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1. Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study

Author: Chen, Hao Yu, Dina, Christian, Small, Aeron M, Shaffer, Christian M, Levinson, Rebecca T, Helgadóttir, Anna, Capoulade, Romain, Munter, Hans Markus, Martinsson, Andreas, Cairns, Benjamin J, Trudsø, Linea C, Hoekstra, Mary, Burr, Hannah A, Marsh, Thomas W, Damrauer, Scott M, Dufresne, Line, Le Scouarnec, Solena, Messika-Zeitoun, David, Ranatunga, Dilrini K, Whitmer, Rachel A, Bonnefond, Amélie, Sveinbjornsson, Garðar, Daníelsen, Ragnar, Arnar, David O, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Gudbjartsson, Daníel F, Hólm, Hilma, Ghouse, Jonas, Olesen, Morten Salling, Christensen, Alex H, Mikkelsen, Susan, Jacobsen, Rikke Louise, Dowsett, Joseph, Pedersen, Ole Birger Vesterager, Erikstrup, Christian, Ostrowski, Sisse R, Center, Regeneron Genetics, O’Donnell, Christopher J, Budoff, Matthew J, Gudnason, Vilmundur, Post, Wendy S, Rotter, Jerome I, Lathrop, Mark, Bundgaard, Henning, Johansson, Bengt, Ljungberg, Johan, Näslund, Ulf, Le Tourneau, Thierry, Smith, J Gustav, Wells, Quinn S, Söderberg, Stefan, Stefánsson, Kári, Schott, Jean-Jacques, Rader, Daniel J, Clarke, Robert, Engert, James C, and Thanassoulis, George
Subjects: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Heart Disease - Coronary Heart Disease, Prevention, Heart Disease, Cardiovascular, Genetics, Human Genome, Atherosclerosis, 2.1 Biological and endogenous factors, Humans, Genome-Wide Association Study, Adiposity, Genetic Predisposition to Disease, Aortic Valve Stenosis, Obesity, Risk Factors, Inflammation, Dyslipidemias, Apolipoproteins, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Aortic stenosis, Genome-wide association study, Mendelian randomization, Phenome-wide association study, Gene expression, Genetic risk score, Regeneron Genetics Center, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract: AimsAlthough highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS.Methods and resultsA genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS.ConclusionDyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.
Published: 2023

2. CYP2C9*2 is associated with indomethacin treatment failure for patent ductus arteriosus

Author: Rooney, Sydney R, Shelton, Elaine L, Aka, Ida, Shaffer, Christian M, Clyman, Ronald I, Dagle, John M, Ryckman, Kelli, Lewis, Tamorah R, Reese, Jeff, Van Driest, Sara L, and Kannankeril, Prince J
Subjects: Paediatrics, Biomedical and Clinical Sciences, Perinatal Period - Conditions Originating in Perinatal Period, Human Genome, Genetics, Infant Mortality, Pediatric, Clinical Research, Preterm, Low Birth Weight and Health of the Newborn, Reproductive health and childbirth, Cohort Studies, Cyclooxygenase Inhibitors, Cytochrome P-450 CYP2C9, Ductus Arteriosus, Patent, Female, Gestational Age, Humans, Indomethacin, Infant, Infant, Newborn, Infant, Premature, Male, Treatment Failure, Treatment Outcome, ductus arteriosus, genetics, indomethacin, newborn, pharmacogenomics, Medical and Health Sciences, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract: Aims: To identify clinical andgenetic factors associated with indomethacin treatment failure in preterm neonates with patent ductus arteriosus (PDA). Patients & Methods: This is a multicenter cohort study of 144 preterm infants (22-32 weeks gestational age) at three centers who received at least one treatment course of indomethacin for PDA. Indomethacin failure was defined as requiring subsequent surgical intervention. Results: In multivariate analysis, gestational age (AOR 0.76, 95% CI 0.60-0.96), surfactant use (AOR 9.77, 95% CI 1.15-83.26), and CYP2C9*2 (AOR 3.74; 95% CI 1.34-10.44) were each associated with indomethacin failure. Conclusion: Age, surfactant use, and CYP2C9*2 influence indomethacin treatment outcome in preterm infants with PDA. This combination of clinical and genetic factors may facilitate targeted indomethacin use for PDA.
Published: 2019

3. Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Author: Rhodes, Christopher J, Batai, Ken, Bleda, Marta, Haimel, Matthias, Southgate, Laura, Germain, Marine, Pauciulo, Michael W, Hadinnapola, Charaka, Aman, Jurjan, Girerd, Barbara, Arora, Amit, Knight, Jo, Hanscombe, Ken B, Karnes, Jason H, Kaakinen, Marika, Gall, Henning, Ulrich, Anna, Harbaum, Lars, Cebola, Inês, Ferrer, Jorge, Lutz, Katie, Swietlik, Emilia M, Ahmad, Ferhaan, Amouyel, Philippe, Archer, Stephen L, Argula, Rahul, Austin, Eric D, Badesch, David, Bakshi, Sahil, Barnett, Christopher, Benza, Raymond, Bhatt, Nitin, Bogaard, Harm J, Burger, Charles D, Chakinala, Murali, Church, Colin, Coghlan, John G, Condliffe, Robin, Corris, Paul A, Danesino, Cesare, Debette, Stéphanie, Elliott, C Gregory, Elwing, Jean, Eyries, Melanie, Fortin, Terry, Franke, Andre, Frantz, Robert P, Frost, Adaani, Garcia, Joe GN, Ghio, Stefano, Ghofrani, Hossein-Ardeschir, Gibbs, J Simon R, Harley, John, He, Hua, Hill, Nicholas S, Hirsch, Russel, Houweling, Arjan C, Howard, Luke S, Ivy, Dunbar, Kiely, David G, Klinger, James, Kovacs, Gabor, Lahm, Tim, Laudes, Matthias, Machado, Rajiv D, Ross, Robert V MacKenzie, Marsolo, Keith, Martin, Lisa J, Moledina, Shahin, Montani, David, Nathan, Steven D, Newnham, Michael, Olschewski, Andrea, Olschewski, Horst, Oudiz, Ronald J, Ouwehand, Willem H, Peacock, Andrew J, Pepke-Zaba, Joanna, Rehman, Zia, Robbins, Ivan, Roden, Dan M, Rosenzweig, Erika B, Saydain, Ghulam, Scelsi, Laura, Schilz, Robert, Seeger, Werner, Shaffer, Christian M, Simms, Robert W, Simon, Marc, Sitbon, Olivier, Suntharalingam, Jay, Tang, Haiyang, Tchourbanov, Alexander Y, Thenappan, Thenappan, Torres, Fernando, Toshner, Mark R, Treacy, Carmen M, Noordegraaf, Anton Vonk, Waisfisz, Quinten, and Walsworth, Anna K
Subjects: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Genetics, Human Genome, Lung, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotyping Techniques, HLA-DP alpha-Chains, HLA-DP beta-Chains, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Pulmonary Arterial Hypertension, Risk Assessment, SOXF Transcription Factors, Signal Transduction, Survival Analysis, UK NIHR BioResource Rare Diseases Consortium, UK PAH Cohort Study Consortium, US PAH Biobank Consortium, Public Health and Health Services, Other Medical and Health Sciences, Cardiovascular medicine and haematology, Clinical sciences
Abstract: BackgroundRare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.MethodsWe did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses.FindingsA locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity.InterpretationThis is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials.FundingUK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR.
Published: 2019

4. Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies

Author: Gorski, Mathias, Rasheed, Humaira, Teumer, Alexander, Thomas, Laurent F., Graham, Sarah E., Sveinbjornsson, Gardar, Winkler, Thomas W., Günther, Felix, Stark, Klaus J., Chai, Jin-Fang, Tayo, Bamidele O., Wuttke, Matthias, Li, Yong, Tin, Adrienne, Ahluwalia, Tarunveer S., Ärnlöv, Johan, Åsvold, Bjørn Olav, Bakker, Stephan J.L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Biino, Ginevra, Böhnke, Michael, Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Brumpton, Ben, Carroll, Robert J., Chaker, Layal, Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Chu, Audrey Y., Ciullo, Marina, Cocca, Massimiliano, Cook, James P., Coresh, Josef, Cusi, Daniele, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Evans, Michele K., Feitosa, Mary F., Franke, Andre, Freitag-Wolf, Sandra, Fuchsberger, Christian, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Gieger, Christian, Gudbjartsson, Daniel F., Hallan, Stein, Hamet, Pavel, Hishida, Asahi, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Holm, Hilma, Hoppmann, Anselm, Horn, Katrin, Hutri-Kähönen, Nina, Hveem, Kristian, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Karabegović, Irma, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kühnel, Brigitte, Kuusisto, Johanna, Laakso, Markku, Lange, Leslie A., Lehtimäki, Terho, Li, Man, Lieb, Wolfgang, Lind, Lars, Lindgren, Cecilia M., Loos, Ruth J.F., Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Matias-Garcia, Pamela R., Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Morris, Andrew P., Mychaleckyj, Josyf C., Nadkarni, Girish N., Naito, Mariko, Nakatochi, Masahiro, Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., Nutile, Teresa, O’Donoghue, Michelle L., O'Connell, Jeffrey, Olafsson, Isleifur, Orho-Melander, Marju, Parsa, Afshin, Pendergrass, Sarah A., Penninx, Brenda W.J.H., Pirastu, Mario, Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rheinberger, Myriam, Rice, Kenneth M., Rizzi, Federica, Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Ruggiero, Daniela, Ryan, Kathleen A., Sabanayagam, Charumathi, Salvi, Erika, Schmidt, Helena, Schmidt, Reinhold, Scholz, Markus, Schöttker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Sieber, Karsten B., Sim, Xueling, Sims, Mario, Snieder, Harold, Stanzick, Kira J., Thorsteinsdottir, Unnur, Stocker, Hannah, Strauch, Konstantin, Stringham, Heather M., Sulem, Patrick, Szymczak, Silke, Taylor, Kent D., Thio, Chris H.L., Tremblay, Johanne, Vaccargiu, Simona, van der Harst, Pim, van der Most, Peter J., Verweij, Niek, Völker, Uwe, Wakai, Kenji, Waldenberger, Melanie, Wallentin, Lars, Wallner, Stefan, Wang, Judy, Waterworth, Dawn M., White, Harvey D., Willer, Cristen J., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yerges-Armstrong, Laura M., Zimmermann, Martina, Zonderman, Alan B., Bergler, Tobias, Stefansson, Kari, Böger, Carsten A., Pattaro, Cristian, Köttgen, Anna, Kronenberg, Florian, and Heid, Iris M.
Published: 2022
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5. Genome-wide association study of platelet factor 4/heparin antibodies in heparin-induced thrombocytopenia

