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369 results on '"McDonough, Caitrin W."'

2. Effectiveness of Clopidogrel vs Alternative P2Y12 Inhibitors Based on the ABCD-GENE Score

Author

Thomas, Cameron D., Franchi, Francesco, Rossi, Joseph S., Keeley, Ellen C., Anderson, R. David, Beitelshees, Amber L., Duarte, Julio D., Ortega-Paz, Luis, Gong, Yan, Kerensky, Richard A., Kulick, Natasha, McDonough, Caitrin W., Nguyen, Anh B., Wang, Yehua, Winget, Marshall, Yang, William E., Johnson, Julie A., Winterstein, Almut G., Stouffer, George A., Angiolillo, Dominick J., Lee, Craig R., and Cavallari, Larisa H.

Published
2024
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3. Assessing the Performance of In silico Tools and Molecular Dynamics Simulations for Predicting Pharmacogenetic Variant Impact.

Author

AlSaeed, Maryam Jamal, Ramdhan, Peter, Malave, Jean Gabriel, Eljilany, Islam, Langaee, Taimour, McDonough, Caitrin W., Seabra, Gustavo, Li, Chenglong, and Cavallari, Larisa H.

Subjects
SINGLE nucleotide polymorphisms, MOLECULAR dynamics, CYTOCHROME P-450 CYP2D6, CYTOCHROME P-450 CYP2C19, ALLELES
Abstract

The ability of freely available in silico tools to predict the effect of non‐synonymous single nucleotide polymorphisms (nsSNPs) in pharmacogenes on protein function is not well defined. We assessed the performance of seven sequence‐based (SIFT, PolyPhen2, mutation accessor, FATHMM, PhD‐SNP, MutPred2, and SNPs & Go) and five structure‐based (mCSM, SDM, DDGun, CupSat, and MAESTROweb) tools in predicting the impact of 118 nsSNPs in the CYP2C19, CYP2C9, CYP2B6, CYP2D6, and DPYD genes with known function (24 normal, one increased, 42 decreased, and 51 no‐function). Sequence‐based tools had a higher median (IQR) positive predictive value (89% [89–94%] vs. 12% [10–15%], P < 0.001) and lower negative predictive value (30% [24–34%] vs. 90% [80–93%], P < 0.001) than structure‐based tools. Accuracy did not significantly differ between sequence‐based (59% [37–67%]) and structure‐based (34% [23–44%]) tools (P = 0.070). Notably, the no‐function CYP2C9*3 allele and decreased function CYP2C9*8 allele were predicted incorrectly as tolerated by 100% of sequenced‐based tools and as stabilizing by 60% and 20% of structure‐based tools, respectively. As a case study, we performed mutational analysis for the CYP2C9*1, *3 (I359L), and *8 (R150H) proteins through molecular dynamic (MD) simulations using S‐warfarin as the substrate. The I359L variant increased the distance of the major metabolic site of S‐warfarin to the oxy‐ferryl center of CYP2C9, and I359L and R150H caused shifts in the conformation of S‐warfarin to a position less favorable for metabolism. These data suggest that MD simulations may better capture the impact of nsSNPs in pharmacogenes than other tools. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Use of CYP2D6 Inhibitors with CYP2D6 Opioids: Association with Emergency Department Visits for Pain.

Author

Nahid, Noor Ahmed, McDonough, Caitrin W., Wei, Yu‐Jung Jenny, Cicali, Emily J., Gong, Yan, Fillingim, Roger B., and Johnson, Julie A.

Subjects
EMERGENCY room visits, CYTOCHROME P-450, ELECTRONIC health records, CYTOCHROME P-450 CYP2D6, HOSPITAL emergency services, ANTIDEPRESSANTS
Abstract

Hydrocodone, tramadol, codeine, and oxycodone are commonly prescribed opioids that rely on activation by cytochrome P450 2D6 (CYP2D6). CYP2D6 inhibitors can significantly decrease CYP2D6 activity, leading to reduced generation of active metabolites, and impairing pain control. To understand this impact, we assessed emergency department (ED) visits in patients initiating these CYP2D6‐dependent opioids while on CYP2D6‐inhibitor antidepressants vs. antidepressants that do not inhibit CYP2D6. This retrospective cohort study included adult patients prescribed CYP2D6‐dependent opioids utilizing electronic health records data from the University of Florida Health (2015–2021). The association between ED visits and inhibitor exposure was tested using multivariable logistic regression. The primary analysis had 12,118 patients (72% female; mean (SD) age, 55 (13.4)) in the hydrocodone/tramadol/codeine cohort and 5,547 patients (64% female; mean (SD) age, 53.6 (14.2)) in the oxycodone cohort. Hydrocodone/tramadol/codeine‐treated patients exposed to CYP2D6‐inhibitor antidepressants (n = 7,043) had a higher crude rate of pain‐related ED visits than those taking other antidepressants (n = 5,075) (3.28% vs. 1.87%), with an adjusted odds ratio (aOR) of 1.75 (95% CI: 1.36 to 2.24). Similarly, in the oxycodone cohort, CYP2D6‐inhibitor antidepressant‐exposed individuals (n = 3,206) had a higher crude rate of ED visits than individuals exposed to other antidepressants (n = 2,341) (5.02% vs. 3.37%), with aOR of 1.70 (95% CI: 1.27–2.27). Similar findings were observed in secondary and sensitivity analyses. Our findings suggest patients with concomitant use of hydrocodone/tramadol/codeine or oxycodone and CYP2D6 inhibitors have more frequent ED visits for pain, which may be due to inadequate pain control. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Radiomics-Derived Brain Age Predicts Functional Outcome After Acute Ischemic Stroke

Author

Bretzner, Martin, Bonkhoff, Anna K, Schirmer, Markus D., Hong, Sungmin, Dalca, Adrian, Donahue, Kathleen, Giese, Anne-Katrin, Etherton, Mark R, Rist, Pamela M, Nardin, Marco, Regenhardt, Robert W, Leclerc, Xavier, Lopes, Renaud, Gautherot, Morgan, Wang, Clinton, Benavente, Oscar R, Cole, John W., Donatti, Amanda, Griessenauer, Christoph, Heitsch, Laura, Holmegaard, Lukas, Jood, Katarina, Jimenez-Conde, Jordi, Kittner, Steven J, Lemmens, Robin, Levi, Christopher R, McArdle, Patrick F, McDonough, Caitrin W., Meschia, James F, Phuah, Chia-Ling, Rolfs, Arndt, Ropele, Stefan, Rosand, Jonathan, Roquer, Jaume, Rundek, Tatjana, Sacco, Ralph L., Schmidt, Reinhold, Sharma, Pankaj, Slowik, Agnieszka, Sousa, Alessandro, Stanne, Tara M, Strbian, Daniel, Tatlisumak, Turgut, Thijs, Vincent, Vagal, Achala, Wasselius, Johan, Woo, Daniel, Wu, Ona, Zand, Ramin, Worrall, Bradford B, Maguire, Jane, Lindgren, Arne G, Jern, Christina, Golland, Polina, Kuchcinski, Grégory, and Rost, Natalia S

