundreds of loci have been associated with blood pressure (BP) traits from many genome-wide association studies. We identified an enrichment of these loci in aorta and tibial artery expression quantitative trait loci in our previous work in ~100 000 Genetic Epidemiology Research on Aging study participants. In the present study, we sought to fine-map known loci and identify novel genes by determining putative regulatory regions for these and other tissues relevant to BP. We constructed maps of putative cis-regulatory elements (CREs) using publicly available open chromatin data for the heart, aorta and tibial arteries, and multiple kidney cell types. Variants within these regions may be evaluated quantitatively for their tissue- or cell-type-specific regulatory impact using deltaSVM functional scores, as described in our previous work. We aggregate variants within these putative CREs within 50 Kb of the start or end of 'expressed' genes in these tissues or cell types using public expression data and use deltaSVM scores as weights in the group-wise sequence kernel association test to identify candidates. We test for association with both BP traits and expression within these tissues or cell types of interest and identify the candidates MTHFR, C10orf32, CSK, NOV, ULK4, SDCCAG8, SCAMP5, RPP25, HDGFRP3, VPS37B and PPCDC. Additionally, we examined two known QT interval genes, SCN5A and NOS1AP, in the Atherosclerosis Risk in Communities Study, as a positive control, and observed the expected heart-specific effect. Thus, our method identifies variants and genes for further functional testing using tissue- or cell-type-specific putative regulatory information.

Published
2020

2. Loci influencing blood pressure identified using a cardiovascular gene-centric array

Author

Ganesh, Santhi K, Tragante, Vinicius, Guo, Wei, Guo, Yiran, Lanktree, Matthew B, Smith, Erin N, Johnson, Toby, Castillo, Berta Almoguera, Barnard, John, Baumert, Jens, Chang, Yen-Pei Christy, Elbers, Clara C, Farrall, Martin, Fischer, Mary E, Franceschini, Nora, Gaunt, Tom R, Gho, Johannes MIH, Gieger, Christian, Gong, Yan, Isaacs, Aaron, Kleber, Marcus E, Leach, Irene Mateo, McDonough, Caitrin W, Meijs, Matthijs FL, Mellander, Olle, Molony, Cliona M, Nolte, Ilja M, Padmanabhan, Sandosh, Price, Tom S, Rajagopalan, Ramakrishnan, Shaffer, Jonathan, Shah, Sonia, Shen, Haiqing, Soranzo, Nicole, van der Most, Peter J, Van Iperen, Erik PA, Van Setten, Jessic A, Vonk, Judith M, Zhang, Li, Beitelshees, Amber L, Berenson, Gerald S, Bhatt, Deepak L, Boer, Jolanda MA, Boerwinkle, Eric, Burkley, Ben, Burt, Amber, Chakravarti, Aravinda, Chen, Wei, Cooper-DeHoff, Rhonda M, Curtis, Sean P, Dreisbach, Albert, Duggan, David, Ehret, Georg B, Fabsitz, Richard R, Fornage, Myriam, Fox, Ervin, Furlong, Clement E, Gansevoort, Ron T, Hofker, Marten H, Hovingh, G Kees, Kirkland, Susan A, Kottke-Marchant, Kandice, Kutlar, Abdullah, LaCroix, Andrea Z, Langaee, Taimour Y, Li, Yun R, Lin, Honghuang, Liu, Kiang, Maiwald, Steffi, Malik, Rainer, Murugesan, Gurunathan, Newton-Cheh, Christopher, O'Connell, Jeffery R, Onland-Moret, N Charlotte, Ouwehand, Willem H, Palmas, Walter, Penninx, Brenda W, Pepine, Carl J, Pettinger, Mary, Polak, Joseph F, Ramachandran, Vasan S, Ranchalis, Jane, Redline, Susan, Ridker, Paul M, Rose, Lynda M, Scharnag, Hubert, Schork, Nicholas J, Shimbo, Daichi, Shuldiner, Alan R, Srinivasan, Sathanur R, Stolk, Ronald P, Taylor, Herman A, Thorand, Barbara, Trip, Mieke D, van Duijn, Cornelia M, Verschuren, W Monique, Wijmenga, Cisca, Winkelmann, Bernhard R, Wyatt, Sharon, and Young, J Hunter

Subjects
Hypertension, Heart Disease, Human Genome, Genetics, Clinical Research, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Blood Pressure, Cardiovascular Diseases, Chromosome Mapping, Cohort Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, White People, CARDIOGRAM, METASTROKE, LifeLines Cohort Study, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.