Author: Giles, Jason B., Steiner, Heidi E., Rollin, Jerome, Shaffer, Christian M., Momozawa, Yukihide, Mushiroda, Taisei, Inai, Chihiro, Selleng, Kathleen, Thiele, Thomas, Pouplard, Claire, Heddle, Nancy M., Kubo, Michiaki, Miller, Elise C., Martinez, Kiana L., Phillips, Elizabeth J., Warkentin, Theodore E., Gruel, Yves, Greinacher, Andreas, Roden, Dan M., and Karnes, Jason H.
Published: 2022
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6. ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia

Author: Karnes, Jason H., Rollin, Jerome, Giles, Jason B., Martinez, Kiana L., Steiner, Heidi E., Shaffer, Christian M., Momozawa, Yukihide, Inai, Chihiro, Bombin, Andrei, Shi, Mingjian, Mosley, Jonathan D., Stanaway, Ian, Selleng, Kathleen, Thiele, Thomas, Mushiroda, Taisei, Pouplard, Claire, Heddle, Nancy M., Kubo, Michiaki, Phillips, Elizabeth J., Warkentin, Theodore E., Gruel, Yves, Greinacher, Andreas, and Roden, Dan M.
Published: 2022
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7. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Author: Winkler, Thomas W., Rasheed, Humaira, Teumer, Alexander, Gorski, Mathias, Rowan, Bryce X., Stanzick, Kira J., Thomas, Laurent F., Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y., Tayo, Bamidele, Thio, Chris H. L., Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B., Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano, Wuttke, Matthias, van der Most, Peter J., Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abbas, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P. J., Zonderman, Alan B., Smith, Albert V., Oldehinkel, Albertine J., De Grandi, Alessandro, Rosenkranz, Alexander R., Franke, Andre, Teren, Andrej, Metspalu, Andres, Hicks, Andrew A., Morris, Andrew P., Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I., Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I., Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K., Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H., Ning, Boting, Penninx, Brenda W. J. H., Vanderwerff, Brett R., Psaty, Bruce M., Kammerer, Candace M., Langefeld, Carl D., Hayward, Caroline, Spracklen, Cassandra N., Robinson-Cohen, Cassianne, Hartman, Catharina A., Lindgren, Cecilia M., Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M., Schulz, Christina-Alexandra, Willer, Cristen J., Chasman, Daniel I., Gudbjartsson, Daniel F., Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J., Waterworth, Dawn M., Mascalzoni, Deborah, Mook-Kanamori, Dennis O., Reilly, Dermot F., Daw, E. Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N., Delgado, Graciela E., Montgomery, Grant W., Snieder, Harold, Campbell, Harry, White, Harvey D., Gao, He, Stringham, Heather M., Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holgen, Kramer, Holly, Rudan, Igor, Nolte, Ilja M., Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P., Wilson, James F., Halbritter, Jan, Felix, Janine F., Divers, Jasmin, Kooner, Jaspal S., Lee, Jeannette Jen-Mai, O’Connell, Jeffrey, Rotter, Jerome I., Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C., Whitfield, John B., Gaziano, John M., Marten, Jonathan, Coresh, Josef, Jonas, Jost B., Mychaleckyj, Josyf C., Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L., Endlich, Karlhans, Dittrich, Katalin, Ryan, Kathleen A., Rice, Kenneth M., Taylor, Kent D., Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lars, Wallentin, Lars, Yerges-Armstrong, Laura M., Raffield, Laura M., Phillips, Lawrence S., Launer, Lenore J., Lyytikäinen, Leo-Pekka, Lange, Leslie A., Citterio, Lorena, Klaric, Lucija, Ikram, M. Arfan, Ising, Marcus, Kleber, Marcus E., Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Markus, Perola, Markus, de Borst, Martin H., Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F., Biggs, Mary L., Wojczynski, Mary K., Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthias, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H., Stumvoll, Michael, Province, Michael A., Evans, Michele K., O’Donoghue, Michelle L., Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A., Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G., Tan, Nicholas Y. Q., Palmer, Nicholette D., Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T., Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P., Sulem, Patrick, Magnusson, Patrik K. E., Elliott, Paul, Ridker, Paul M., Hamet, Pavel, Svensson, Per O., Joshi, Peter K., Kovacs, Peter, Pramstaller, Peter P., Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z. H., Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M., Carroll, Robert J., Gansevoort, Ron T., Loos, Ruth J. F., Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A., Graham, Sarah E., Gordon, Scott D., Hwang, Shih-Jen, Kerr, Shona M., Vaccargiu, Simona, Patil, Snehal B., Hallan, Stein, Bakker, Stephan J. L., Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S., Lehtimäki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tõnu, Haller, Toomas, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmantas, Gudnason, Vilmundur, Jaddoe, Vincent W. V., Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Stark, Klaus J., Stefansson, Kari, Böger, Carsten A., Hung, Adriana M., Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, and Heid, Iris M.
Published: 2022
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8. LPA Variants are Associated with Residual Cardiovascular Risk in Patients Receiving Statins

