Search

Your search keyword '"Krieger J.E."' showing total 95 results
Start Over Author "Krieger J.E."
95 results on '"Krieger J.E."'

1. The Ag-195 (C®G) mutation in hereditary persistence of fetal hemoglobin is not associated with activation of a reporter gene in vitro

Author

Schreiber R., Gonçalves M.S., Junqueira M.L., Saad S.T.O., Krieger J.E., and Costa F.F.

Subjects
fetal hemoglobin, hereditary persistence of fetal hemoglobin, HPFH, transient expression, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Hereditary persistence of fetal hemoglobin is an uncommon, benign disorder in which the expression of gamma-globin genes persists into adult life. Several point mutations have been associated with the increased gamma-globin gene promoter activity. We evaluated the -195 (C->G) mutation by a functional in vitro assay based on the luciferase reporter gene system. The results indicated that the increased promoter activity observed in vivo could not be reproduced in vitro under the conditions employed, suggesting that other factors may be involved in the overexpression of the gamma-globin gene containing the -195 (C->G) mutation. Furthermore, this is the first time that the -195 (C->G) mutation of the Agamma-globin gene has been evaluated by in vitro gene expression.

Published
2001

2. Characterization of six rat strains (Rattus norvegicus) by mitochondrial DNA restriction fragment length polymorphism

Author

Hilsdorf A.W. and Krieger J.E.

Subjects
restriction fragment length polymorphism (RFLP), Rattus norvegicus, mtDNA, laboratory rats, genetic monitoring, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Restriction fragment length polymorphism (RFLP) was used to examine the extent of mtDNA polymorphism among six strains of rats (Rattus norvegicus) - Wistar, Wistar Munich, Brown Norway, Wistar Kyoto, SHR and SHR-SP. A survey of 26 restriction enzymes has revealed a low level of genetic divergence among strains. The sites of cleavage by EcoRI, NcoI and XmnI were shown to be polymorphic. The use of these three enzymes allows the 6 strains to be classified into 4 haplotypes and identifies specific markers for each one. The percentage of sequence divergence among all pairs of haplotypes ranged from 0.035 to 0.33%, which is the result of a severe population constriction undergone by the strains. These haplotypes are easily demonstrable and therefore RFLP analysis can be employed for genetic monitoring of rats within animal facilities or among different laboratories.

Published
1999

5. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

Author

de las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F., Schwander, Karen, Bentley, Amy R., Brown, Michael R., Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I., Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P., Horimoto, A.R.V.R., Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K., Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Tayo, Bamidele O., Vojinovic, Dina, Warren, Helen R., Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B., Weiss, Stefan, Yanek, Lisa R., Amin, Najaf, Arking, Dan E., Arnett, Donna K., Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P., Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H. Janaka, de Vries, Paul S., Eiriksdottir, Gudny, Faul, Jessica D., Fisher, Virginia, Forrester, Terrence, Fox, Ervin F., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M. Arfan, Irvin, Marguerite R., Kähönen, Mika, Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon-Puay, Komulainen, Pirjo, Kraja, Aldi T., Krieger, J.E., Langefeld, Carl D., Li, Yize, Liang, Jingjing, Liewald, David C. M., Liu, Ching-Ti, Liu, Jianjun, Lohman, Kurt K., Mägi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mook-Kanamori, Dennis O., Nalls, Mike A., Nelson, Christopher P., Norris, Jill M., O’Connell, Jeff, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmer, Nicholette D., Pedersen, Nancy L., Perls, Thomas, Peters, Annette, Petersmann, Astrid, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Raffel, Leslie J., Rice, Treva K., Rotter, Jerome I., Rudan, Igor, Rueda-Ochoa, Oscar-Leonel, Sabanayagam, Charumathi, Salako, Babatunde L., Schreiner, Pamela J., Shikany, James M., Sidney, Stephen S., Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Swertz, Morris A., Teumer, Alexander, Tham, Yih Chung, Uitterlinden, André G., Vaidya, Dhananjay, van der Ende, M. Yldau, Waldenberger, Melanie, Wang, Lihua, Wang, Ya-Xing, Wei, Wen-Bin, Weir, David R., Wen, Wanqing, Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Bowden, Donald W., Deary, Ian J., Dörr, Marcus, Esko, Tõnu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kammerer, Candace M., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K. E., Marques-Vidal, Pedro, Penninx, Brenda W. J. H., Samani, Nilesh J., van der Harst, Pim, Wagenknecht, Lynne E., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Cooper, Richard S., Correa, Adolfo, Evans, Michele K., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Kritchevsky, Stephen B., Levy, Daniel, Palmas, Walter R., Pereira, A.C., Province, Michael M., Psaty, Bruce M., Ridker, Paul M., Rotimi, Charles N., Tai, E. Shyong, van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Rice, Kenneth, Gauderman, W. James, Morrison, Alanna C., North, Kari E., Kardia, Sharon L. R., Caulfield, Mark J., Elliott, Paul, Munroe, Patricia B., Franks, Paul W., Rao, Dabeeru C., Fornage, Myriam, de las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F., Schwander, Karen, Bentley, Amy R., Brown, Michael R., Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I., Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P., Horimoto, A.R.V.R., Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K., Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Tayo, Bamidele O., Vojinovic, Dina, Warren, Helen R., Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B., Weiss, Stefan, Yanek, Lisa R., Amin, Najaf, Arking, Dan E., Arnett, Donna K., Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P., Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H. Janaka, de Vries, Paul S., Eiriksdottir, Gudny, Faul, Jessica D., Fisher, Virginia, Forrester, Terrence, Fox, Ervin F., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M. Arfan, Irvin, Marguerite R., Kähönen, Mika, Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon-Puay, Komulainen, Pirjo, Kraja, Aldi T., Krieger, J.E., Langefeld, Carl D., Li, Yize, Liang, Jingjing, Liewald, David C. M., Liu, Ching-Ti, Liu, Jianjun, Lohman, Kurt K., Mägi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mook-Kanamori, Dennis O., Nalls, Mike A., Nelson, Christopher P., Norris, Jill M., O’Connell, Jeff, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmer, Nicholette D., Pedersen, Nancy L., Perls, Thomas, Peters, Annette, Petersmann, Astrid, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Raffel, Leslie J., Rice, Treva K., Rotter, Jerome I., Rudan, Igor, Rueda-Ochoa, Oscar-Leonel, Sabanayagam, Charumathi, Salako, Babatunde L., Schreiner, Pamela J., Shikany, James M., Sidney, Stephen S., Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Swertz, Morris A., Teumer, Alexander, Tham, Yih Chung, Uitterlinden, André G., Vaidya, Dhananjay, van der Ende, M. Yldau, Waldenberger, Melanie, Wang, Lihua, Wang, Ya-Xing, Wei, Wen-Bin, Weir, David R., Wen, Wanqing, Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Bowden, Donald W., Deary, Ian J., Dörr, Marcus, Esko, Tõnu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kammerer, Candace M., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K. E., Marques-Vidal, Pedro, Penninx, Brenda W. J. H., Samani, Nilesh J., van der Harst, Pim, Wagenknecht, Lynne E., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Cooper, Richard S., Correa, Adolfo, Evans, Michele K., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Kritchevsky, Stephen B., Levy, Daniel, Palmas, Walter R., Pereira, A.C., Province, Michael M., Psaty, Bruce M., Ridker, Paul M., Rotimi, Charles N., Tai, E. Shyong, van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Rice, Kenneth, Gauderman, W. James, Morrison, Alanna C., North, Kari E., Kardia, Sharon L. R., Caulfield, Mark J., Elliott, Paul, Munroe, Patricia B., Franks, Paul W., Rao, Dabeeru C., and Fornage, Myriam

Abstract

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.

Published
2021
Full Text
View/download PDF

7. The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Author

Ferreira, J.C.B., Bacurau, A.V., Evangelista, F.S., Coelho, M.A., Oliveira, E.M., Casarini, D.E., Krieger, J.E., and Brum, P.C.