Published
2022
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8. Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke

Author

Jaworek, Thomas, Xu, Huichun, Gaynor, Brady J, Cole, John W., Rannikmae, Kristiina, Stanne, Tara M, Tomppo, Liisa, Abedi, Vida, Amouyel, Philippe, Armstrong, Nicole D, Attia, John, Bell, Steven, Benavente, Oscar R, Boncoraglio, Giorgio B, Butterworth, Adam, Carcel-Marquez, Jara, Chen, Zhengming, Chong, Michael, Cruchaga, Carlos, Cushman, Mary, Danesh, John, Debette, Stephanie, Duggan, David J, Durda, Jon Peter, Engstrom, Gunnar, Enzinger, Chris, Faul, Jessica D, Fecteau, Natalie S, Fernandez-Cadenas, Israel, Gieger, Christian, Giese, Anne-Katrin, Grewal, Raji P, Grittner, Ulrike, Havulinna, Aki S, Heitsch, Laura, Hochberg, Marc C, Holliday, Elizabeth, Hu, Jie, Ilinca, Andreea, Irvin, Marguerite R, Jackson, Rebecca D, Jacob, Mina A., Janssen, Raquel Rabionet, Jimenez-Conde, Jordi, Johnson, Julie A, Kamatani, Yoichiro, Kardia, Sharon L, Koido, Masaru, Kubo, Michiaki, Lange, Leslie, Lee, Jin-Moo, Lemmens, Robin, Levi, Christopher R, Li, Jiang, Li, Liming, Lin, Kuang, Lopez, Haley, Luke, Sothear, Maguire, Jane, McArdle, Patrick F, McDonough, Caitrin W., Meschia, James F, Metso, Tiina, Muller-Nurasyid, Martina, OʼConnor, Timothy D, OʼDonnell, Martin, Peddareddygari, Leema R, Pera, Joanna, Perry, James A, Peters, Annette, Putaala, Jukka, Ray, Debashree, Rexrode, Kathryn, Ribases, Marta, Rosand, Jonathan, Rothwell, Peter M, Rundek, Tatjana, Ryan, Kathleen A, Sacco, Ralph L., Salomaa, Veikko, Sanchez-Mora, Cristina, Schmidt, Reinhold, Sharma, Pankaj, Slowik, Agnieszka, Smith, Jennifer A, Smith, Nicholas L, Wassertheil-Smoller, Sylvia, Soederholm, Martin, Stine, O. C, Strbian, Daniel, Sudlow, Cathie L, Tatlisumak, Turgut, Terao, Chikashi, Thijs, Vincent, Torres-Aguila, Nuria P, Tregouet, David-Alexandre, Tuladhar, Anil M., Veldink, Jan H, Walters, Robin G, Weir, David R, Woo, Daniel, Worrall, Bradford B, Hong, Charles C, Ross, Owen, Zand, Ramin, Leeuw, Frank-Erik de, Lindgren, Arne G, Pare, Guillaume, Anderson, Christopher D., Markus, Hugh S, Jern, Christina, Malik, Rainer, Dichgans, Martin, Mitchell, Braxton D, and Kittner, Steven J

Published
2022
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9. Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome

Author

Bonkhoff, Anna K, Hong, Sungmin, Bretzner, Martin, Schirmer, Markus D., Regenhardt, Robert W, Arsava, E. Murat, Donahue, Kathleen, Nardin, Marco, Dalca, Adrian, Giese, Anne-Katrin, Etherton, Mark R, Hancock, Brandon L., Mocking, Steven J.T., McIntosh, Elissa, Attia, John, Benavente, Oscar, Cole, John W., Donatti, Amanda, Griessenauer, Christoph, Heitsch, Laura, Holmegaard, Lukas, Jood, Katarina, Jimenez-Conde, Jordi, Kittner, Steven, Lemmens, Robin, Levi, Christopher, McDonough, Caitrin W., Meschia, James, Phuah, Chia-Ling, Rolfs, Arndt, Ropele, Stefan, Rosand, Jonathan, Roquer, Jaume, Rundek, Tatjana, Sacco, Ralph L., Schmidt, Reinhold, Sharma, Pankaj, Slowik, Agnieszka, Soederholm, Martin, Sousa, Alessandro, Stanne, Tara M, Strbian, Daniel, Tatlisumak, Turgut, Thijs, Vincent, Vagal, Achala, Wasselius, Johan, Woo, Daniel, Zand, Ramin, McArdle, Patrick, Worrall, Bradford B, Jern, Christina, Lindgren, Arne G, Maguire, Jane, Golland, Polina, Bzdok, Danilo, Wu, Ona, and Rost, Natalia S

Published
2022
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10. Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry – Informing optimal antiplatelet strategies.

Author

Cavallari, Larisa H., Lee, Craig R., Franchi, Francesco, Keeley, Ellen C., Rossi, Joseph S., Thomas, Cameron D., Gong, Yan, McDonough, Caitrin W., Starostik, Petr, Al Saeed, Maryam J., Been, Latonya, Kulick, Natasha, Malave, Jean, Mulrenin, Ian R., Nguyen, Anh B., Terrell, Joshua N., Tillotson, Grace, Beitelshees, Amber L., Winterstein, Almut G., and Stouffer, George A.

Subjects
PLATELET aggregation inhibitors, PERCUTANEOUS coronary intervention, PLATELET function tests, CYTOCHROME P-450 CYP2C19, PRASUGREL
Abstract

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no‐function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no‐function allele carriers. However, the influence of patient‐specific demographic, clinical, and other genetic factors on outcomes with genotype‐guided DAPT has not been defined. In addition, the impact of genotype‐guided de‐escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no‐function allele has not been investigated in a diverse, real‐world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient‐specific factors on clinical outcomes with CYP2C19‐guided DAPT, evaluate the safety and effectiveness of CYP2C19‐guided DAPT de‐escalation following PCI in a real‐world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real‐world population. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Using electronic health records for clinical pharmacology research: Challenges and considerations.