Author: Wei, Wei-Qi, Li, Xiaohui, Feng, Qiping, Kubo, Michiaki, Kullo, Iftikhar J, Peissig, Peggy L, Karlson, Elizabeth W, Jarvik, Gail P, Lee, Ming Ta Michael, Shang, Ning, Larson, Eric A, Edwards, Todd, Shaffer, Christian M, Mosley, Jonathan D, Maeda, Shiro, Horikoshi, Momoko, Ritchie, Marylyn, Williams, Marc S, Larson, Eric B, Crosslin, David R, Bland, Harris T, Pacheco, Jennifer A, Rasmussen-Torvik, Laura J, Cronkite, David, Hripcsak, George, Cox, Nancy J, Wilke, Russell A, Stein, C Michael, Rotter, Jerome I, Momozawa, Yukihide, Roden, Dan M, Krauss, Ronald M, and Denny, Joshua C
Subjects: Human Genome, Genetics, Clinical Research, Heart Disease, Atherosclerosis, Cardiovascular, Heart Disease - Coronary Heart Disease, Aetiology, 2.1 Biological and endogenous factors, Case-Control Studies, Coronary Disease, Databases, Genetic, Dyslipidemias, Electronic Health Records, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipoprotein(a), Phenotype, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, cholesterol, coronary disease, electronic health records, hydroxymethylglutaryl-CoA, LDL reductase inhibitors, lysophosphatidic acid, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract: BackgroundCoronary heart disease (CHD) is a leading cause of death globally. Although therapy with statins decreases circulating levels of low-density lipoprotein cholesterol and the incidence of CHD, additional events occur despite statin therapy in some individuals. The genetic determinants of this residual cardiovascular risk remain unknown.MethodsWe performed a 2-stage genome-wide association study of CHD events during statin therapy. We first identified 3099 cases who experienced CHD events (defined as acute myocardial infarction or the need for coronary revascularization) during statin therapy and 7681 controls without CHD events during comparable intensity and duration of statin therapy from 4 sites in the Electronic Medical Records and Genomics Network. We then sought replication of candidate variants in another 160 cases and 1112 controls from a fifth Electronic Medical Records and Genomics site, which joined the network after the initial genome-wide association study. Finally, we performed a phenome-wide association study for other traits linked to the most significant locus.ResultsThe meta-analysis identified 7 single nucleotide polymorphisms at a genome-wide level of significance within the LPA/PLG locus associated with CHD events on statin treatment. The most significant association was for an intronic single nucleotide polymorphism within LPA/PLG (rs10455872; minor allele frequency, 0.069; odds ratio, 1.58; 95% confidence interval, 1.35-1.86; P=2.6×10-10). In the replication cohort, rs10455872 was also associated with CHD events (odds ratio, 1.71; 95% confidence interval, 1.14-2.57; P=0.009). The association of this single nucleotide polymorphism with CHD events was independent of statin-induced change in low-density lipoprotein cholesterol (odds ratio, 1.62; 95% confidence interval, 1.17-2.24; P=0.004) and persisted in individuals with low-density lipoprotein cholesterol ≤70 mg/dL (odds ratio, 2.43; 95% confidence interval, 1.18-4.75; P=0.015). A phenome-wide association study supported the effect of this region on coronary heart disease and did not identify noncardiovascular phenotypes.ConclusionsGenetic variations at the LPA locus are associated with CHD events during statin therapy independently of the extent of low-density lipoprotein cholesterol lowering. This finding provides support for exploring strategies targeting circulating concentrations of lipoprotein(a) to reduce CHD events in patients receiving statins.
Published: 2018

9. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Author: Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, van der Harst, Pim, Navis, Gerjan, Rots, Marianne, Snieder, Harold, Swertz, Morris, Wolffenbuttel, Bruce H.R., Wijmenga, Cisca, Abecasis, Goncalo, Baras, Aris, Cantor, Michael, Coppola, Giovanni, Economides, Aris, Lotta, Luca A., Overton, John D., Reid, Jeffrey G., Shuldiner, Alan, Beechert, Christina, Forsythe, Caitlin, Fuller, Erin D., Gu, Zhenhua, Lattari, Michael, Lopez, Alexander, Schleicher, Thomas D., Padilla, Maria Sotiropoulos, Toledo, Karina, Widom, Louis, Wolf, Sarah E., Pradhan, Manasi, Manoochehri, Kia, Ulloa, Ricardo H., Bai, Xiaodong, Balasubramanian, Suganthi, Barnard, Leland, Blumenfeld, Andrew, Eom, Gisu, Habegger, Lukas, Hawes, Alicia, Khalid, Shareef, Maxwell, Evan K., Salerno, William, Staples, Jeffrey C., Jones, Marcus B., Mitnaul, Lyndon J., Gorski, Mathias, Jung, Bettina, Li, Yong, Matias-Garcia, Pamela R., Wuttke, Matthias, Coassin, Stefan, Thio, Chris H.L., Kleber, Marcus E., Winkler, Thomas W., Wanner, Veronika, Chai, Jin-Fang, Chu, Audrey Y., Cocca, Massimiliano, Feitosa, Mary F., Ghasemi, Sahar, Hoppmann, Anselm, Horn, Katrin, Li, Man, Nutile, Teresa, Scholz, Markus, Sieber, Karsten B., Teumer, Alexander, Tin, Adrienne, Wang, Judy, Tayo, Bamidele O., Ahluwalia, Tarunveer S., Almgren, Peter, Bakker, Stephan J.L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Carroll, Robert J., Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Coresh, Josef, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Franke, Andre, Freitag-Wolf, Sandra, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Gieger, Christian, Hamet, Pavel, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Xian Foo, Valencia Hui, Hutri-Kähönen, Nina, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Kähönen, Mika, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kühnel, Brigitte, Lange, Leslie A., Lehtimäki, Terho, Lieb, Wolfgang, Loos, Ruth J.F., Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Mychaleckyj, Josyf C., Nadkarni, Girish N., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., O’Donoghue, Michelle L., Orho-Melander, Marju, Pendergrass, Sarah A., Penninx, Brenda W.J.H., Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Sabanayagam, Charumathi, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Strauch, Konstantin, Szymczak, Silke, Taylor, Kent D., Tremblay, Johanne, Chaker, Layal, van der Most, Peter J., Verweij, Niek, Völker, Uwe, Waldenberger, Melanie, Wallentin, Lars, Waterworth, Dawn M., White, Harvey D., Wilson, James G., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Yan, Wanner, Christoph, Böger, Carsten A., Köttgen, Anna, Kronenberg, Florian, Pattaro, Cristian, and Heid, Iris M.
Published: 2021
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10. Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes

Author: Mosley, Jonathan D, Shoemaker, M Benjamin, Wells, Quinn S, Darbar, Dawood, Shaffer, Christian M, Edwards, Todd L, Bastarache, Lisa, McCarty, Catherine A, Thompson, Will, Chute, Christopher G, Jarvik, Gail P, Crosslin, David R, Larson, Eric B, Kullo, Iftikhar J, Pacheco, Jennifer A, Peissig, Peggy L, Brilliant, Murray H, Linneman, James G, Witte, John S, Denny, Josh C, and Roden, Dan M
Subjects: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Atherosclerosis, Genetics, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Adolescent, Adult, Aged, Atrial Fibrillation, Body Mass Index, Case-Control Studies, Electrocardiography, Female, Genotype, Humans, Male, Metabolic Syndrome, Middle Aged, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Waist Circumference, Young Adult, PR interval, atrial fibrillation, biomarker, cardiac electrophysiology, molecular epidemiology, risk factors, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract: One potential use for the PR interval is as a biomarker of disease risk. We hypothesized that quantifying the shared genetic architectures of the PR interval and a set of clinical phenotypes would identify genetic mechanisms contributing to PR variability and identify diseases associated with a genetic predictor of PR variability. We used ECG measurements from the ARIC study (Atherosclerosis Risk in Communities; n=6731 subjects) and 63 genetically modulated diseases from the eMERGE network (Electronic Medical Records and Genomics; n=12 978). We measured pairwise genetic correlations (rG) between PR phenotypes (PR interval, PR segment, P-wave duration) and each of the 63 phenotypes. The PR segment was genetically correlated with atrial fibrillation (rG=-0.88; P=0.0009). An analysis of metabolic phenotypes in ARIC also showed that the P wave was genetically correlated with waist circumference (rG=0.47; P=0.02). A genetically predicted PR interval phenotype based on 645 714 single-nucleotide polymorphisms was associated with atrial fibrillation (odds ratio=0.89 per SD change; 95% confidence interval, 0.83-0.95; P=0.0006). The differing pattern of associations among the PR phenotypes is consistent with analyses that show that the genetic correlation between the P wave and PR segment was not significantly different from 0 (rG=-0.03 [0.16]). The genetic architecture of the PR interval comprises modulators of atrial fibrillation risk and obesity.
Published: 2017

11. Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome

Author: Van Driest, Sara L., Sleeper, Lynn A., Gelb, Bruce D., Morris, Shaine A., Dietz, Harry C., Forbus, Geoffrey A., Goldmuntz, Elizabeth, Hoskoppal, Arvind, James, Jeanne, Lee, Teresa M., Levine, Jami C., Li, Jennifer S., Loeys, Bart L., Markham, Larry W., Meester, Josephina A.N., Mital, Seema, Mosley, Jonathan D., Olson, Aaron K., Renard, Marjolijn, Shaffer, Christian M., Sharkey, Angela, Young, Luciana, Lacro, Ronald V., and Roden, Dan M.
Published: 2020
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12. Phenome-wide association analysis suggests the APOL1 linked disease spectrum primarily drives kidney-specific pathways