Published
2013

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

Author

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 LR, Taylor, Herman A, Caulfield, Mark J, Ehret, Georg B, Johnson, Toby, Studies, The International Consortium for Blood Pressure Genome-wide Association, 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, DG, 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, and Onland-Moret, N Charlotte

Subjects
Biological Sciences, Genetics, Clinical Research, Hypertension, Human Genome, Minority Health, Health Disparities, Cardiovascular, Prevention, Adult, Black or African American, Aged, Blood Pressure, Cohort Studies, Diastole, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Systole, White People, International Consortium for Blood Pressure Genome-wide Association Studies, Medical and Health Sciences, Genetics & Heredity
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.

Published
2011

4. Positional identification of variants of Adamts16 linked to inherited hypertension

Author

Joe, Bina, Saad, Yasser, Lee, Norman H., Frank, Bryan C., Achinike, Ovokeraye H., Luu, Truong V., Gopalakrishnan, Kathirvel, Toland, Edward J., Farms, Phyllis, Yerga-Woolwine, Shane, Manickavasagam, Ezhilarasi, Rapp, John P., Garrett, Michael R., Coe, David, Apte, Suneel S., Rankinen, Tuomo, Pérusse, Louis, Ehret, Georg B., Ganesh, Santhi K., Cooper, Richard S., O'Connor, Ashley, Rice, Treva, Weder, Alan B., Chakravarti, Aravinda, Rao, Dabeeru C., and Bouchard, Claude