Author

Jafari, Eissa, Blackman, Marisa H., Karnes, Jason H., Van Driest, Sara L., Crawford, Dana C., Choi, Leena, and McDonough, Caitrin W.

Subjects
ELECTRONIC health records, CLINICAL pharmacology, DRUG side effects, MEDICAL research, NATURAL language processing, DATA structures
Abstract

Electronic health records (EHRs) contain a vast array of phenotypic data on large numbers of individuals, often collected over decades. Due to the wealth of information, EHR data have emerged as a powerful resource to make first discoveries and identify disparities in our healthcare system. While the number of EHR‐based studies has exploded in recent years, most of these studies are directed at associations with disease rather than pharmacotherapeutic outcomes, such as drug response or adverse drug reactions. This is largely due to challenges specific to deriving drug‐related phenotypes from the EHR. There is great potential for EHR‐based discovery in clinical pharmacology research, and there is a critical need to address specific challenges related to accurate and reproducible derivation of drug‐related phenotypes from the EHR. This review provides a detailed evaluation of challenges and considerations for deriving drug‐related data from EHRs. We provide an examination of EHR‐based computable phenotypes and discuss cutting‐edge approaches to map medication information for clinical pharmacology research, including medication‐based computable phenotypes and natural language processing. We also discuss additional considerations such as data structure, heterogeneity and missing data, rare phenotypes, and diversity within the EHR. By further understanding the complexities associated with conducting clinical pharmacology research using EHR‐based data, investigators will be better equipped to design thoughtful studies with more reproducible results. Progress in utilizing EHRs for clinical pharmacology research should lead to significant advances in our ability to understand differential drug response and predict adverse drug reactions. [ABSTRACT FROM AUTHOR]

Published
2024
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12. CYP2C19 Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.

Author

Tunehag, Kayla R., Thomas, Cameron D., Franchi, Francesco, Rossi, Joseph S., Keeley, Ellen C., Anderson, R. David, Beitelshees, Amber L., Duarte, Julio D., Yan Gong, Kerensky, Richard A., McDonough, Caitrin W., Nguyen, Anh B., Paz, Luis Ortega, Venkatesh, Sanjay, Wang, Yehua, Johnson, Julie A., Winterstein, Almut G., Stouffer, George A., Angiolillo, Dominick J., and Cavallari, Larisa H.

Published
2024
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13. A Genetic Response Score for Hydrochlorothiazide Use

Author

Shahin, Mohamed H, Gong, Yan, McDonough, Caitrin W, Rotroff, Daniel M, Beitelshees, Amber L, Garrett, Timothy J, Gums, John G, Motsinger-Reif, Alison, Chapman, Arlene B, Turner, Stephen T, Boerwinkle, Eric, Frye, Reginald F, Fiehn, Oliver, Cooper-DeHoff, Rhonda M, Kaddurah-Daouk, Rima, and Johnson, Julie A

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Patient Safety, Biotechnology, Hypertension, Genetics, Clinical Research, Human Genome, AMP-Activated Protein Kinases, Adult, Aged, Antihypertensive Agents, Blood Pressure Monitoring, Ambulatory, Cohort Studies, DCC Receptor, Epoxide Hydrolases, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hydrochlorothiazide, Male, Metabolomics, Middle Aged, Pharmacogenetics, Polymorphism, Genetic, Prospective Studies, Receptors, Cell Surface, Severity of Illness Index, Signal Transduction, Treatment Outcome, Tumor Suppressor Proteins, White People, hydrochlorothiazide, hypertension, genome-wide association study, metabolomics, pharmacogenetics, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Hydrochlorothiazide is among the most commonly prescribed antihypertensives; yet,

Published
2016

14. Novel plasma biomarker of atenolol-induced hyperglycemia identified through a metabolomics-genomics integrative approach

Author

de Oliveira, Felipe A, Shahin, Mohamed H, Gong, Yan, McDonough, Caitrin W, Beitelshees, Amber L, Gums, John G, Chapman, Arlene B, Boerwinkle, Eric, Turner, Stephen T, Frye, Reginald F, Fiehn, Oliver, Kaddurah-Daouk, Rima, Johnson, Julie A, and Cooper-DeHoff, Rhonda M

Subjects
Medical Biochemistry and Metabolomics, Biological Sciences, Biomedical and Clinical Sciences, Genetics, Diabetes, Clinical Research, Biotechnology, Human Genome, Metabolic and endocrine, Pharmacometabolomics, Pharmacogenomics, beta-blockers, Atenolol, Hyperglycemia, beta-alanine, β-alanine, β-blockers, Analytical Chemistry, Biochemistry and Cell Biology, Clinical Sciences, Biochemistry and cell biology, Medical biochemistry and metabolomics, Analytical chemistry
Abstract

While atenolol is an effective antihypertensive agent, its use is also associated with adverse events including hyperglycemia and incident diabetes that may offset the benefits of blood pressure lowering. By combining metabolomic and genomic data acquired from hypertensive individuals treated with atenolol, it may be possible to better understand the pathways that most impact the development of an adverse glycemic state. To identify biomarkers that can help predict susceptibility to blood glucose excursions during exposure to atenolol. Plasma samples acquired from 234 Caucasian participants treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses trial were analyzed by gas chromatography Time-Of-Flight Mass Spectroscopy. Metabolomics and genomics data were integrated by first correlating participant's metabolomic profiles to change in glucose after treatment with atenolol, and then incorporating genotype information from genes involved in metabolite pathways associated with glucose response. Our findings indicate that the baseline level of β-alanine was associated with glucose change after treatment with atenolol (Q = 0.007, β = 2.97 mg/dL). Analysis of genomic data revealed that carriers of the G allele for SNP rs2669429 in gene DPYS, which codes for dihydropyrimidinase, an enzyme involved in β-alanine formation, had significantly higher glucose levels after treatment with atenolol when compared with non-carriers (Q = 0.05, β = 2.76 mg/dL). This finding was replicated in participants who received atenolol as an add-on therapy (P = 0.04, β = 1.86 mg/dL). These results suggest that β-alanine and rs2669429 may be predictors of atenolol-induced hyperglycemia in Caucasian individuals and further investigation is warranted.