Subjects
Renin-angiotensin system -- Research, Angiotensin II receptor blockers -- Research, Heart failure -- Research, Cardiovascular research, Biological sciences
Abstract

Sympathetic hyperactivity (SH) and renin angiotensin system (RAS) activation are commonly associated with heart failure (HF), even though the relative contribution of these factors to the cardiac derangement is less understood. The role of SH on RAS components and its consequences for the HF were investigated in mice lacking U2A and OL2c adrenoceptor knockout ([[alpha].sub.2A]/[[alpha].sub.2C]ARKO) that present SH with evidence of HF by 7 mo of age. Cardiac and systemic RAS components and plasma norepinephrine (PN) levels were evaluated in male adult mice at 3 and 7 mo of age. In addition, cardiac morphometric analysis, collagen content, exercise tolerance, and hemodynamic assessments were made. At 3 mo, [[alpha].sub.2A]/[[alpha].sub.2C]ARKO mice showed no signs of HF, while displaying elevated PN, activation of local and systemic RAS components, and increased cardiomyocyte width (16%) compared with wild-type mice (WT). In contrast, at 7 too, [[alpha].sub.2A]/[[alpha].sub.2C] ARKO mice presented clear signs of HF accompanied only by cardiac activation of angiotensinogen and ANG II levels and increased collagen content (twofold). Consistent with this local activation of RAS, 8 wk of ANG II [AT.sub.1] receptor blocker treatment restored cardiac structure and function comparable to the WT. Collectively, these data provide direct evidence that cardiac RAS activation plays a major role underlying the structural and functional abnormalities associated with a genetic SH-induced HF in mice. sympathetic nervous system; AT1 receptor blocker; [[alpha].sub.2a]/[[alpha].sub.2c] adrenergic knockout mice

Published
2008

8. Anabolic steroids induce cardiac renin-angiotensin system and impair the beneficial effects of aerobic training in rats

Author

Rocha, F.L., Carmo, E.C., Roque, F.R., Hashimoto, N.Y., Rossoni, L.V., Frimm, C., Aneas, I., Negrao, C.E., Krieger, J.E., and Oliveira, E.M.

Subjects
Aerobic exercises -- Health aspects, Aerobic exercises -- Research, Anabolic steroids -- Dosage and administration, Anabolic steroids -- Research, Renin-angiotensin system -- Health aspects, Renin-angiotensin system -- Research, Biological sciences
Abstract

We evaluated the effects of swimming and anabolic steroids (AS) on ventricular function, collagen synthesis, and the local renin-angiotensin system in rats. Male Wistar rats were randomized into control (C), steroid (S; nandrolone decanoate; 5 mg/kg sc, 2x/wk), steroid + losartan (SL; 20 mg x [kg.sup.-1] x [day.sup.-1]), trained (T), trained + steroid (T+S), and trained + steroid + losartan (T+SL; n = 14/group) groups. Swimming was performed 5 times/wk for 10 wk. Serum testosterone increased in S and T+S. Resting heart rate was lower in T and T+S. Percent change in left ventricular (LV) weight-to-body weight ratio increased in S, T, and T+S. LV systolic pressure declined in S and T+S. LV contractility increased in T (P < 0.05). LV relaxation increased in T (P < 0.05). It was significantly lower in T+S compared with C. Collagen volumetric fraction (CVF) and hydroxyproline were higher in S and T+S than in C and T (P < 0.05), and the CVF and LV hypertrophy were prevented by losartan treatment. LV-ANG I-converting enzyme activity increased (28%) in the S group (33%), and type III collagen synthesis increased (56%) in T+S but not in T group. A positive correlation existed between LV-ANG I-converting enzyme activity and collagen type III expression ([r.sup.2] = 0.88; P < 0.05, for all groups). The ANG II and angiotensin type 1a receptor expression increased in the S and T+S groups but not in T group. Supraphysiological doses of AS exacerbated the cardiac hypertrophy in exercise-trained rats. Exercise training associated with AS induces maladaptive remodeling and further deterioration in cardiac performance. Exercise training associated with AS causes loss of the beneficial effects in LV function induced by exercising. These results suggest that aerobic exercise plus AS increases cardiac collagen content associated with activation of the local renin-angiotensin system. cardiac hypertrophy; collagen; renin-angiotensin system; ventricular function

Published
2007

13. Molecular aspects of Homozygous Familial Hypercholesterolemia in Iberoamerican Countries

Author

Alves, A.C., Alonso, R., Cuevas, A., Medeiros, A.M., Pereira, A.C., Jannes, C.E., Krieger, J.E., Arroyo, R., Schreier, L., Corral, P., Bañares, V., Araujo, G.M., Asenjo, S., Stoll, M., Dell'Oca, N., Reyes, X., Ressia, A., Campo, R., Merchan, A., Magaña-Torres Teresa, M., Vasques-Cardenas, A., Mata, N.P., Santos, R.D., and Bourbon, M.

Subjects
Homozygous Familial Hypercholesterolemia, HoFH Diagnosis, Molecular Characteristics, Familial Hypercholesterolemia, Iberoamerican Countries, Doenças Cardio e Cérebro-vasculares
Abstract

Homozygous Familial Hypercholesterolemia (HoFH) is a rare disorder, affecting 1 in 300,000 to 1,000,000 people in the general population. The Iberoamerican FH (IBAFH) network was constituted in 2013 with the main objectives to promote awareness and education on FH, and to improve and promote early diagnosis and treatment of the disorder in the network countries. In 2018, there are 8 countries (Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain and Uruguay) belonging to the network representing 75% of region’s population. It is estimated that there are 600 to 1,800 HoFH in the Ibero-America, most of them not diagnosed and/or not treated adequately. The Iberoamerican community has an estimated population of 640 million inhabitants. The objective of this work is to describe molecular characteristics of HoFH diagnosis in Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain, and Uruguay. N/A

Published
2019

14. A luciferase-engineered cell line for study of cAMP regulation in endothelial cells

Author

Xavier-neto, J., Pereira, A.C., Motoyama, A.H., and Krieger, J.E.

Subjects
Adenylic acid -- Physiological aspects, Rats -- Physiological aspects, Endothelium -- Cytology, Cells -- Physiological aspects, Biological sciences
Abstract

A study was conducted to characterize a sensitive adenosine 3',5'-cyclic monophosphate (cAMP) responsive endothelial cell line. The cell lien was determined through a stable transfection of a luciferase enhancer trap into the aortic endothelial cells of rabbits. Results indicated that a cAMP-responsive endothelial cell line supporting a luciferase reporter gene could be utilized to analyze patterns of gene activation by cAMP and by Ca2+ after complex stimuli.

Published
1998

15. Angiotensin I-converting enzyme activity in tubular fluid along the rat nephron

Author

Casarini, D.E., Boim, M.A., Stella, R.C.R., Krieger-Azzolini, M.H., Krieger, J.E., and Schor, N.

Subjects
Kidney tubules -- Physiological aspects, Angiotensin converting enzyme -- Physiological aspects, Kidneys -- Physiological aspects, Biological sciences
Abstract

Tubular fluids collected from rat nephron and urine were analyzed to determine the activity of the angiotensin-converting enzyme (ACE) or kinninase II on kidney function. Analysis of rat renal tubular fluid based on micropuncture techniques indicated the presence of ACE activity in the initial and terminal parts of the nephron. However, ACE activity decreased in the early proximal tubule and late distal tubule. Furthermore, ACE activity was modified along the distal nephron of rat kidneys.