Author: Bajaj, Archna, Ihegword, Andrea, Qiu, Chengxiang, Small, Aeron M., Wei, Wei-Qi, Bastarache, Lisa, Feng, QiPing, Kember, Rachel L., Risman, Marjorie, Bloom, Roy D., Birtwell, David L., Williams, Heather, Shaffer, Christian M., Chen, Jinbo, Center, Regeneron Genetics, Denny, Joshua C., Rader, Daniel J., Stein, C. Michael, Damrauer, Scott M., and Susztak, Katalin
Published: 2020
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13. Heart failure and atrial tachyarrhythmia on abiraterone: A pharmacovigilance study

Author: Bretagne, Marie, Lebrun-Vignes, Bénédicte, Pariente, Antoine, Shaffer, Christian M., Malouf, Gabriel G., Dureau, Pauline, Potey, Camille, Funck-Brentano, Christian, Roden, Dan M., Moslehi, Javid J., and Salem, Joe-Elie
Published: 2020
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14. Composite CYP3A phenotypes influence tacrolimus dose-adjusted concentration in lung transplant recipients

Author: Liu, Michelle, Shaver, Ciara M., Birdwell, Kelly A., Heeney, Stephanie A., Shaffer, Christian M., and Van Driest, Sara L.
Published: 2022
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15. Identifying genetically driven clinical phenotypes using linear mixed models.

Author: Mosley, Jonathan D, Witte, John S, Larkin, Emma K, Bastarache, Lisa, Shaffer, Christian M, Karnes, Jason H, Stein, C Michael, Phillips, Elizabeth, Hebbring, Scott J, Brilliant, Murray H, Mayer, John, Ye, Zhan, Roden, Dan M, and Denny, Joshua C
Subjects: Humans, Disease, Genetic Predisposition to Disease, HLA Antigens, Genotype, Phenotype, Polymorphism, Single Nucleotide, Models, Genetic, Adult, Aged, Aged, 80 and over, Middle Aged, European Continental Ancestry Group, Female, Male, Genetic Variation, Genome-Wide Association Study, Exome, and over, Models, Genetic, Polymorphism, Single Nucleotide
Abstract: We hypothesized that generalized linear mixed models (GLMMs), which estimate the additive genetic variance underlying phenotype variability, would facilitate rapid characterization of clinical phenotypes from an electronic health record. We evaluated 1,288 phenotypes in 29,349 subjects of European ancestry with single-nucleotide polymorphism (SNP) genotyping on the Illumina Exome Beadchip. We show that genetic liability estimates are primarily driven by SNPs identified by prior genome-wide association studies and SNPs within the human leukocyte antigen (HLA) region. We identify 44 (false discovery rate q
Published: 2016

16. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Author: Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, and Schmidt, Helena
Subjects: ICBP Consortium, AGEN Consortium, CARDIOGRAM, CHARGe-Heart Failure Group, ECHOGen Consortium, Humans, Genetic Predisposition to Disease, Gene Expression Regulation, Genotype, Renal Insufficiency, Chronic, Genome-Wide Association Study, Renal Insufficiency, Chronic
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
Published: 2016

17. The genetic architecture of plasma kynurenine includes cardiometabolic disease mechanisms associated with the SH2B3 gene

Author: Bagheri, Minoo, Wang, Chuan, Shi, Mingjian, Manouchehri, Ali, Murray, Katherine T., Murphy, Matthew B., Shaffer, Christian M., Singh, Kritika, Davis, Lea K., Jarvik, Gail P., Stanaway, Ian B., Hebbring, Scott, Reilly, Muredach P., Gerszten, Robert E., Wang, Thomas J., Mosley, Jonathan D., and Ferguson, Jane F.
Published: 2021
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18. HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms

Author: Konvinse, Katherine C., Trubiano, Jason A., Pavlos, Rebecca, James, Ian, Shaffer, Christian M., Bejan, Cosmin A., Schutte, Ryan J., Ostrov, David A., Pilkinton, Mark A., Rosenbach, Misha, Zwerner, Jeffrey P., Williams, Kristina B., Bourke, Jack, Martinez, Patricia, Rwandamuriye, Francois, Chopra, Abha, Watson, Mark, Redwood, Alec J., White, Katie D., Mallal, Simon A., and Phillips, Elizabeth J.
Published: 2019
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19. Common Ancestry-Specific Ion Channel Variants Predispose to Drug-Induced Arrhythmias

Author: Wada, Yuko, Yang, Tao, Shaffer, Christian M., Daniel, Laura L., Glazer, Andrew M., Davogustto, Giovanni E., Lowery, Brandon D., Farber-Eger, Eric H., Wells, Quinn S., and Roden, Dan M.
Published: 2022
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20. Inactivating Mutations in NPC1L1 and Protection from Coronary Heart Disease