Published
2016

15. Whole genome sequence analysis of apparent treatment resistant hypertension status in participants from the Trans-Omics for Precision Medicine program

Author

Armstrong, Nicole D., primary, Srinivasasainagendra, Vinodh, additional, Ammous, Farah, additional, Assimes, Themistocles L., additional, Beitelshees, Amber L., additional, Brody, Jennifer, additional, Cade, Brian E., additional, Ida Chen, Yii-Der, additional, Chen, Han, additional, de Vries, Paul S., additional, Floyd, James S., additional, Franceschini, Nora, additional, Guo, Xiuqing, additional, Hellwege, Jacklyn N., additional, House, John S., additional, Hwu, Chii-Min, additional, Kardia, Sharon L. R., additional, Lange, Ethan M., additional, Lange, Leslie A., additional, McDonough, Caitrin W., additional, Montasser, May E., additional, O’Connell, Jeffrey R., additional, Shuey, Megan M., additional, Sun, Xiao, additional, Tanner, Rikki M., additional, Wang, Zhe, additional, Zhao, Wei, additional, Carson, April P., additional, Edwards, Todd L., additional, Kelly, Tanika N., additional, Kenny, Eimear E., additional, Kooperberg, Charles, additional, Loos, Ruth J. F., additional, Morrison, Alanna C., additional, Motsinger-Reif, Alison, additional, Psaty, Bruce M., additional, Rao, Dabeeru C., additional, Redline, Susan, additional, Rich, Stephen S., additional, Rotter, Jerome I., additional, Smith, Jennifer A., additional, Smith, Albert V., additional, Irvin, Marguerite R., additional, and Arnett, Donna K., additional

Published
2023
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18. Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention

Author

Cavallari, Larisa H., Lee, Craig R., Beitelshees, Amber L., Cooper-DeHoff, Rhonda M., Duarte, Julio D., Voora, Deepak, Kimmel, Stephen E., McDonough, Caitrin W., Gong, Yan, Dave, Chintan V., Pratt, Victoria M., Alestock, Tameka D., Anderson, R. David, Alsip, Jorge, Ardati, Amer K., Brott, Brigitta C., Brown, Lawrence, Chumnumwat, Supatat, Clare-Salzler, Michael J., Coons, James C., Denny, Joshua C., Dillon, Chrisly, Elsey, Amanda R., Hamadeh, Issam S., Harada, Shuko, Hillegass, William B., Hines, Lindsay, Horenstein, Richard B., Howell, Lucius A., Jeng, Linda J.B., Kelemen, Mark D., Lee, Yee Ming, Magvanjav, Oyunbileg, Montasser, May, Nelson, David R., Nutescu, Edith A., Nwaba, Devon C., Pakyz, Ruth E., Palmer, Kathleen, Peterson, Josh F., Pollin, Toni I., Quinn, Alison H., Robinson, Shawn W., Schub, Jamie, Skaar, Todd C., Smith, D. Max, Sriramoju, Vindhya B., Starostik, Petr, Stys, Tomasz P., Stevenson, James M., Varunok, Nicholas, Vesely, Mark R., Wake, Dyson T., Weck, Karen E., Weitzel, Kristin W., Wilke, Russell A., Willig, James, Zhao, Richard Y., Kreutz, Rolf P., Stouffer, George A., Empey, Philip E., Limdi, Nita A., Shuldiner, Alan R., Winterstein, Almut G., and Johnson, Julie A.

Published
2018
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19. 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

20. Genome-wide association analysis of common genetic variants of resistant hypertension

Author

El Rouby, Nihal, McDonough, Caitrin W., Gong, Yan, McClure, Leslie A., Mitchell, Braxton D., Horenstein, Richard B., Talbert, Robert L., Crawford, Dana C., on behalf of eMERGE network, Gitzendanner, Matthew A., Takahashi, Atsushi, Tanaka, Toshihiro, Kubo, Michiaki, Pepine, Carl J., Cooper-DeHoff, Rhonda M., Benavente, Oscar R., Shuldiner, Alan R., and Johnson, Julie A.

Published
2019
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21. Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

Author

Asselbergs, Folkert W, Guo, Yiran, van Iperen, Erik PA, Sivapalaratnam, Suthesh, Tragante, Vinicius, Lanktree, Matthew B, Lange, Leslie A, Almoguera, Berta, Appelman, Yolande E, Barnard, John, Baumert, Jens, Beitelshees, Amber L, Bhangale, Tushar R, Chen, Yii-Der Ida, Gaunt, Tom R, Gong, Yan, Hopewell, Jemma C, Johnson, Toby, Kleber, Marcus E, Langaee, Taimour Y, Li, Mingyao, Li, Yun R, Liu, Kiang, McDonough, Caitrin W, Meijs, Matthijs FL, Middelberg, Rita PS, Musunuru, Kiran, Nelson, Christopher P, O’Connell, Jeffery R, Padmanabhan, Sandosh, Pankow, James S, Pankratz, Nathan, Rafelt, Suzanne, Rajagopalan, Ramakrishnan, Romaine, Simon PR, Schork, Nicholas J, Shaffer, Jonathan, Shen, Haiqing, Smith, Erin N, Tischfield, Sam E, van der Most, Peter J, van Vliet-Ostaptchouk, Jana V, Verweij, Niek, Volcik, Kelly A, Zhang, Li, Bailey, Kent R, Bailey, Kristian M, Bauer, Florianne, Boer, Jolanda MA, Braund, Peter S, Burt, Amber, Burton, Paul R, Buxbaum, Sarah G, Chen, Wei, Cooper-DeHoff, Rhonda M, Cupples, L Adrienne, deJong, Jonas S, Delles, Christian, Duggan, David, Fornage, Myriam, Furlong, Clement E, Glazer, Nicole, Gums, John G, Hastie, Claire, Holmes, Michael V, Illig, Thomas, Kirkland, Susan A, Kivimaki, Mika, Klein, Ronald, Klein, Barbara E, Kooperberg, Charles, Kottke-Marchant, Kandice, Kumari, Meena, LaCroix, Andrea Z, Mallela, Laya, Murugesan, Gurunathan, Ordovas, Jose, Ouwehand, Willem H, Post, Wendy S, Saxena, Richa, Scharnagl, Hubert, Schreiner, Pamela J, Shah, Tina, Shields, Denis C, Shimbo, Daichi, Srinivasan, Sathanur R, Stolk, Ronald P, Swerdlow, Daniel I, Taylor, Herman A, Topol, Eric J, Toskala, Elina, van Pelt, Joost L, van Setten, Jessica, Yusuf, Salim, Whittaker, John C, Zwinderman, AH, Study, LifeLines Cohort, Anand, Sonia S, Balmforth, Anthony J, and Berenson, Gerald S

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Human Genome, Cardiovascular, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Cholesterol, HDL, Cholesterol, LDL, Female, Genome-Wide Association Study, Genotype, Humans, Lipids, Male, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Factors, Triglycerides, White People, LifeLines Cohort Study, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.