Published
1997

16. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Author

Noordam, R. (Raymond), Bos, M.M. (Maxime M.), Wang, H. (Heming), Winkler, T.W. (Thomas W.), Bentley, A.R. (Amy), Kilpeläinen, T.O. (Tuomas O.), Vries, P.S. (Paul) de, Sung, Y.J. (Yun Ju), Schwander, K., Cade, B., Manning, A.K. (Alisa), Aschard, H. (Hugues), Brown, M.R., Chen, H. (Han), Franceschini, N. (Nora), Musani, S.K. (Solomon K.), Richard, M. (Melissa), Vojinović, D. (Dina), Aslibekyan, S. (Stella), Bartz, T.M. (Traci M.), de Las Fuentes, L. (Lisa), Feitosa, M.F. (Mary Furlan), Horimoto, A.R. (Andrea R.), Ilkov, M. (Marjan), Kho, M. (Minjung), Kraja, A. (Aldi), Li, C. (Changwei), Lim, E. (Elise), Liu, Y. (YongMei), Mook-Kanamori, D.O. (Dennis O.), Rankinen, T. (Tuomo), Tajuddin, S.M. (Salman M.), Spek, A. (Ashley) van der, Wang, Z. (Zhe), Marten, J. (Jonathan), Laville, V. (Vincent), Alver, M. (Maris), Evangelou, E. (Evangelos), Graff, M.E. (Maria E.), He, M. (Meian), Kuhnel, B. (Brigitte), Lyytikäinen, L.-P. (Leo-Pekka), Marques-Vidal, P. (Pedro), Nolte, I.M. (Ilja), Palmer, N.D. (Nicholette), Rauramaa, R. (Rainer), Shu, X.-O. (Xiao-Ou), Snieder, H. (Harold), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Adolfo, C. (Correa), Ballantyne, C. (Christie), Bielak, L.F. (Lawrence F.), Biermasz, N.R., Boerwinkle, E.A. (Eric), Dimou, N. (Niki), Eiriksdottir, G. (Gudny), Gao, C. (Chuan), Gharib, S.A. (Sina), Gottlieb, D.J. (Daniel J.), Haba-Rubio, J. (José), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heinzer, R. (Raphaël), Hixson, J.E. (James E.), Homuth, G. (Georg), Ikram, M.A. (Arfan), Komulainen, P. (Pirjo), Krieger, J.E. (José), Lee, J. (Jiwon), Liu, J. (Jingmin), Lohman, K.K. (Kurt K.), Luik, A.I. (Annemarie), Mägi, R. (Reedik), Martin, L.W. (Lisa), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Nalls, M.A. (Michael), O´Connell, J.R., Peters, A. (Annette), Peyser, P.A. (Patricia A.), Raitakari, O. (Olli), Reiner, A. (Alexander), Rensen, P.C.N. (Patrick), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Roenneberg, T., Rotter, J.I. (Jerome I.), Schreiner, P.J. (Pamela), Shikany, J. (James), Sidney, S.S. (Stephen S.), Sims, M. (Mario), Sitlani, C.M. (Colleen M.), Sofer, T. (Tamar), Strauch, K. (Konstantin), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Völzke, H. (Henry), Waldenberger, M. (Melanie), Wallance, R.B. (Robert B.), van Dijk, K.W. (Ko Willems), Yu, C. (Caizheng), Zonderman, A.B. (Alan B.), Becker, D.M. (Diane), Elliott, P. (Paul), Esko, T. (Tõnu), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), North, K.E. (Kari), Penninx, B.W.J.H. (Brenda), Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wu, T. (Tangchun), Xiang, Y.-B. (Yong-Bing), Zheng, W. (Wei), Arnett, D.K. (Donna), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Kardia, S.L.R. (Sharon), Kelly, T.N. (Tanika N.), Kritchevsky, S.B. (Stephen), Loos, R.J.F. (Ruth), Pereira, A. (A.), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rotimi, C. (Charles), Zhu, X. (Xiaofeng), Amin, N. (Najaf), Cupples, L.A. (L Adrienne), Fornage, M. (Myriam), Fox, E.F. (Ervin F.), Guo, X. (Xiuqing), Gauderman, W.J. (W James), Rice, K.M. (Kenneth), Kooperberg, C. (Charles), Munroe, P. (Patricia), Liu, C.-T. (Ching-Ti), Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Heemst, D. (Diana) van, Redline, S. (Susan), Noordam, R. (Raymond), Bos, M.M. (Maxime M.), Wang, H. (Heming), Winkler, T.W. (Thomas W.), Bentley, A.R. (Amy), Kilpeläinen, T.O. (Tuomas O.), Vries, P.S. (Paul) de, Sung, Y.J. (Yun Ju), Schwander, K., Cade, B., Manning, A.K. (Alisa), Aschard, H. (Hugues), Brown, M.R., Chen, H. (Han), Franceschini, N. (Nora), Musani, S.K. (Solomon K.), Richard, M. (Melissa), Vojinović, D. (Dina), Aslibekyan, S. (Stella), Bartz, T.M. (Traci M.), de Las Fuentes, L. (Lisa), Feitosa, M.F. (Mary Furlan), Horimoto, A.R. (Andrea R.), Ilkov, M. (Marjan), Kho, M. (Minjung), Kraja, A. (Aldi), Li, C. (Changwei), Lim, E. (Elise), Liu, Y. (YongMei), Mook-Kanamori, D.O. (Dennis O.), Rankinen, T. (Tuomo), Tajuddin, S.M. (Salman M.), Spek, A. (Ashley) van der, Wang, Z. (Zhe), Marten, J. (Jonathan), Laville, V. (Vincent), Alver, M. (Maris), Evangelou, E. (Evangelos), Graff, M.E. (Maria E.), He, M. (Meian), Kuhnel, B. (Brigitte), Lyytikäinen, L.-P. (Leo-Pekka), Marques-Vidal, P. (Pedro), Nolte, I.M. (Ilja), Palmer, N.D. (Nicholette), Rauramaa, R. (Rainer), Shu, X.-O. (Xiao-Ou), Snieder, H. (Harold), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Adolfo, C. (Correa), Ballantyne, C. (Christie), Bielak, L.F. (Lawrence F.), Biermasz, N.R., Boerwinkle, E.A. (Eric), Dimou, N. (Niki), Eiriksdottir, G. (Gudny), Gao, C. (Chuan), Gharib, S.A. (Sina), Gottlieb, D.J. (Daniel J.), Haba-Rubio, J. (José), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heinzer, R. (Raphaël), Hixson, J.E. (James E.), Homuth, G. (Georg), Ikram, M.A. (Arfan), Komulainen, P. (Pirjo), Krieger, J.E. (José), Lee, J. (Jiwon), Liu, J. (Jingmin), Lohman, K.K. (Kurt K.), Luik, A.I. (Annemarie), Mägi, R. (Reedik), Martin, L.W. (Lisa), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Nalls, M.A. (Michael), O´Connell, J.R., Peters, A. (Annette), Peyser, P.A. (Patricia A.), Raitakari, O. (Olli), Reiner, A. (Alexander), Rensen, P.C.N. (Patrick), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Roenneberg, T., Rotter, J.I. (Jerome I.), Schreiner, P.J. (Pamela), Shikany, J. (James), Sidney, S.S. (Stephen S.), Sims, M. (Mario), Sitlani, C.M. (Colleen M.), Sofer, T. (Tamar), Strauch, K. (Konstantin), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Völzke, H. (Henry), Waldenberger, M. (Melanie), Wallance, R.B. (Robert B.), van Dijk, K.W. (Ko Willems), Yu, C. (Caizheng), Zonderman, A.B. (Alan B.), Becker, D.M. (Diane), Elliott, P. (Paul), Esko, T. (Tõnu), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), North, K.E. (Kari), Penninx, B.W.J.H. (Brenda), Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wu, T. (Tangchun), Xiang, Y.-B. (Yong-Bing), Zheng, W. (Wei), Arnett, D.K. (Donna), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Kardia, S.L.R. (Sharon), Kelly, T.N. (Tanika N.), Kritchevsky, S.B. (Stephen), Loos, R.J.F. (Ruth), Pereira, A. (A.), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rotimi, C. (Charles), Zhu, X. (Xiaofeng), Amin, N. (Najaf), Cupples, L.A. (L Adrienne), Fornage, M. (Myriam), Fox, E.F. (Ervin F.), Guo, X. (Xiuqing), Gauderman, W.J. (W James), Rice, K.M. (Kenneth), Kooperberg, C. (Charles), Munroe, P. (Patricia), Liu, C.-T. (Ching-Ti), Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Heemst, D. (Diana) van, and Redline, S. (Susan)