Published
2009

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

Author

Spector, Tim D., Rotimi, Charles N., Hedblad, Bo, Brand, Eva, Day, Ian N. M., Kita, Yoshikuni, Chandak, Giriraj R., Tomaszewski, Maciej, Wong, Andrew, Ogihara, Toshio, Salomaa, Veikko, Igl, Wilmar, Laitinen, Jaana, Olden, Matthias, Okamura, Tomonori, Peltonen, Leena, Witteman, Jacqueline C. M., Wichmann, H-erich, Palmer, Lyle J., Boerwinkle, Eric, Talmud, Philippa J., Tabara, Yasuharu, Platou, Carl G. P., Gyllensten, Ulf B., Meneton, Pierre, Dominiczak, Anna F., Frayling, Timothy M., Groop, Leif, Smith, Albert V., Jackson, Anne U., Kutlar, Abdullah, Heath, Simon, Voight, Benjamin F., Meitinger, Thomas, Stringham, Heather M., Gaunt, Tom R., Islam, Muhammad, Tai, E. Shyong, Hofman, Albert, Lohman, Kurt K., Rotter, Jerome I., Hoffman Bolton, Judith A., Schouw, Yvonne T., Raffel, Leslie J., Lawrence, Robert W., Rudock, Megan E., Scuteri, Angelo, Peden, John F., Eyheramendy, Susana, Aspelund, Thor, Adair, Linda S., Demirkan, Ayse, Staessen, Jan A., Glazer, Nicole L., Launer, Lenore, Ganesh, Santhi, Hirschorn, Joel N., Seshadri, Sudha, Sjo&#776, gren, Marketa, Musani, Solomon K., Verwoert, Germaine C., Umemura, Satoshi, Bis, Joshua C., Dreisbach, Albert W., Keating, Brendan J., Ala-korpela, Mika, Hartikainen, Anna-liisa, Galan, Pilar, Strachan, David P., Hadley, David, Prokopenko, Inga, Young, J. Hunter, Ehret, Georg B., Prabhakaran, Dorairajan, Scott, Laura J., Mosley, Thomas H., Viikari, Jorma, Ohkubo, Takayoshi, Wiggins, Kerri L., Emilsson, Valur, Salako, Tunde, Vo&#776, lker, Uwe, Bornstein, Stefan R., lzke, Henry, Dries, Daniel L., Sharma, Pankaj, Ueshima, Hirotsugu, Wright, Alan F., Lee, Nanette R., Loos, Ruth J. F., Lawlor, Debbie A., Kathiresan, Sekar, Cho, Yoon Shin, Luan, Jian An, Jafar, Tazeen H., Bakker, Stephan J. L., Altshuler, David, Arking, Dan E., Tayo, Bamidele O., Smith, George Davey, Liu, Kiang, Taylor, Herman A., Parsa, Afshin, Mattace-raso, Francesco U. S., Wild, Sarah H., Guo, Xiuqing, Shuldiner, Alan R., Zhang, Weihua, Zhang, Feng, Harris, Tamara B., Kuusisto, Johanna, Zukowska-szczechowska, Ewa, Nyberg, Fredrik, Vineis, Paolo, Dahgam, Santosh, Hayward, Caroline, Hicks, Andrew A., Kuh, Diana, Shriner, Daniel, Taylor, Andrew, Mckenzie, Colin A., Wang, Thomas J., Steinle, Nanette I., Elosua, Roberto, Sim, Xueling, Kang, Sun J., Rivadeneira, Fernando, Palmen, Jutta, Cooper, Matthew N., Lyon, Helen N., Levy, Daniel, Swift, Amy J., Raitakari, Olli, Lyytika&#776, inen, Leo-pekka, Saleheen, Danish, Rudan, Igor, Schwarz, Peter E. H., Kooner, Jaspal S., Smith, Nicholas L., Matullo, Giuseppe, Barroso, Ine&#770, s, O Connell, Jeffrey R., Hunt, Steven C., Hernandez, Dena, Erdmann, Jeanette, Wu&#776, rz, Peter, Forrester, Terrence, Burton, Paul R., Ongen, Halit, Bandinelli, Stefania, Thelle, Dag S., Sehmi, Joban S., O Reilly, Paul F., Braund, Peter S., Danesh, John, Wyatt, Sharon B., Parker, Alex N., Polak, Josef F., Collins, Rory, Zhao, Jing Hua, Shi, Gang, Dehghan, Abbas, Rosengren, Annika, Whincup, Peter H., Duijn, Cornelia M., Hwang, Shih-jen, Ridker, Paul M., Chakravarti, Aravinda, Uda, Manuela, Tanaka, Toshiko, Pramstaller, Peter P., Morken, Mario A., Soininen, Pasi, Abecasis, Gonc&#807, alo R., Zhai, Guangju, Curb, J. David, Ferrucci, Luigi, Doumatey, Ayo P., Fox, Ervin R., Bergman, Richard N., Johnson, Toby, Larson, Martin G., Snieder, Harold, Morris, Richard W., Onland-moret, N. Charlotte, Johnson, Andrew D., Narisu, Narisu, Samani, Nilesh J., Pihur, Vasyl, Chaturvedi, Nish, Melander, Olle, Hamsten, Anders, Charchar, Fadi J., Ludwig, Barbara, Kim, Hyung-lae, Bergmann, Sven, Nalls, Michael A., Milaneschi, Yuri, Palmer, Nicholette D., Alexander, Myriam, Townsend, Raymond R., Caulfield, Mark J., Hilton, Gina, Tuomilehto, Jaakko, Lee, Jong-young, Perola, Markus, Grobbee, Diederick E., Longstreth, Will T., Munroe, Patricia B., Uitterlinden, Andre G., Iwai, Naoharu, Adeyemo, Adebowale, Cooper, Richard S., Mcardle, Wendy L., Sun, Yan V., Sijbrands, Eric J. G., Fabsitz, Richard R., Nguyen, Khanh-dung Hoang, Martin, Lisa W., Wareham, Nicholas J., Brown, Morris J., Wang, Xiaoling, Kuznetsova, Tatiana, Rao, Dabeeru C., Org, Elin, Gilst, Wiek H., Orru, Marco, Oostra, Ben A., Howard, Philip, Wagenknecht, Lynne E., Meschia, James F., Mooser, Vincent, Lehtima&#776, ki, Terho, Wong, Tien Y., Langefeld, Carl D., Bragg-gresham, Jennifer L., Bochud, Murielle, Arora, Pankaj, Kivimaki, Mika, Seielstad, Mark, O Donnell, Chris, Chasman, Daniel I., Farrall, Martin, Polasek, Ozren, Fava, Cristiano, Vitart, Veronique, Mani, K. Radha, Uiterwaal, Cuno S. P. M., Chang, Yen-pei C., Zhu, Haidong, Morrison, Alanna C., Bonnycastle, Lori L., Najjar, Samer, Vollenweider, Peter, Eaton, Charles B., Singleton, Andrew, Teumer, Alexander, Deloukas, Panos, Campbell, Harry, Terzic, Janos, Aulchenko, Yurii, Farlow, Deborah N., Psaty, Bruce M., Beckmann, Jacques S., Scott, James, Tobin, Martin D., Kao, Wen Hong Linda, Harst, Pim, Amin, Najaf, Zitting, Paavo, Pattaro, Cristian, Casas, Juan P., Ikram, M. Arfan, Coresh, Josef, Hingorani, Aroon D., Kulkarni, Smita R., Shrine, Nick R. G., Yao, Jie, Fowkes, F. Gerald R., Clarke, Robert, Gra&#776, ssler, Ju&#776, rgen, Hercberg, Serge, Wain, Louise V., Redline, Susan, Isaacs, Aaron, Hopewell, Jemma C., Lathrop, Mark, Vinay, D. G., Marmot, Michael G., Laan, Maris, Rasheed, Asif, So&#771, ber, Siim, Vartiainen, Erkki, Han, Bok-ghee, Rettig, Rainer, Kinra, Sanjay, Artigas, Maria Soler, Veldre, Gudrun, Navis, Gerjan, Shaw-hawkins, Sue, Franceschini, Nora, Lucas, Gavin, Penman, Alan D., Ong, Rick Twee-hee, Mohlke, Karen L., Beilby, John P., Zhu, Xiaofeng, Bots, Michiel L., Chen, Ming-huei, Denniff, Matthew, Brand, Stefan-martin, Kangas, Antti J., Hveem, Kristian, Chambers, John C., Tukiainen, Taru, Boehnke, Michael, Ramachandran, Vasan S., Connell, John M., Collins, Francis S., Khaw, Kay-tee, Nilsson, Peter, Wilson, James F., Yajnik, Chittaranjan S., Guarrera, Simonetta, Gieger, Christian, Elliott, Paul, Plump, Andrew, Ricceri, Fulvio, Tzoulaki, Ioanna, Garcia, Melissa, Ka&#776, ho&#776, nen, Mika, Laakso, Markku, Kumari, Meena, Stanca&#769, kova&#769, Alena, Corsi, Anna Maria, Soranzo, Nicole, Kettunen, Johannes, Gudnason, Vilmundur, Kardia, Sharon L. R., Hardy, Rebecca, Lakatta, Edward G., Goel, Anuj, Liu, Yongmei, Dong, Yanbin, Humphries, Steve E., Rice, Kenneth M., Newton-cheh, Christopher, Ko&#776, ttgen, Anna, Viigimaa, Margus, Tripathy, Vikal, Mangino, Massimo, Janipalli, Charles S., Heckbert, Susan R., Palmas, Walter, Watkins, Hugh, Do&#776, rr, Marcus, Kroemer, Heyo K., Weder, Alan B., Wu, Ying, Schwartz, Steven M., Miki, Tetsuro, Zelenika, Diana, Cooper, Jackie A., Kumar, M. J. Kranthi, International Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS), Ja&#776, rvelin, Marjo-riitt, EchoGen consortium, CARDIoGRAM consortium, CKDGen consortium, Charge-hf, Consortium, KidneyGen consortium, Medical Research Council (MRC), Kuznetsova, Tatiana, Staessen, Jan A, Pediatrics, Ehret, Georg Benedikt, International Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS), CARDIoGRAM consortium, CKDGen consortium, KidneyGen consortium, EchoGen consortium, CHARGE-HF consortium, Morrison, Alanna C [0000-0001-6381-4296], Ramachandran, Vasan S [0000-0001-7357-5970], Adeyemo, Adebowale [0000-0002-3105-3231], Martin, Lisa W [0000-0003-4352-0914], Caulfield, Mark J [0000-0001-9295-3594], Levy, Daniel [0000-0003-1843-8724], Apollo - University of Cambridge Repository, Epidemiologie, and RS: CARIM School for Cardiovascular Diseases