Published
2012

22. A genome-wide association search for type 2 diabetes genes in African Americans.

Author

Palmer, Nicholette D, McDonough, Caitrin W, Hicks, Pamela J, Roh, Bong H, Wing, Maria R, An, S Sandy, Hester, Jessica M, Cooke, Jessica N, Bostrom, Meredith A, Rudock, Megan E, Talbert, Matthew E, Lewis, Joshua P, DIAGRAM Consortium, MAGIC Investigators, Ferrara, Assiamira, Lu, Lingyi, Ziegler, Julie T, Sale, Michele M, Divers, Jasmin, Shriner, Daniel, Adeyemo, Adebowale, Rotimi, Charles N, Ng, Maggie CY, Langefeld, Carl D, Freedman, Barry I, Bowden, Donald W, Voight, Benjamin F, Scott, Laura J, Steinthorsdottir, Valgerdur, Morris, Andrew P, Dina, Christian, Welch, Ryan P, Zeggini, Eleftheria, Huth, Cornelia, Aulchenko, Yurii S, Thorleifsson, Gudmar, McCulloch, Laura J, Ferreira, Teresa, Grallert, Harald, Amin, Najaf, Wu, Guanming, Willer, Cristen J, Raychaudhuri, Soumya, McCarroll, Steve A, Langenberg, Claudia, Hofmann, Oliver M, Dupuis, Josée, Qi, Lu, Segrè, Ayellet V, van Hoek, Mandy, Navarro, Pau, Ardlie, Kristin, Balkau, Beverley, Benediktsson, Rafn, Bennett, Amanda J, Blagieva, Roza, Boerwinkle, Eric, Bonnycastle, Lori L, Boström, Kristina Bengtsson, Bravenboer, Bert, Bumpstead, Suzannah, Burtt, Noël P, Charpentier, Guillaume, Chines, Peter S, Cornelis, Marilyn, Couper, David J, Crawford, Gabe, Doney, Alex SF, Elliott, Katherine S, Elliott, Amanda L, Erdos, Michael R, Fox, Caroline S, Franklin, Christopher S, Ganser, Martha, Gieger, Christian, Grarup, Niels, Green, Todd, Griffin, Simon, Groves, Christopher J, Guiducci, Candace, Hadjadj, Samy, Hassanali, Neelam, Herder, Christian, Isomaa, Bo, Jackson, Anne U, Johnson, Paul RV, Jørgensen, Torben, Kao, Wen HL, Klopp, Norman, Kong, Augustine, Kraft, Peter, Kuusisto, Johanna, Lauritzen, Torsten, Li, Man, Lieverse, Aloysius, Lindgren, Cecilia M, Lyssenko, Valeriya, Marre, Michel, Meitinger, Thomas, and Midthjell, Kristian

Subjects
DIAGRAM Consortium, MAGIC Investigators, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Case-Control Studies, Cohort Studies, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, African Americans, Female, Male, Meta-Analysis as Topic, Validation Studies as Topic, Genome-Wide Association Study, Diabetes Mellitus, Type 2, Polymorphism, Single Nucleotide, General Science & Technology
Abstract

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P

Published
2012

23. Characteristics and Predictors of Apparent Treatment-Resistant Hypertension in Real-World Populations Using Electronic Health Record-Based Data.

Author

Jafari, Eissa, Cooper-DeHoff, Rhonda M, Effron, Mark B, Hogan, William R, and McDonough, Caitrin W

Subjects
MEDICAL personnel, BLOOD pressure, HYPERTENSION, ELECTRONIC health records, CHRONIC kidney failure
Abstract

BACKGROUND Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled blood pressure (BP) despite using ≥3 antihypertensive classes or controlled BP while using ≥4 antihypertensive classes. Patients with aTRH have a higher risk for adverse cardiovascular outcomes compared with patients with controlled hypertension (HTN). Although there have been prior reports on the prevalence, characteristics, and predictors of aTRH, these have been broadly derived from smaller datasets, randomized controlled trials, or closed healthcare systems. METHODS We extracted patients with HTN defined by ICD-9 and ICD-10 codes during 1/1/2015–12/31/2018, from 2 large electronic health record databases: the OneFlorida Data Trust (n = 223,384) and Research Action for Health Network (REACHnet) (n = 175,229). We applied our previously validated aTRH and stable controlled HTN computable phenotype algorithms and performed univariate and multivariate analyses to identify the prevalence, characteristics, and predictors of aTRH in these populations. RESULTS The prevalence of aTRH among patients with HTN in OneFlorida (16.7%) and REACHnet (11.3%) was similar to prior reports. Both populations had a significantly higher proportion of Black patients with aTRH compared with those with stable controlled HTN. aTRH in both populations shared similar significant predictors, including Black race, diabetes, heart failure, chronic kidney disease, cardiomegaly, and higher body mass index. In both populations, aTRH was significantly associated with similar comorbidities, when compared with stable controlled HTN. CONCLUSIONS In 2 large, diverse real-world populations, we observed similar comorbidities and predictors of aTRH as prior studies. In the future, these results may be used to improve healthcare professionals' understanding of aTRH predictors and associated comorbidities. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Developing a common framework for evaluating the implementation of genomic medicine interventions in clinical care: the IGNITE Network’s Common Measures Working Group

Author

Orlando, Lori A, Sperber, Nina R, Voils, Corrine, Nichols, Marshall, Myers, Rachel A, Wu, R Ryanne, Rakhra-Burris, Tejinder, Levy, Kenneth D, Levy, Mia, Pollin, Toni I, Guan, Yue, Horowitz, Carol R, Ramos, Michelle, Kimmel, Stephen E, McDonough, Caitrin W, Madden, Ebony B, and Damschroder, Laura J

Published
2018
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30. Deep profiling of multiple ischemic lesions in a large, multi-center cohort: Frequency, spatial distribution, and associations to clinical characteristics