Abstract

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

Published
2019
Full Text
View/download PDF

17. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author

Vries, P.S. (Paul) de, Brown, M.R., Bentley, A.R. (Amy), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Schwander, K., Kraja, A. (Aldi), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Huffman, J.E. (Jennifer E.), Musani, S.K. (Solomon K.), Li, C. (Changwei), Feitosa, M.F. (Mary Furlan), Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Deng, X. (Xuan), Dorajoo, R. (Rajkumar), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Evangelou, E. (Evangelos), Graff, M.J. (Maud J.L.), Alver, M. (Maris), Boissel, M. (Mathilde), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gandin, I. (Ilaria), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), Hartwig, F.P. (Fernando P.), He, M. (Meian), Horimoto, A.R.V.R. (Andrea R V R), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Lee, J.H. (Joseph H.), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Matoba, N. (Nana), Nolte, I.M. (Ilja), Pietzner, M. (Maik), Riaz, M. (Muhammad), Said, M.A. (M Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Ballantyne, C. (Christie), Boerwinkle, E.A. (Eric), Broeckel, U. (Ulrich), Campbell, A. (Archie), Canouil, M. (Mickaël), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J. (John), Faire, U. (Ulf) de, de Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, de Silva, H.J. (H Janaka), Ding, J. (Jingzhong), Dominiczak, A.F. (Anna F.), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Eppinga, R.N. (Ruben N.), Faul, J.D. (Jessica D.), Fisher, V. (Virginia), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Ghanbari, M. (Mohsen), Giulianini, F. (Franco), Grabe, H.J. (Hans Jörgen), Grove, M.L. (Megan), Gu, C. (Charles), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Hixson, J.E. (James E.), Howard, B.V. (Barbara V.), Ikram, M.A. (Arfan), Jacobs, D.R. (David R.), Johnson, C. (Craig), Jonas, J.B., Kammerer, C.M. (Candace), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas O.), Koh, W.-P. (Woon-Puay), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kooperberg, C. (Charles), Krieger, J.E. (José), Kritchevsky, S.B. (Steve B.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lemaitre, R.N. (Rozenn ), Li, Y. (Yize), Liang, J. (Jingjing), Liu, J. (Jianjun), Liu, K. (Kiang), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W.), McKenzie, C.A. (Colin A.), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen L.), Mosley, T.H. (Thomas H.), Mukamal, K. (Kenneth), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), O´Connell, J.R., Palmer, N.D. (Nicholette), Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Reiner, A.P. (Alex P.), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Robino, A. (Antonietta), Robinson, J.G. (Jennifer), Rose, L.M. (Lynda M.), Rudan, I. (Igor), Schmidt, C.O. (Carsten O.), Schreiner, P.J. (Pamela), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Tan, N. (Nicholas), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Uitterlinden, A.G. (André), Heemst, D. (Diana) van, Vuckovic, D. (Dragana), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y. (Yujie), Wang, Z. (Zhe), Wei, W.B. (Wen Bin), Williams, C. (Christine), Wilson, G. (Gregory), Wojczynski, M.K. (Mary ), Yao, J. (Jie), Yu, B. (Bing), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Horta, B.L. (Bernardo L.), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Laakso, M. (Markku), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Penninx, B.W.J.H. (Brenda), Pereira, A.C. (Alexandre C.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Wagenknecht, L.E. (Lynne), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda R.), Zheng, W. (Wei), Elliott, P. (Paul), North, K.E. (Kari), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Liu, C.-T. (Ching-Ti), Liu, Y. (YongMei), Psaty, B.M. (Bruce M.), Jarvelin, M.-R. (Marjo-Riitta), Dam, R.M. (Rob) van, Kardia, S.L.R. (Sharon), Dominiczak, A. (Anna), Rotimi, C. (Charles), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin R.), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (Shyong), Wong, T.Y. (Tien Yin), Liu, J. (Jingmin), Rotter, J.I. (Jerome I.), Gauderman, W.J. (W James), Province, M.A. (Michael A.), Munroe, P. (Patricia), Rice, K. (Kenneth), Chasman, D.I. (Daniel), Cupples, L.A. (L Adrienne), Tobin, M.D. (Martin), Morrison, A.C. (Alanna), Vries, P.S. (Paul) de, Brown, M.R., Bentley, A.R. (Amy), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Schwander, K., Kraja, A. (Aldi), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Huffman, J.E. (Jennifer E.), Musani, S.K. (Solomon K.), Li, C. (Changwei), Feitosa, M.F. (Mary Furlan), Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Deng, X. (Xuan), Dorajoo, R. (Rajkumar), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Evangelou, E. (Evangelos), Graff, M.J. (Maud J.L.), Alver, M. (Maris), Boissel, M. (Mathilde), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gandin, I. (Ilaria), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), Hartwig, F.P. (Fernando P.), He, M. (Meian), Horimoto, A.R.V.R. (Andrea R V R), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Lee, J.H. (Joseph H.), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Matoba, N. (Nana), Nolte, I.M. (Ilja), Pietzner, M. (Maik), Riaz, M. (Muhammad), Said, M.A. (M Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Ballantyne, C. (Christie), Boerwinkle, E.A. (Eric), Broeckel, U. (Ulrich), Campbell, A. (Archie), Canouil, M. (Mickaël), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J. (John), Faire, U. (Ulf) de, de Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, de Silva, H.J. (H Janaka), Ding, J. (Jingzhong), Dominiczak, A.F. (Anna F.), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Eppinga, R.N. (Ruben N.), Faul, J.D. (Jessica D.), Fisher, V. (Virginia), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Ghanbari, M. (Mohsen), Giulianini, F. (Franco), Grabe, H.J. (Hans Jörgen), Grove, M.L. (Megan), Gu, C. (Charles), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Hixson, J.E. (James E.), Howard, B.V. (Barbara V.), Ikram, M.A. (Arfan), Jacobs, D.R. (David R.), Johnson, C. (Craig), Jonas, J.B., Kammerer, C.M. (Candace), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas O.), Koh, W.-P. (Woon-Puay), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kooperberg, C. (Charles), Krieger, J.E. (José), Kritchevsky, S.B. (Steve B.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lemaitre, R.N. (Rozenn ), Li, Y. (Yize), Liang, J. (Jingjing), Liu, J. (Jianjun), Liu, K. (Kiang), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W.), McKenzie, C.A. (Colin A.), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen L.), Mosley, T.H. (Thomas H.), Mukamal, K. (Kenneth), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), O´Connell, J.R., Palmer, N.D. (Nicholette), Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Reiner, A.P. (Alex P.), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Robino, A. (Antonietta), Robinson, J.G. (Jennifer), Rose, L.M. (Lynda M.), Rudan, I. (Igor), Schmidt, C.O. (Carsten O.), Schreiner, P.J. (Pamela), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Tan, N. (Nicholas), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Uitterlinden, A.G. (André), Heemst, D. (Diana) van, Vuckovic, D. (Dragana), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y. (Yujie), Wang, Z. (Zhe), Wei, W.B. (Wen Bin), Williams, C. (Christine), Wilson, G. (Gregory), Wojczynski, M.K. (Mary ), Yao, J. (Jie), Yu, B. (Bing), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Horta, B.L. (Bernardo L.), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Laakso, M. (Markku), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Penninx, B.W.J.H. (Brenda), Pereira, A.C. (Alexandre C.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Wagenknecht, L.E. (Lynne), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda R.), Zheng, W. (Wei), Elliott, P. (Paul), North, K.E. (Kari), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Liu, C.-T. (Ching-Ti), Liu, Y. (YongMei), Psaty, B.M. (Bruce M.), Jarvelin, M.-R. (Marjo-Riitta), Dam, R.M. (Rob) van, Kardia, S.L.R. (Sharon), Dominiczak, A. (Anna), Rotimi, C. (Charles), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin R.), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (Shyong), Wong, T.Y. (Tien Yin), Liu, J. (Jingmin), Rotter, J.I. (Jerome I.), Gauderman, W.J. (W James), Province, M.A. (Michael A.), Munroe, P. (Patricia), Rice, K. (Kenneth), Chasman, D.I. (Daniel), Cupples, L.A. (L Adrienne), Tobin, M.D. (Martin), and Morrison, A.C. (Alanna)