Subjects
Male, Candidate gene, Blood pressure, GWAS, genetic variant, African Americans, Genome-wide association study, Blood Pressure, 030204 cardiovascular system & hematology, Cardiovascular, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, Diastole, 2.1 Biological and endogenous factors, International Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS), European Continental Ancestry Group/genetics, Aetiology, International HapMap Project, International Consortium for Blood Pressure Genome-wide Association Studies, Genetics (clinical), ddc:616, Genetics, Genetics & Heredity, 0303 health sciences, Association Studies Articles, Single Nucleotide, General Medicine, 11 Medical And Health Sciences, Biological Sciences, Middle Aged, 3. Good health, Phenotype, Hypertension, Female, Adult, Genotype, Systole, European Continental Ancestry Group, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, White People, genome-wide association, hypertension prevalence, receptor, disease, family, loci, vasculature, awareness, traits, design, 03 medical and health sciences, Clinical Research, Genetic variation, Humans, Genetic variability, Polymorphism, Hypertension/epidemiology/genetics, Molecular Biology, 030304 developmental biology, Genetic association, Aged, African Americans/genetics, Human Genome, 06 Biological Sciences, Black or African American, Genetic Loci, Genome-Wide Association Study, Hypertension/epidemiology, Hypertension/genetics, Imputation (genetics)
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. ispartof: HUMAN MOLECULAR GENETICS vol:20 issue:11 pages:2273-2284 ispartof: location:England status: published

Published
2011
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7. Positional identification of variants of Adamts16 linked to inherited hypertension.

Author

Joe, Bina, Saad, Yasser, Dhindaw, Seema, Lee, Norman H., Frank, Bryan C., Achinike, Ovokeraye H., Luu, Truong V., Gopalakrishnan, Kathirvel, Toland, Edward J., Farms, Phyllis, Yerga-Woolwine, Shane, Manickavasagam, Ezhilarasi, Rapp, John P., Garrett, Michael R., Coe, David, Apte, Suneel S., Rankinen, Tuomo, Pérusse, Louis, Ehret, Georg B., and Ganesh, Santhi K.

Published
2011
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