Author

Bonkhoff, Anna K., primary, Ullberg, Teresa, additional, Bretzner, Martin, additional, Hong, Sungmin, additional, Schirmer, Markus D., additional, Regenhardt, Robert W., additional, Donahue, Kathleen L., additional, Nardin, Marco J., additional, Dalca, Adrian V., additional, Giese, Anne-Katrin, additional, Etherton, Mark R., additional, Hancock, Brandon L., additional, Mocking, Steven J. T., additional, McIntosh, Elissa C., additional, Attia, John, additional, Cole, John W., additional, Donatti, Amanda, additional, Griessenauer, Christoph J., additional, Heitsch, Laura, additional, Holmegaard, Lukas, additional, Jood, Katarina, additional, Jimenez-Conde, Jordi, additional, Kittner, Steven J., additional, Lemmens, Robin, additional, Levi, Christopher R., additional, McDonough, Caitrin W., additional, Meschia, James F., additional, Phuah, Chia-Ling, additional, Ropele, Stefan, additional, Rosand, Jonathan, additional, Roquer, Jaume, additional, Rundek, Tatjana, additional, Sacco, Ralph L., additional, Schmidt, Reinhold, additional, Sharma, Pankaj, additional, Slowik, Agnieszka, additional, Sousa, Alessandro, additional, Stanne, Tara M., additional, Strbian, Daniel, additional, Tatlisumak, Turgut, additional, Thijs, Vincent, additional, Vagal, Achala, additional, Woo, Daniel, additional, Zand, Ramin, additional, McArdle, Patrick F., additional, Worrall, Bradford B., additional, Jern, Christina, additional, Lindgren, Arne G., additional, Maguire, Jane, additional, Wu, Ona, additional, Frid, Petrea, additional, Rost, Natalia S., additional, and Wasselius, Johan, additional

Published
2022
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32. Genetic Contributors of Efficacy and Adverse Metabolic Effects of Chlorthalidone in African Americans from the Genetics of Hypertension Associated Treatments (GenHAT) Study

Author

Armstrong, Nicole D., primary, Srinivasasainagendra, Vinodh, additional, Chekka, Lakshmi Manasa S., additional, Nguyen, Nam H. K., additional, Nahid, Noor A., additional, Jones, Alana C., additional, Tanner, Rikki M., additional, Hidalgo, Bertha A., additional, Limdi, Nita A., additional, Claas, Steven A., additional, Gong, Yan, additional, McDonough, Caitrin W., additional, Cooper-DeHoff, Rhonda M., additional, Johnson, Julie A., additional, Tiwari, Hemant K., additional, Arnett, Donna K., additional, and Irvin, Marguerite R., additional

Published
2022
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33. Sex-specific lesion pattern of functional outcomes after stroke

Author

Bonkhoff, Anna K., Bretzner, Martin, Hong, Sungmin, Schirmer, Markus D., Cohen, Alexander, Regenhardt, Robert W., Donahue, Kathleen L., Nardin, Marco J., Dalca, Adrian Vasile, Giese, Anne-Katrin, Etherton, Mark R., Hancock, Brandon L., Mocking, Steven J. T., McIntosh, Elissa C., Attia, John, Benavente, Oscar R., Bevan, Stephen, Cole, John W., Donatti, Amanda, Griessenauer, Christoph J., Heitsch, Laura, Holmegaard, Lukas, Jood, Katarina, Jimenez-Conde, Jordi, Kittner, Steven J., Lemmens, Robin, Levi, Christopher R., McDonough, Caitrin W., Meschia, James F., Phuah, Chia-Ling, Rolfs, Arndt, Ropele, Stefan, Rosand, Jonathan, Roquer, Jaume, Rundek, Tatjana, Sacco, Ralph L., Schmidt, Reinhold, Sharma, Pankaj, Slowik, Agnieszka, Söderholm, Martin, Sousa, Alessandro, Stanne, Tara M., Strbian, Daniel, Tatlisumak, Turgut, Thijs, Vincent, Vagal, Achala, Wasselius, Johan, Woo, Daniel, Zand, Ramin, McArdle, Patrick F., Worrall, Bradford B., Jern, Christina, Lindgren, Arne G., Maguire, Jane, Fox, Michael D., Bzdok, Danilo, Wu, Ona, Rost, Natalia S., Universitat Autònoma de Barcelona, Neurologian yksikkö, and HUS Neurocenter

Subjects
sex differences, Science & Technology, AREA, General Engineering, 3112 Neurosciences, Clinical Neurology, Neurosciences, lesion patterns, 3124 Neurology and psychiatry, functional outcomes, Bayesian hierarchical modelling, Neurosciences & Neurology, HUMAN CEREBRAL-CORTEX, Life Sciences & Biomedicine, acute ischaemic stroke
Abstract

Relying on neuroimaging and clinical data of 822 acute stroke patients, Bonkhoff et al. report substantially more detrimental effects of lesions in left-hemispheric posterior circulation regions on functional outcomes in women compared to men. These findings may motivate a sex-specific clinical stroke management to improve outcomes in the longer term. Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.