Abstract

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Published
2019
Full Text
View/download PDF

18. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author

Kilpeläinen, T.O. (Tuomas), Bentley, A.R. (Amy), Noordam, R., Sung, YJ, Schwander, K., Winkler, T.W. (Thomas), Jakupovic, H., Chasman, D.I. (Daniel), Manning, A., Ntalla, I. (Ioanna), Aschard, H. (Hugues), Brown, M.R., de Las Fuentes, L., Franceschini, N. (Nora), Guo, X. (Xiuqing), Vojinovic, D., Aslibekyan, S, Feitosa, M.F. (Mary Furlan), Kho, M., Musani, SK, Richard, M., Wang, H.M., Wang, Z. (Zhen), Bartz, TM, Bielak, L.F. (Lawrence F.), Campbell, A. (Archie), Dorajoo, R. (Rajkumar), Fisher, V., Hartwig, F.P., Horimoto, A., Li, C.W., Lohman, K. (Kurt), Marten, J, Sim, XL, Smith, A.V. (Davey), Tajuddin, S. M., Alver, M, Amini, M., Boissel, M., Chai, J.F., Chen, X. (Xishu), Divers, J, Evangelou, E. (Evangelos), Gao, C. (Cheng), Graff, M.J. (Maud J.L.), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Zhao, J.H. (Jing Hua), Kraja, A. (Aldi), Kuhnel, B. (Brigitte), Laguzzi, F., Lyytikäinen, L.-P. (Leo-Pekka), Nolte, IM, Rauramaa, R. (Rainer), Riaz, M. (Muhammad), Robino, A. (Antonietta), Rueedi, R, Stringham, H.M. (Heather), Takeuchi, F, Most, P.J. (Peter) van der, Varga, T.V. (Tibor), Verweij, N. (Niek), Ware, EB, Wen, WQ, Li, X. Y., Yanek, L.R. (Lisa), Amin, N. (Najaf), Arnett, D.K. (Donna), Boerwinkle, E.A. (Eric), Brumat, M., Cade, B, Canouil, M., Chen, Y.D.I. (Yii-Der Ida), Concas, MP, Connell, J. (John), Mutsert, R. (Reneé) de, de Silva, H.J., de Vries, PS, Demirkan, A. (Ayşe), Ding, J. (Jingzhong), Eaton, CB, Faul, J.D. (Jessica), Friedlander, Y. (Yechiel), Gabriel, K.P., Ghanbari, M., Giulianini, F. (Franco), Gu, C.C., Gu, DF, Harris, T.B. (Tamara), He, J. (Jing), Heikkinen, S., Heng, C.K. (Chew-Kiat), Hunt, S.C. (Steven), Ikram, M.A. (Arfan), Jonas, J.B., Koh, WP, Komulainen, P. (Pirjo), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, LJ, Leander, K. (Karin), Lemaitre, R.N. (Rozenn ), Lewis, CE, Liang, J.J., Alizadeh, BZ, Boezen, H.M. (Marike), Franke, L. (Lude), Navis, G. (Gerjan), Rots, M., Swertz, M. (Morris), Wolffenbuttel, B.H.R. (Bruce), Wijmenga, C. (Cisca), Liu, J. (Jianjun), Maagi, R., Manichaikul, A. (Ani), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Mohlke, K.L. (Karen), Mosley, T.H. (Thomas), Murray, A.D., Nalls, M.A. (Michael), Nang, EEK, Nelson, C.P. (Christopher), Nona, S., Norris, JM, Nwuba, C.V., O´Connell, J.R., Palmer, N.D. (Nicholette), Papanicolau, GJ, Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Porteous, D.J. (David J.), Poveda, A. (Andrés), Raitakari, OT, Rich, S.S. (Stephen), Risch, N., Robinson, JG, Rose, L.M. (Lynda), Rudan, I. (Igor), Schreiner, PJ, Scott, L.J. (Laura), Sidney, SS, Sims, M, Smith, J.A. (Jennifer A), Snieder, H. (Harold), Sofer, T., Starr, J.M. (John), Sternfeld, B., Strauch, K. (Konstantin), Tang, H. (Hui), Taylor, K.D. (Kent), Tsai, M.Y. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), van der Ende, M.Y., Heemst, D. van, Voortman, R.G. (Trudy), Waldenberger, M. (Melanie), Wennberg, P. (Patrik), Wilson, G, Xiang, YB, Yao, J, Yu, C.Z., Yuan, JM, Zhao, W. (Wei), Zonderman, A.B. (Alan), Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, DW, Faire, U. (Ulf) de, Deary, I.J. (Ian), Elliott, P.M. (Perry), Esko, T. (Tõnu), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Kato, N, Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimaki, T, Magnusson, P.K. (Patrik), Oldenhinkel, A.J. (A.), Penninx, B.W.J.H. (Brenda), Samani, N.J. (Nilesh), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wang, Y. (Ying), Wareham, N.J. (Nick), Weir, D.R. (David), Wu, TC, Zheng, W. (Wei), Zhu, X. (Xiaofeng), Evans, MK, Franks, P.W. (Paul), Guonason, V. (Vilmundur), Hayward, C. (Caroline), Horta, BL, Kelly, TN, Liu, Y. (YongMei), North, K.E. (Kari), Pereira, AC, Ridker, P.M. (Paul), Tai, E.S. (Shyong), Dam, R.M. (Rob) van, Fox, E.R. (Ervin), Kardia, S.L.R. (Sharon), Liu, C.-T. (Ching-Ti), Mook-Kanamori, D.O. (Dennis), Province, M.A. (Mike), Redline, S. (Susan), Duijn, C.M., Rotter, J.I. (Jerome), Kooperberg, C.B., Gauderman, W.J. (W James), Psaty, B.M. (Bruce), Rice, K, Munroe, P. (Patricia), Fornage, M. (Myriam), Cupples, L.A. (Adrienne), Rotimi, CN, Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Bentley, A.R. (Amy), Noordam, R., Sung, YJ, Schwander, K., Winkler, T.W. (Thomas), Jakupovic, H., Chasman, D.I. (Daniel), Manning, A., Ntalla, I. (Ioanna), Aschard, H. (Hugues), Brown, M.R., de Las Fuentes, L., Franceschini, N. (Nora), Guo, X. (Xiuqing), Vojinovic, D., Aslibekyan, S, Feitosa, M.F. (Mary Furlan), Kho, M., Musani, SK, Richard, M., Wang, H.M., Wang, Z. (Zhen), Bartz, TM, Bielak, L.F. (Lawrence F.), Campbell, A. (Archie), Dorajoo, R. (Rajkumar), Fisher, V., Hartwig, F.P., Horimoto, A., Li, C.W., Lohman, K. (Kurt), Marten, J, Sim, XL, Smith, A.V. (Davey), Tajuddin, S. M., Alver, M, Amini, M., Boissel, M., Chai, J.F., Chen, X. (Xishu), Divers, J, Evangelou, E. (Evangelos), Gao, C. (Cheng), Graff, M.J. (Maud J.L.), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Zhao, J.H. (Jing Hua), Kraja, A. (Aldi), Kuhnel, B. (Brigitte), Laguzzi, F., Lyytikäinen, L.-P. (Leo-Pekka), Nolte, IM, Rauramaa, R. (Rainer), Riaz, M. (Muhammad), Robino, A. (Antonietta), Rueedi, R, Stringham, H.M. (Heather), Takeuchi, F, Most, P.J. (Peter) van der, Varga, T.V. (Tibor), Verweij, N. (Niek), Ware, EB, Wen, WQ, Li, X. Y., Yanek, L.R. (Lisa), Amin, N. (Najaf), Arnett, D.K. (Donna), Boerwinkle, E.A. (Eric), Brumat, M., Cade, B, Canouil, M., Chen, Y.D.I. (Yii-Der Ida), Concas, MP, Connell, J. (John), Mutsert, R. (Reneé) de, de Silva, H.J., de Vries, PS, Demirkan, A. (Ayşe), Ding, J. (Jingzhong), Eaton, CB, Faul, J.D. (Jessica), Friedlander, Y. (Yechiel), Gabriel, K.P., Ghanbari, M., Giulianini, F. (Franco), Gu, C.C., Gu, DF, Harris, T.B. (Tamara), He, J. (Jing), Heikkinen, S., Heng, C.K. (Chew-Kiat), Hunt, S.C. (Steven), Ikram, M.A. (Arfan), Jonas, J.B., Koh, WP, Komulainen, P. (Pirjo), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, LJ, Leander, K. (Karin), Lemaitre, R.N. (Rozenn ), Lewis, CE, Liang, J.J., Alizadeh, BZ, Boezen, H.M. (Marike), Franke, L. (Lude), Navis, G. (Gerjan), Rots, M., Swertz, M. (Morris), Wolffenbuttel, B.H.R. (Bruce), Wijmenga, C. (Cisca), Liu, J. (Jianjun), Maagi, R., Manichaikul, A. (Ani), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Mohlke, K.L. (Karen), Mosley, T.H. (Thomas), Murray, A.D., Nalls, M.A. (Michael), Nang, EEK, Nelson, C.P. (Christopher), Nona, S., Norris, JM, Nwuba, C.V., O´Connell, J.R., Palmer, N.D. (Nicholette), Papanicolau, GJ, Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Porteous, D.J. (David J.), Poveda, A. (Andrés), Raitakari, OT, Rich, S.S. (Stephen), Risch, N., Robinson, JG, Rose, L.M. (Lynda), Rudan, I. (Igor), Schreiner, PJ, Scott, L.J. (Laura), Sidney, SS, Sims, M, Smith, J.A. (Jennifer A), Snieder, H. (Harold), Sofer, T., Starr, J.M. (John), Sternfeld, B., Strauch, K. (Konstantin), Tang, H. (Hui), Taylor, K.D. (Kent), Tsai, M.Y. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), van der Ende, M.Y., Heemst, D. van, Voortman, R.G. (Trudy), Waldenberger, M. (Melanie), Wennberg, P. (Patrik), Wilson, G, Xiang, YB, Yao, J, Yu, C.Z., Yuan, JM, Zhao, W. (Wei), Zonderman, A.B. (Alan), Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, DW, Faire, U. (Ulf) de, Deary, I.J. (Ian), Elliott, P.M. (Perry), Esko, T. (Tõnu), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Kato, N, Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimaki, T, Magnusson, P.K. (Patrik), Oldenhinkel, A.J. (A.), Penninx, B.W.J.H. (Brenda), Samani, N.J. (Nilesh), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wang, Y. (Ying), Wareham, N.J. (Nick), Weir, D.R. (David), Wu, TC, Zheng, W. (Wei), Zhu, X. (Xiaofeng), Evans, MK, Franks, P.W. (Paul), Guonason, V. (Vilmundur), Hayward, C. (Caroline), Horta, BL, Kelly, TN, Liu, Y. (YongMei), North, K.E. (Kari), Pereira, AC, Ridker, P.M. (Paul), Tai, E.S. (Shyong), Dam, R.M. (Rob) van, Fox, E.R. (Ervin), Kardia, S.L.R. (Sharon), Liu, C.-T. (Ching-Ti), Mook-Kanamori, D.O. (Dennis), Province, M.A. (Mike), Redline, S. (Susan), Duijn, C.M., Rotter, J.I. (Jerome), Kooperberg, C.B., Gauderman, W.J. (W James), Psaty, B.M. (Bruce), Rice, K, Munroe, P. (Patricia), Fornage, M. (Myriam), Cupples, L.A. (Adrienne), Rotimi, CN, Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), and Loos, R.J.F. (Ruth)

