Search

Your search keyword '"Nordestgaard, Børge G"' showing total 2 results
Start Over "Nordestgaard, Børge G" Topic coronary disease Publisher escholarship, university of california
2 results on '"Nordestgaard, Børge G"'

1. Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

Author

Zhao, Wei, Rasheed, Asif, Tikkanen, Emmi, Lee, Jung-Jin, Butterworth, Adam S, Howson, Joanna MM, Assimes, Themistocles L, Chowdhury, Rajiv, Orho-Melander, Marju, Damrauer, Scott, Small, Aeron, Asma, Senay, Imamura, Minako, Yamauch, Toshimasa, Chambers, John C, Chen, Peng, Sapkota, Bishwa R, Shah, Nabi, Jabeen, Sehrish, Surendran, Praveen, Lu, Yingchang, Zhang, Weihua, Imran, Atif, Abbas, Shahid, Majeed, Faisal, Trindade, Kevin, Qamar, Nadeem, Mallick, Nadeem Hayyat, Yaqoob, Zia, Saghir, Tahir, Rizvi, Syed Nadeem Hasan, Memon, Anis, Rasheed, Syed Zahed, Memon, Fazal-ur-Rehman, Mehmood, Khalid, Ahmed, Naveeduddin, Qureshi, Irshad Hussain, Tanveer-us-Salam, Iqbal, Wasim, Malik, Uzma, Mehra, Narinder, Kuo, Jane Z, Sheu, Wayne H-H, Guo, Xiuqing, Hsiung, Chao A, Juang, Jyh-Ming J, Taylor, Kent D, Hung, Yi-Jen, Lee, Wen-Jane, Quertermous, Thomas, Lee, I-Te, Hsu, Chih-Cheng, Bottinger, Erwin P, Ralhan, Sarju, Teo, Yik Ying, Wang, Tzung-Dau, Alam, Dewan S, Di Angelantonio, Emanuele, Epstein, Steve, Nielsen, Sune F, Nordestgaard, Børge G, Tybjaerg-Hansen, Anne, Young, Robin, Benn, Marianne, Frikke-Schmidt, Ruth, Kamstrup, Pia R, Jukema, J Wouter, Sattar, Naveed, Smit, Roelof, Chung, Ren-Hua, Liang, Kae-Woei, Anand, Sonia, Sanghera, Dharambir K, Ripatti, Samuli, Loos, Ruth JF, Kooner, Jaspal S, Tai, E Shyong, Rotter, Jerome I, Chen, Yii-Der Ida, Frossard, Philippe, Maeda, Shiro, Kadowaki, Takashi, Reilly, Muredach, Pare, Guillaume, Melander, Olle, Salomaa, Veikko, Rader, Daniel J, Danesh, John, Voight, Benjamin F, and Saleheen, Danish

Subjects
Biological Sciences, Genetics, Obesity, Human Genome, Heart Disease - Coronary Heart Disease, Clinical Research, Heart Disease, Diabetes, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Asia, Asian People, Biomarkers, Comorbidity, Coronary Disease, Diabetes Mellitus, Type 2, Europe, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-DRB5 Chains, Humans, Metabolic Networks and Pathways, Metabolic Syndrome, Molecular Targeted Therapy, Mutation, Missense, Polymorphism, Single Nucleotide, Risk Factors, White People, CHD Exome+ Consortium, EPIC-CVD Consortium, EPIC-Interact Consortium, Michigan Biobank, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.

Published
2017

2. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

Author

Scott, Robert A, Freitag, Daniel F, Li, Li, Chu, Audrey Y, Surendran, Praveen, Young, Robin, Grarup, Niels, Stancáková, Alena, Chen, Yuning, Varga, Tibor V, Yaghootkar, Hanieh, Luan, Jian’an, Zhao, Jing Hua, Willems, Sara M, Wessel, Jennifer, Wang, Shuai, Maruthur, Nisa, Michailidou, Kyriaki, Pirie, Ailith, van der Lee, Sven J, Gillson, Christopher, Al Olama, Ali Amin, Amouyel, Philippe, Arriola, Larraitz, Arveiler, Dominique, Aviles-Olmos, Iciar, Balkau, Beverley, Barricarte, Aurelio, Barroso, Inês, Garcia, Sara Benlloch, Bis, Joshua C, Blankenberg, Stefan, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Borecki, Ingrid B, Bork-Jensen, Jette, Bowden, Sarah, Caldas, Carlos, Caslake, Muriel, consortium, The CVD50, Cupples, L Adrienne, Cruchaga, Carlos, Czajkowski, Jacek, Hoed, Marcel den, Dunn, Janet A, Earl, Helena M, Ehret, Georg B, Ferrannini, Ele, Ferrieres, Jean, Foltynie, Thomas, Ford, Ian, Forouhi, Nita G, Gianfagna, Francesco, Gonzalez, Carlos, Grioni, Sara, Hiller, Louise, Jansson, Jan-Håkan, Jørgensen, Marit E, Jukema, J Wouter, Kaaks, Rudolf, Kee, Frank, Kerrison, Nicola D, Key, Timothy J, Kontto, Jukka, Kote-Jarai, Zsofia, Kraja, Aldi T, Kuulasmaa, Kari, Kuusisto, Johanna, Linneberg, Allan, Liu, Chunyu, Marenne, Gaëlle, Mohlke, Karen L, Morris, Andrew P, Muir, Kenneth, Müller-Nurasyid, Martina, Munroe, Patricia B, Navarro, Carmen, Nielsen, Sune F, Nilsson, Peter M, Nordestgaard, Børge G, Packard, Chris J, Palli, Domenico, Panico, Salvatore, Peloso, Gina M, Perola, Markus, Peters, Annette, Poole, Christopher J, Quirós, J Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Salomaa, Veikko, Sánchez, María-José, Sattar, Naveed, Sharp, Stephen J, Sims, Rebecca, Slimani, Nadia, Smith, Jennifer A, Thompson, Deborah J, and Trompet, Stella

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Diabetes, Human Genome, Cardiovascular, Prevention, Obesity, Genetics, Heart Disease, Heart Disease - Coronary Heart Disease, Clinical Trials and Supportive Activities, Aetiology, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Alleles, Coronary Disease, Diabetes Mellitus, Type 2, Dipeptidyl Peptidase 4, Genotype, Glucagon-Like Peptide-1 Receptor, Humans, Receptor, Cannabinoid, CB2, Receptor, Serotonin, 5-HT2C, Receptors, Somatostatin, Sodium-Glucose Transporter 1, CVD50 consortium, GERAD_EC Consortium, Neurology Working Group of the Cohorts for Heart, Aging Research in Genomic Epidemiology, Alzheimer’s Disease Genetics Consortium, Pancreatic Cancer Cohort Consortium, European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease, EPIC-InterAct, CHARGE consortium, CHD Exome+ Consortium, CARDIOGRAM Exome Consortium, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results