Published
2022

34. Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jurgenson, Tuuli, Namba, Shinichi, Posner, Daniel C, Kamanu, Frederick K, Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K, Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C, Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Carcel-Marquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Borte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Borge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Tregouet, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjaerg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Wilson, Peter WF, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michele M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-Francois, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke JH, Kappelle, L Jaap, Esko, Tonu, Metspalu, Andres, Magi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie LM, Rannikmae, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent NS, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engstrom, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibanez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muino, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-Francois, Delavaran, Hossein, Dorr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Muller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribases, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Asgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tarraga, Carolina, Volzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Nagai, Akiko, Murakami, Yoishinori, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Volker, Uwe, de Laat, Karlijn F, van Norden, Anouk GW, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul JAM, Gons, Rob AR, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank GW, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjaer, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethum, Kathrin, Gallego-Fabrega, Cristina, Lledos, Miquel, Llucia-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Freijo, Marimar, Arenillas, Juan Francisco, Obach, Victor, Alvarez-Sabin, Jose, Molina, Carlos A, Ribo, Marc, Munoz-Narbona, Lucia, Lopez-Cancio, Elena, Millan, Monica, Diaz-Navarro, Rosa, Vives-Bauza, Cristofol, Serrano-Heras, Gemma, Segura, Tomas, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sanchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Marti-Fabregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet MJ, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Millwood, Iona Y, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna MM, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Korv, Janika, Franca, Paulo HC, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Longstreth, WT, Jung, Keum Ji, Bastarache, Lisa, Pare, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Zwart, John-Anker, Niiranen, Teemu J, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernandez-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie, Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jurgenson, Tuuli, Namba, Shinichi, Posner, Daniel C, Kamanu, Frederick K, Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K, Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C, Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Carcel-Marquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Borte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Borge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Tregouet, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjaerg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Wilson, Peter WF, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michele M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-Francois, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke JH, Kappelle, L Jaap, Esko, Tonu, Metspalu, Andres, Magi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie LM, Rannikmae, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent NS, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engstrom, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibanez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muino, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-Francois, Delavaran, Hossein, Dorr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Muller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribases, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Asgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tarraga, Carolina, Volzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Nagai, Akiko, Murakami, Yoishinori, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Volker, Uwe, de Laat, Karlijn F, van Norden, Anouk GW, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul JAM, Gons, Rob AR, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank GW, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjaer, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethum, Kathrin, Gallego-Fabrega, Cristina, Lledos, Miquel, Llucia-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Freijo, Marimar, Arenillas, Juan Francisco, Obach, Victor, Alvarez-Sabin, Jose, Molina, Carlos A, Ribo, Marc, Munoz-Narbona, Lucia, Lopez-Cancio, Elena, Millan, Monica, Diaz-Navarro, Rosa, Vives-Bauza, Cristofol, Serrano-Heras, Gemma, Segura, Tomas, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sanchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Marti-Fabregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet MJ, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Millwood, Iona Y, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna MM, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Korv, Janika, Franca, Paulo HC, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Longstreth, WT, Jung, Keum Ji, Bastarache, Lisa, Pare, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Zwart, John-Anker, Niiranen, Teemu J, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernandez-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie

Abstract

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.

Published
2022

37. Genome-Wide and Gene-Based Meta-Analyses Identify Novel Loci Influencing Blood Pressure Response to Hydrochlorothiazide

Author

Salvi, Erika, Wang, Zhiying, Rizzi, Federica, Gong, Yan, McDonough, Caitrin W., Padmanabhan, Sandosh, Hiltunen, Timo P., Lanzani, Chiara, Zaninello, Roberta, Chittani, Martina, Bailey, Kent R., Sarin, Antti-Pekka, Barcella, Matteo, Melander, Olle, Chapman, Arlene B., Manunta, Paolo, Kontula, Kimmo K., Glorioso, Nicola, Cusi, Daniele, Dominiczak, Anna F., Johnson, Julie A., Barlassina, Cristina, Boerwinkle, Eric, Cooper-DeHoff, Rhonda M., and Turner, Stephen T.

Published
2017
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38. Evaluation of Potential Racial Disparities in CYP2C19‐Guided P2Y12 Inhibitor Prescribing After Percutaneous Coronary Intervention.

Author

Cavallari, Larisa H., Limdi, Nita A., Beitelshees, Amber L., Lee, James C., Duarte, Julio D., Franchi, Francesco, Tuteja, Sony, Giri, Jay, Empey, Philip E., Kreutz, Rolf P., Skaar, Todd C., Allen, John M., Coons, James C., Gong, Yan, McDonough, Caitrin W., Stevenson, James M., Thomas, Cameron D., Johnson, Julie A., Stouffer, George A., and Angiolillo, Dominick J.

Subjects
PERCUTANEOUS coronary intervention, RACIAL inequality, BLACK people, CYTOCHROME P-450 CYP2C19, HOSPITAL admission & discharge
Abstract

Black patients suffer worse outcomes after percutaneous coronary intervention (PCI) than White patients. Inequities in antiplatelet prescribing may contribute to this health disparity. We compared P2Y12 inhibitor prescribing by race following CYP2C19 genotyping to guide antiplatelet therapy selection after PCI. Patients from 9 sites that performed clinical CYP2C19 genotyping after PCI were included. Alternative therapy (e.g., prasugrel or ticagrelor) was recommended for CYP2C19 no‐function allele carriers, in whom clopidogrel is predicted to be less effective. The primary outcome was choice of P2Y12 inhibitor (clopidogrel vs. alternative therapy) based on genotype. Of 3,342 patients included, 2,448 (73%) were White, and 659 (20%) were Black. More Black than White patients had a no‐function allele (34.3% vs. 29.7%, P = 0.024). At hospital discharge following PCI, 44.2% of Black and 44.0% of White no‐function allele carriers were prescribed alternative therapy. At the time of the last follow‐up within 12 months, numerically fewer Black (51.8%) than White (56.7%) no‐function allele carriers were prescribed alternative therapy (P = 0.190). However, the difference was not significant after accounting for other factors associated with P2Y12 inhibitor selection (odds ratio 0.79, 95% confidence interval 0.58–1.08). Alternative therapy use did not differ between Black (14.3%) and White (16.7%) patients without a no‐function allele (P = 0.232). Among real‐world patients who received CYP2C19 testing after PCI, P2Y12 inhibitor prescribing rates did not differ between Black and White patients. Our data suggest an absence of racial disparity in genotype‐guided antiplatelet prescribing among patients receiving CYP2C19 testing. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Impact of the ABCD‐GENE Score on Clopidogrel Clinical Effectiveness after PCI: A Multi‐Site, Real‐World Investigation

Author

Thomas, Cameron D., primary, Franchi, Francesco, additional, Keeley, Ellen C., additional, Rossi, Joseph S., additional, Winget, Marshall, additional, David Anderson, R., additional, Dempsey, Alyssa L., additional, Gong, Yan, additional, Gower, Megan N., additional, Kerensky, Richard A., additional, Kulick, Natasha, additional, Malave, Jean G., additional, McDonough, Caitrin W., additional, Mulrenin, Ian R., additional, Starostik, Petr, additional, Beitelshees, Amber L., additional, Johnson, Julie A., additional, Stouffer, George A., additional, Winterstein, Almut G., additional, Angiolillo, Dominick J., additional, Lee, Craig R., additional, and Cavallari, Larisa H., additional

Published
2022
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41. Sex-specific Genome Wide Association Study Of Early-onset Ischemic Stroke