Abstract

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 l

Published
2019
Full Text
View/download PDF

19. Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Author

Vallejo-Vaz, A.J. Marco, M.D. Stevens, C.A.T. Akram, A. Freiberger, T. Hovingh, G.K. Kastelein, J.J.P. Mata, P. Raal, F.J. Santos, R.D. Soran, H. Watts, G.F. Abifadel, M. Aguilar-Salinas, C.A. Al-Khnifsawi, M. Alkindi, F.A. Alnouri, F. Alonso, R. Al-Rasadi, K. Al-Sarraf, A. Ashavaid, T.F. Binder, C.J. Bogsrud, M.P. Bourbon, M. Bruckert, E. Chlebus, K. Corral, P. Descamps, O. Durst, R. Ezhov, M. Fras, Z. Genest, J. Groselj, U. Harada-Shiba, M. Kayikcioglu, M. Lalic, K. Lam, C.S.P. Latkovskis, G. Laufs, U. Liberopoulos, E. Lin, J. Maher, V. Majano, N. Marais, A.D. März, W. Mirrakhimov, E. Miserez, A.R. Mitchenko, O. Nawawi, H.M. Nordestgaard, B.G. Paragh, G. Petrulioniene, Z. Pojskic, B. Postadzhiyan, A. Reda, A. Reiner, Ž. Sadoh, W.E. Sahebkar, A. Shehab, A. Shek, A.B. Stoll, M. Su, T.-C. Subramaniam, T. Susekov, A.V. Symeonides, P. Tilney, M. Tomlinson, B. Truong, T.-H. Tselepis, A.D. Tybjærg-Hansen, A. Vázquez-Cárdenas, A. Viigimaa, M. Vohnout, B. Widén, E. Yamashita, S. Banach, M. Gaita, D. Jiang, L. Nilsson, L. Santos, L.E. Schunkert, H. Tokgözoğlu, L. Car, J. Catapano, A.L. Ray, K.K. Schreier, L. Pang, J. Dieplinger, H. Hanauer-Mader, G. Desutter, J. Langlois, M. Mertens, A. Rietzschel, E. Wallemacq, C. Isakovic, D. Dzankovic, A.M. Obralija, J. Pojskic, L. Sisic, I. Stimjanin, E. Torlak, V.A. Jannes, C.E. Krieger, J.E. Pereira, A.C. Ruel, I. Asenjo, S. Cuevas, A. Pećin, I. Miltiadous, G. Panayiotou, A.G. Vrablik, M. Benn, M. Heinsar, S. Béliard, S. Gouni-Berthold, I. Hengstenberg, W. Julius, U. Kassner, U. Klose, G. König, C. König, W. Otte, B. Parhofer, K. Schatz, U. Schmidt, N. Steinhagen-Thiessen, E. Vogt, A. Antza, C. Athyros, V. Bilianou, E. Boufidou, A. Chrousos, G. Elisaf, M. Garoufi, A. Katsiki, N. Kolovou, G. Kotsis, V. Rallidis, L. Rizos, C. Skalidis, E. Skoumas, I. Tziomalos, K. Shawney, J.P.S. Abbaszadegan, M.R. Aminzadeh, M. Hosseini, S. Mobini, M. Vakili, R. Zaeri, H. Agar, R. Boran, G. Colwell, N. Crowley, V. Durkin, M. Griffin, D. Kelly, M. Rakovac-Tisdall, A. Bitzur, R. Cohen, H. Eliav, O. Ellis, A. Gavish, D. Harats, D. Henkin, Y. Knobler, H. Leavit, L. Leitersdorf, E. Schurr, D. Shpitzen, S. Szalat, A. Arca, M. Averna, M. Bertolini, S. Calandra, S. Tarugi, P. Erglis, A. Gilis, D. Nesterovics, G. Saripo, V. Upena-Roze, A. Elbitar, S. Jambart, S. Khoury, P.E. Gargalskaite, U. Kutkiene, S. Al-Khateeb, A. An, C.Y. Ismail, Z. Kasim, S. Ibrahim, K.S. Radzi, A.B.M. Kasim, N.A. Nor, N.S.M. Ramli, A.S. Razak, S.A. Muid, S. Rosman, A. Sanusi, A.R. Razman, A.Z. Nazli, S.A. Kek, T.L. Azzopardi, C. Aguilar Salinas, C.A. Galán, G. Rubinstein, A. Magaña-Torres, M.T. Martagon, A. Mehta, R. Wittekoek, M.E. Isara, A.R. Obaseki, D.E. Ohenhen, O.A. Holven, K.B. Gruchała, M. Baranowska, M. Borowiec-Wolny, J. Gilis-Malinowska, N. Michalska-Grzonkowska, A. Pajkowski, M. Parczewska, A. Romanowska-Kocejko, M. Stróżyk, A. Żarczyńska-Buchowiecka, M. Kleinschmidt, M. Alves, A.C. Medeiros, A.M. Ershova, A. Korneva, V. Kuznetsova, T. Malyshev, P. Meshkov, A. Rozhkova, T. Popovic, L. Lukac, S.S. Stosic, L. Rasulic, I. Lalic, N.M. Chua, T.S.J. Ting, S.P.L. Raslova, K. Battelino, T. Cevc, M. Jug, B. Kovac, J. Podkrajsek, K.T. Sustar, U. Trontelj, K.J. Marais, D. Isla, L.P. Martin, F.J. Charng, M.-J. Chen, P.-L. Kayikçioglu, M. Dell’oca, N. Fernández, G. Ressia, A. Reyes, X. Zelarayan, M. Alieva, R.B. Hoshimov, S.U. Nizamov, U.I. Kurbanov, R.D. Lima-Martínez, M.M. Nguyen, M.-N.T. Do, D.-L. Kim, N.-T. Le, T.-T. Le, H.-A.