Author: Stitziel, Nathan O, Won, Hong-Hee, Morrison, Alanna C, Peloso, Gina M, Do, Ron, Lange, Leslie A, Fontanillas, Pierre, Gupta, Namrata, Duga, Stefano, Goel, Anuj, Farrall, Martin, Saleheen, Danish, Ferrario, Paola, König, Inke, Asselta, Rosanna, Merlini, Piera A, Marziliano, Nicola, Notarangelo, Maria Francesca, Schick, Ursula, Auer, Paul, Assimes, Themistocles L, Reilly, Muredach, Wilensky, Robert, Rader, Daniel J, Hovingh, G Kees, Meitinger, Thomas, Kessler, Thorsten, Kastrati, Adnan, Laugwitz, Karl-Ludwig, Siscovick, David, Rotter, Jerome I, Hazen, Stanely L, Tracy, Russell, Cresci, Sharon, Spertus, John, Jackson, Rebecca, Schwartz, Stephen M, Natarajan, Pradeep, Crosby, Jacy, Muzny, Donna, Ballantyne, Christie, Rich, Stephen S, O'Donnell, Christopher J, Abecasis, Goncalo, Sunaev, Shamil, Nickerson, Deborah A, Buring, Julie E, Ridker, Paul M, Chasman, Daniel I, Austin, Erin, Kullo, Iftikhar J, Weeke, Peter E, Shaffer, Christian M, Bastarache, Lisa A, Denny, Joshua C, Roden, Dan M, Palmer, Colin, Deloukas, Panos, Lin, Dan-Yu, Tang, Zheng-zheng, Erdmann, Jeanette, Schunkert, Heribert, Danesh, John, Marrugat, Jaume, Elosua, Roberto, Ardissino, Diego, McPherson, Ruth, Watkins, Hugh, Reiner, Alex P, Wilson, James G, Altshuler, David, Gibbs, Richard A, Lander, Eric S, Boerwinkle, Eric, Gabriel, Stacey, and Kathiresan, Sekar
Subjects: Cardiovascular, Heart Disease, Atherosclerosis, Genetics, Heart Disease - Coronary Heart Disease, 2.1 Biological and endogenous factors, Aetiology, Adult, Asian People, Black People, Case-Control Studies, Cholesterol, LDL, Coronary Disease, Exons, Female, Gene Silencing, Genotype, Humans, Male, Membrane Proteins, Membrane Transport Proteins, Middle Aged, Mutation, Protein Conformation, Risk, Sequence Analysis, DNA, Triglycerides, White People, Myocardial Infarction Genetics Consortium Investigators, Medical and Health Sciences, General & Internal Medicine
Abstract: BackgroundEzetimibe lowers plasma levels of low-density lipoprotein (LDL) cholesterol by inhibiting the activity of the Niemann-Pick C1-like 1 (NPC1L1) protein. However, whether such inhibition reduces the risk of coronary heart disease is not known. Human mutations that inactivate a gene encoding a drug target can mimic the action of an inhibitory drug and thus can be used to infer potential effects of that drug.MethodsWe sequenced the exons of NPC1L1 in 7364 patients with coronary heart disease and in 14,728 controls without such disease who were of European, African, or South Asian ancestry. We identified carriers of inactivating mutations (nonsense, splice-site, or frameshift mutations). In addition, we genotyped a specific inactivating mutation (p.Arg406X) in 22,590 patients with coronary heart disease and in 68,412 controls. We tested the association between the presence of an inactivating mutation and both plasma lipid levels and the risk of coronary heart disease.ResultsWith sequencing, we identified 15 distinct NPC1L1 inactivating mutations; approximately 1 in every 650 persons was a heterozygous carrier for 1 of these mutations. Heterozygous carriers of NPC1L1 inactivating mutations had a mean LDL cholesterol level that was 12 mg per deciliter (0.31 mmol per liter) lower than that in noncarriers (P=0.04). Carrier status was associated with a relative reduction of 53% in the risk of coronary heart disease (odds ratio for carriers, 0.47; 95% confidence interval, 0.25 to 0.87; P=0.008). In total, only 11 of 29,954 patients with coronary heart disease had an inactivating mutation (carrier frequency, 0.04%) in contrast to 71 of 83,140 controls (carrier frequency, 0.09%).ConclusionsNaturally occurring mutations that disrupt NPC1L1 function were found to be associated with reduced plasma LDL cholesterol levels and a reduced risk of coronary heart disease. (Funded by the National Institutes of Health and others.).
Published: 2014

21. Clinical Features Associated With Nascent Left Ventricular Diastolic Dysfunction in a Population Aged 40 to 55 Years

Author: Mosley, Jonathan D., Levinson, Rebecca T., Brittain, Evan L., Gupta, Deepak K., Farber-Eger, Eric, Shaffer, Christian M., Denny, Josh C., Roden, Dan M., and Wells, Quinn S.
Published: 2018
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22. The polygenic architecture of left ventricular mass mirrors the clinical epidemiology