Author

Tomppo, Liisa, Rannikmae, Kristiina, Stanne, Tara M., Putaala, Jukka, Strbian, Daniel, Jern, Christina, de Leeuw, Frank Erik, Cadenas, Israel Fernandez, Slowik, Agnieszka M., Boncoraglio, Giorgio, Lindgren, Arne, Conde, Jordi J., Schmidt, Reinhold, Sharma, Pankaj, Lemmens, Robin, Melander, Olle, Rothwell, Peter, Levi, Christopher, Sudlow, Catherine, Debette, Stephanie, Metso, Tiina, Pare, Guillaume, Markus, Hugh, Saleheen, Danish, Danesh, John, Zand, Ramin, Worrall, Bradford B., Meschia, James F., Rundek, Tatjana, Woo, Daniel, Lee, Jin Moo, Irvin, Marguerite R., Mcdonough, Caitrin W., Rexrode, Kathryn M., Wassertheil-Smoller, Sylvia W., Rosand, Jonathan, Gieger, Christian, Muller-Nurasyid, Martina, Salomaa, Veikko V., Kamatani, Yoichiro, Walters, Robin, Chen, Zhengming, Dichgans, Martin, Malik, Rainer, Gaynor, Brady, Cole, John, Xu, Huichun, Mitchell, Braxton D., Kittner, Steven J., Early-Onset Stroke, Consortium, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Ischemic stroke, Gender differences, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genome-wide association studies (GWAS)
Abstract

Introduction: Genetic studies of early-onset disease have been an effective strategy to identify novel pathways and drug targets generalizable also to later-onset disease. Few studies have investigated the sex-specific genetic associations with early-onset ischemic stroke even though several features of ischemic stroke differ between males and females. We hypothesized that stratifying the GWAS by sex would reveal novel stroke loci. Methods: We performed a transethnic ischemic stroke GWAS of 3,056 female cases and 4,462 male cases < 60 years-old and 16,192 and 16,048 sex-matched controls, respectively, from the Early Onset Stroke Genetics Consortium. Results: We identified a significant association in women with a locus in close proximity to TMX1, a transmembrane platelet protein that inhibits platelet function. Additionally, we identified 2 other suggestive (P < 5 x 10-6) loci in females (see Table), i.e., at APOH, which encodes beta2-glycoprotein I, an established GWAS locus for lipoprotein(a), and LRFN2 which has been previously reported to associate with obesity-related measures and type II diabetes. We observed suggestive evidence for association in males with MMP3/MMP12, a known stroke susceptibility locus. Conclusions: Despite a very modest sample size, sex-specific analyses identified suggestive associations at biologically important novel loci in females and a known stroke locus in males. Further studies of sex-specific associations in both early- and later-onset ischemic stroke are needed.

Published
2022

46. Genome‐wide Association Study Identified Chromosome 8 Locus Associated with Medication‐Related Osteonecrosis of the Jaw

Author

Yang, Guang, primary, Singh, Sonal, additional, McDonough, Caitrin W., additional, Lamba, Jatinder K., additional, Hamadeh, Issam, additional, Holliday, L. Shannon, additional, Wang, Danxin, additional, Katz, Joseph, additional, Lakatos, Peter A., additional, Balla, Bernadett, additional, Kosa, Janos P., additional, Pelliccioni, Gian Andrea, additional, Price, Douglas K., additional, Van Driest, Sara L., additional, Figg, William D., additional, Langaee, Taimour, additional, Moreb, Jan S., additional, and Gong, Yan, additional

Published
2021
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47. Adverse Cardiovascular Outcomes and Antihypertensive Treatment: A Genome‐Wide Interaction Meta‐Analysis in the International Consortium for Antihypertensive Pharmacogenomics Studies

Author

McDonough, Caitrin W., primary, Warren, Helen R., additional, Jack, John R., additional, Motsinger‐Reif, Alison A., additional, Armstrong, Nicole D., additional, Bis, Joshua C., additional, House, John S., additional, Singh, Sonal, additional, El Rouby, Nihal M., additional, Gong, Yan, additional, Mychaleckyj, Joesyf C., additional, Rotroff, Daniel M., additional, Benavente, Oscar R., additional, Caulfield, Mark J., additional, Doria, Alessandrio, additional, Pepine, Carl J., additional, Psaty, Bruce M., additional, Glorioso, Valeria, additional, Glorioso, Nicola, additional, Hiltunen, Timo P., additional, Kontula, Kimmo K., additional, Arnett, Donna K., additional, Buse, John B., additional, Irvin, Marguerite R., additional, Johnson, Julie A., additional, Munroe, Patricia B., additional, Wagner, Michael J., additional, and Cooper‐DeHoff, Rhonda M., additional

Published
2021
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49. MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes

Author

Bretzner, Martin, primary, Bonkhoff, Anna K., additional, Schirmer, Markus D., additional, Hong, Sungmin, additional, Dalca, Adrian V., additional, Donahue, Kathleen L., additional, Giese, Anne-Katrin, additional, Etherton, Mark R., additional, Rist, Pamela M., additional, Nardin, Marco, additional, Marinescu, Razvan, additional, Wang, Clinton, additional, Regenhardt, Robert W., additional, Leclerc, Xavier, additional, Lopes, Renaud, additional, Benavente, Oscar R., additional, Cole, John W., additional, Donatti, Amanda, additional, Griessenauer, Christoph J., additional, Heitsch, Laura, additional, Holmegaard, Lukas, additional, Jood, Katarina, additional, Jimenez-Conde, Jordi, additional, Kittner, Steven J., additional, Lemmens, Robin, additional, Levi, Christopher R., additional, McArdle, Patrick F., additional, McDonough, Caitrin W., additional, Meschia, James F., additional, Phuah, Chia-Ling, additional, Rolfs, Arndt, additional, Ropele, Stefan, additional, Rosand, Jonathan, additional, Roquer, Jaume, additional, Rundek, Tatjana, additional, Sacco, Ralph L., additional, Schmidt, Reinhold, additional, Sharma, Pankaj, additional, Slowik, Agnieszka, additional, Sousa, Alessandro, additional, Stanne, Tara M., additional, Strbian, Daniel, additional, Tatlisumak, Turgut, additional, Thijs, Vincent, additional, Vagal, Achala, additional, Wasselius, Johan, additional, Woo, Daniel, additional, Wu, Ona, additional, Zand, Ramin, additional, Worrall, Bradford B., additional, Maguire, Jane M., additional, Lindgren, Arne, additional, Jern, Christina, additional, Golland, Polina, additional, Kuchcinski, Grégory, additional, and Rost, Natalia S., additional

Published
2021
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