Abstract

Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed. © 2018 Elsevier B.V.

Published
2018

22. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K i

Author

Feitosa, M.F. (Mary Furlan), Kraja, A. (Aldi), Chasman, D.I. (Daniel), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Marten, J. (Jonathan), Musani, S.K. (Solomon K.), Li, C. (Changwei), Bentley, A.R. (Amy), Brown, M.R., Schwander, K., Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Dorajoo, R. (Rajkumar), Fisher, V. (Virginia), Hartwig, F.P. (Fernando P.), Horimoto, A.R.V.R. (Andrea R. V.R.), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Wojczynski, M.K. (Mary ), Alver, M. (Maris), Boissel, M. (Mathilde), Cai, Q. (Qiuyin), Campbell, A. (Archie), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kähönen, M. (Mika), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Luan, J., Matoba, N. (Nana), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Riaz, M. (Muhammad), Rueedi, R. (Rico), Robino, A. (Antonietta), Said, M.A. (M. Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Vitart, V. (Veronique), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Warren, H. (Helen), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Broeckel, U. (Ulrich), Brown, M. (Morris), Brumat, M. (Marco), Burke, G.L. (Greg), Canouil, M. (Mickaël), Chakravarti, A. (Aravinda), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J.M. (John M.), Correa, D.D., De Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, De Silva, H.J. (H. Janaka), Deng, X. (Xuan), Ding, J. (Jingzhong), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Ehret, G. (Georg), Eppinga, R.N. (Ruben N.), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Felix, S.B. (Stephan B.), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Gandin, I. (Ilaria), Gao, H. (He), Ghanbari, M. (Mohsen), Gigante, B. (Bruna), Gu, C. (Charles), Gu, D. (Dongfeng), Hagenaars, S. (Saskia), Hallmans, G. (Göran), Harris, T.B. (Tamara), He, J. (Jiang), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Howard, B.V. (Barbara V.), Ikram, M.K. (Kamran), John, U. (Ulrich), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas), Koh, W.-P. (Woon-Puay), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lewis, C.E. (Cora E.), Li, Y. (Yize), Lin, S. (Shiow), Liu, J. (Jianjun), Liu, J. (Jingmin), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), McKenzie, C.A. (Colin), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen), Momozawa, Y. (Yukihide), Nalls, M.A. (Michael), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), Norris, J.M. (Jill M.), O´Connell, J.R., Palmer, N.D. (Nicholette), Perls, T.T. (Thomas T.), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Roll, K. (Kathryn), Rose, L.M. (Lynda M.), Rosendaal, F.R. (Frits), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten Oliver), Schreiner, P.J. (Pamela), Schupf, N. (Nicole), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Sitlani, C.M. (Colleen), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Stringham, H.M. (Heather M.), Tan, N.Y.Q. (Nicholas Y.Q.), Tang, H. (Hua), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Turner, S.T. (Stephen T.), Uitterlinden, A.G. (André), Vollenweider, P. (Peter), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y.X. (Ya Xing), Wei, W.B. (Wen Bin), Williams, C. (Christine), Yao, J. (Jie), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Jonas, J.B. (Jost Bruno), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Kutalik, Z. (Zoltán), Laakso, M. (Markku), Laurie, C.C. (Cathy C.), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Oldehinkel, A.J. (Albertine), Penninx, B.W.J.H. (Brenda), Polasek, O. (Ozren), Porteous, D.J. (David J.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh J.), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Van Der Harst, P. (Pim), Wagenknecht, L.E. (Lynne), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda), Wu, T. (Tangchun), Zheng, W. (Wei), Bouchard, C. (Claude), Christensen, K. (Kaare), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Horta, B.L. (Bernardo L.), Kardia, S.L.R. (Sharon L.R.), Liu, Y. (YongMei), Pereira, A.C. (Alexandre C.), Psaty, B.M. (Bruce M.), Ridker, P.M. (Paul), Dam, R.M. (Rob) van, Gauderman, W.J. (W James), Zhu, X. (Xiaofeng), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Rotimi, C. (Charles), Cupples, L.A. (Adrienne), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (E. Shyong), Wong, T.Y. (Tien Yin), Kooperberg, C. (Charles), Palmas, W. (Walter), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Elliott, P. (Paul), Caulfield, M. (Mark), Munroe, P. (Patricia), Rao, D.C. (Dabeeru C.), Province, M.A. (Mike), Levy, D. (Daniel), Feitosa, M.F. (Mary Furlan), Kraja, A. (Aldi), Chasman, D.I. (Daniel), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Marten, J. (Jonathan), Musani, S.K. (Solomon K.), Li, C. (Changwei), Bentley, A.R. (Amy), Brown, M.R., Schwander, K., Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Dorajoo, R. (Rajkumar), Fisher, V. (Virginia), Hartwig, F.P. (Fernando P.), Horimoto, A.R.V.R. (Andrea R. V.R.), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Wojczynski, M.K. (Mary ), Alver, M. (Maris), Boissel, M. (Mathilde), Cai, Q. (Qiuyin), Campbell, A. (Archie), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kähönen, M. (Mika), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Luan, J., Matoba, N. (Nana), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Riaz, M. (Muhammad), Rueedi, R. (Rico), Robino, A. (Antonietta), Said, M.A. (M. Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Vitart, V. (Veronique), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Warren, H. (Helen), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Broeckel, U. (Ulrich), Brown, M. (Morris), Brumat, M. (Marco), Burke, G.L. (Greg), Canouil, M. (Mickaël), Chakravarti, A. (Aravinda), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J.M. (John M.), Correa, D.D., De Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, De Silva, H.J. (H. Janaka), Deng, X. (Xuan), Ding, J. (Jingzhong), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Ehret, G. (Georg), Eppinga, R.N. (Ruben N.), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Felix, S.B. (Stephan B.), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Gandin, I. (Ilaria), Gao, H. (He), Ghanbari, M. (Mohsen), Gigante, B. (Bruna), Gu, C. (Charles), Gu, D. (Dongfeng), Hagenaars, S. (Saskia), Hallmans, G. (Göran), Harris, T.B. (Tamara), He, J. (Jiang), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Howard, B.V. (Barbara V.), Ikram, M.K. (Kamran), John, U. (Ulrich), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas), Koh, W.-P. (Woon-Puay), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lewis, C.E. (Cora E.), Li, Y. (Yize), Lin, S. (Shiow), Liu, J. (Jianjun), Liu, J. (Jingmin), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), McKenzie, C.A. (Colin), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen), Momozawa, Y. (Yukihide), Nalls, M.A. (Michael), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), Norris, J.M. (Jill M.), O´Connell, J.R., Palmer, N.D. (Nicholette), Perls, T.T. (Thomas T.), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Roll, K. (Kathryn), Rose, L.M. (Lynda M.), Rosendaal, F.R. (Frits), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten Oliver), Schreiner, P.J. (Pamela), Schupf, N. (Nicole), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Sitlani, C.M. (Colleen), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Stringham, H.M. (Heather M.), Tan, N.Y.Q. (Nicholas Y.Q.), Tang, H. (Hua), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Turner, S.T. (Stephen T.), Uitterlinden, A.G. (André), Vollenweider, P. (Peter), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y.X. (Ya Xing), Wei, W.B. (Wen Bin), Williams, C. (Christine), Yao, J. (Jie), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Jonas, J.B. (Jost Bruno), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Kutalik, Z. (Zoltán), Laakso, M. (Markku), Laurie, C.C. (Cathy C.), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Oldehinkel, A.J. (Albertine), Penninx, B.W.J.H. (Brenda), Polasek, O. (Ozren), Porteous, D.J. (David J.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh J.), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Van Der Harst, P. (Pim), Wagenknecht, L.E. (Lynne), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda), Wu, T. (Tangchun), Zheng, W. (Wei), Bouchard, C. (Claude), Christensen, K. (Kaare), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Horta, B.L. (Bernardo L.), Kardia, S.L.R. (Sharon L.R.), Liu, Y. (YongMei), Pereira, A.C. (Alexandre C.), Psaty, B.M. (Bruce M.), Ridker, P.M. (Paul), Dam, R.M. (Rob) van, Gauderman, W.J. (W James), Zhu, X. (Xiaofeng), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Rotimi, C. (Charles), Cupples, L.A. (Adrienne), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (E. Shyong), Wong, T.Y. (Tien Yin), Kooperberg, C. (Charles), Palmas, W. (Walter), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Elliott, P. (Paul), Caulfield, M. (Mark), Munroe, P. (Patricia), Rao, D.C. (Dabeeru C.), Province, M.A. (Mike), and Levy, D. (Daniel)

Abstract

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3, 514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 × 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2, 159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Published
2018
Full Text
View/download PDF

26. Ethnic-Specific Normative Reference Values for Echocardiographic LA and LV Size, LV Mass, and Systolic Function

Author

Poppe, K.K., primary, Doughty, R.N., additional, Gardin, J.M., additional, Hobbs, F.D.R., additional, McMurray, J.J.V., additional, Nagueh, S.F., additional, Senior, R., additional, Thomas, L., additional, Whalley, G.A., additional, Aune, E., additional, Brown, A., additional, Badano, L.P., additional, Cameron, V., additional, Chadha, D.S., additional, Chahal, N., additional, Chien, K.L., additional, Daimon, M., additional, Dalen, H., additional, Detrano, R., additional, Akif Duzenli, M., additional, Ezekowitz, J., additional, de Simone, G., additional, Di Pasquale, P., additional, Fukuda, S., additional, Gill, P.S., additional, Grossman, E., additional, Kim, H.-K., additional, Kuznetsova, T., additional, Leung, N.K.W., additional, Linhart, A., additional, McDonagh, T.A., additional, McGrady, M., additional, Mill, J.G., additional, Mogelvang, R., additional, Muiesan, M.L., additional, Ng, A.C.T., additional, Ojji, D., additional, Otterstad, J.E., additional, Petrovic, D.J., additional, Poppe, K.K., additional, Prendergast, B., additional, Rietzschel, E., additional, Schirmer, H., additional, Schvartzman, P., additional, Simova, I., additional, Sliwa, K., additional, Stewart, S., additional, Squire, I.B., additional, Takeuchi, M., additional, Altman, D.G., additional, Perera, R., additional, Triggs, C.M., additional, Au Yeung, H., additional, Beans Picón, G.A., additional, Anderson, T., additional, Dyck, J., additional, Ezekowitz, J.A., additional, Chirinos, J.A., additional, De Buyzere, M.L., additional, Gillebert, T.C., additional, Segers, P., additional, Van daele, C.M., additional, Walsh, H.A., additional, Izzo, R., additional, De Luca, N., additional, Trimarco, B., additional, Goel, K., additional, Misra, A., additional, Chen, P.-C., additional, Lin, H.-J., additional, Su, T.-C., additional, Richards, A.M., additional, Troughton, R., additional, Skov Jensen, J., additional, Paterna, S., additional, Davies, M.K., additional, Davis, R.C., additional, Roalfe, A., additional, Calvert, M., additional, Freemantle, N., additional, Lip, G.Y.H., additional, Staessen, J.A., additional, Dargie, H.J., additional, Ford, I., additional, Galasko, G., additional, Lahiri, A., additional, Carrington, M., additional, Krum, H., additional, Zeitz, C., additional, Blauwet, L., additional, Moelmen Hansen, H.E., additional, Støylen, A., additional, Thorstensen, A., additional, Watanabe, H., additional, Yoshikawa, J., additional, Chambers, J.C., additional, Kooner, J., additional, Davies, J., additional, Loke, I., additional, Ng, L., additional, Leung, D.Y., additional, Arnold, L., additional, Coffey, S., additional, d'Arcy, J., additional, Hammond, C., additional, Mabbett, C., additional, Lima, C., additional, Loudon, M., additional, Pinheiro, N., additional, Reynolds, R., additional, Muraru, D., additional, Peluso, D., additional, Dal Bianco, L., additional, Petrovic, J., additional, Fuchs, F.D., additional, Katova, T., additional, Kaku, K., additional, Boyd, A., additional, Chia, E.M., additional, Angelo, L.C., additional, Pereira, A.C., additional, Krieger, J.E., additional, Rodrigues, S.L., additional, Paini, A., additional, Agabiti Rosei, E., additional, and Salvetti, M., additional

Published
2015
Full Text
View/download PDF

27. The Agamma-195 (C->G) mutation in hereditary persistence of fetal hemoglobin is not associated with activation of a reporter gene in vitro

Author

Schreiber, R., Gonçalves, M.S., Junqueira, M.L., Saad, S.T.O., Krieger, J.E., and Costa, F.F.

Subjects
HPFH, fetal hemoglobin, hereditary persistence of fetal hemoglobin, transient expression
Abstract

Hereditary persistence of fetal hemoglobin is an uncommon, benign disorder in which the expression of gamma-globin genes persists into adult life. Several point mutations have been associated with the increased gamma-globin gene promoter activity. We evaluated the -195 (C->G) mutation by a functional in vitro assay based on the luciferase reporter gene system. The results indicated that the increased promoter activity observed in vivo could not be reproduced in vitro under the conditions employed, suggesting that other factors may be involved in the overexpression of the gamma-globin gene containing the -195 (C->G) mutation. Furthermore, this is the first time that the -195 (C->G) mutation of the Agamma-globin gene has been evaluated by in vitro gene expression.

Published
2001

Catalog

Books, media, physical & digital resources
See catalog results