Author: Mosley, Jonathan D., Levinson, Rebecca T., Farber-Eger, Eric, Edwards, Todd L., Hellwege, Jacklyn N., Hung, Adriana M., Giri, Ayush, Shuey, Megan M., Shaffer, Christian M., Shi, Mingjian, Brittain, Evan L., Chung, Wendy K., Kullo, Iftikhar J., Arruda-Olson, Adelaide M., Jarvik, Gail P., Larson, Eric B., Crosslin, David R., Williams, Marc S., Borthwick, Ken M., Hakonarson, Hakon, Denny, Joshua C., Wang, Thomas J., Stein, Charles M., Roden, Dan M., and Wells, Quinn S.
Published: 2020
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23. Abstract 14663: High Rate of Arrhythmia Diagnoses Following Return of Pathogenic/likely Pathogenic Variants in an Unselected Population

Author: Davogustto, Giovanni E, Glazer, Andrew, Shaffer, Christian M, Farber-Eger, Eric, Dikilitas, Ozan, Ning, Shang, Pacheco, Jennifer, Mosley, Jonathan, Van Driest, Sara, Wells, Quinn, Rinke, Lauren L, Kalash, Olivia, Wada, Yuko, Bland, Sarah, Yoneda, Zachary T, Kroncke, Brett, Iftikhar, Kullo, Jarvik, Gail P, Gordon, Adam, LARSON, eric B, Manolio, Teri A, Mirshahi, Tooraj, Luo, Jonathan, Schaid, Daniel, Namjou, Bahram, ALSAIED, Tarek, Singh, Rajbir, Singhal, Ashutosh, Ralston, James D, McNally, Elizabeth M, George, Albert, Chung, Wendy, Carrell, David S, Leppig, Kathleen A, Hakonarson, Hakon, Sleiman, Patrick, Sohn, Sunghwan, Glessner, Joseph, Denny, Joshua, Wei, Wei-Qi, Shoemaker, M. Benjamin, and Roden, Dan M
Published: 2020
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24. Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study

Author: Yu Chen, Hao, Dina, Christian, Small, Aeron M, Shaffer, Christian M, Levinson, Rebecca T, Helgadóttir, Anna, Capoulade, Romain, Munter, Hans Markus, Martinsson, Andreas, Cairns, Benjamin J, Trudsø, Linea C, Hoekstra, Mary, Burr, Hannah A, Marsh, Thomas W, Damrauer, Scott M, Dufresne, Line, Le Scouarnec, Solena, Messika-Zeitoun, David, Ranatunga, Dilrini K, Whitmer, Rachel A, Bonnefond, Amélie, Sveinbjornsson, Garðar, Daníelsen, Ragnar, Arnar, David O, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Gudbjartsson, Daníel F, Hólm, Hilma, Ghouse, Jonas, Olesen, Morten Salling, Christensen, Alex H, Mikkelsen, Susan, Jacobsen, Rikke Louise, Dowsett, Joseph, Pedersen, Ole Birger Vesterager, Erikstrup, Christian, Ostrowski, Sisse R, Regeneron Genetics Center, O'Donnell, Christopher J, Budoff, Matthew J, Gudnason, Vilmundur, Post, Wendy S, Rotter, Jerome I, Lathrop, Mark, Bundgaard, Henning, Johansson, Bengt, Ljungberg, Johan, Näslund, Ulf, Le Tourneau, Thierry, Smith, J Gustav, Wells, Quinn S, Söderberg, Stefan, Stefánsson, Kári, Schott, Jean-Jacques, Rader, Daniel J, Clarke, Robert, Engert, James C, and Thanassoulis, George
Subjects: Genome-wide association study, Phenome-wide association study, Clinical Sciences, Cardiorespiratory Medicine and Haematology, Cardiovascular, Risk Factors, Mendelian randomization, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Obesity, Polymorphism, Aetiology, Adiposity, Dyslipidemias, Inflammation, Aortic stenosis, Prevention, Human Genome, Aortic Valve Stenosis, Single Nucleotide, Mendelian Randomization Analysis, Regeneron Genetics Center, Genetic risk score, Apolipoproteins, Heart Disease, Cardiovascular System & Hematology, Gene expression, Genome-Wide Association Study
Abstract: AimsAlthough highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS.Methods and resultsA genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS.ConclusionDyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.
Published: 2023

25. GWAS Summary Statistics from a Global Meta-Analysis of Aortic Stenosis

Author: Chen, Hao Yu, PhD, Dina, Christian, PhD, Small, Aeron M., MD, Shaffer, Christian M., Levinson, Rebecca T., PhD, Helgadóttir, Anna, MD, PhD, Capoulade, Romain, PhD, Munter, Hans Markus, PhD, Martinsson, Andreas, MD, Cairns, Benjamin J., PhD, Trudsø, Linea C., Hoekstra, Mary, Burr, Hannah A., Marsh, Thomas W., Damrauer, Scott M., MD, Dufresne, Line, Scouarnec, Solena Le, PhD, Messika-Zeitoun, David, MD, PhD, Ranatunga, Dilrini K., Whitmer, Rachel A., PhD, Bonnefond, Amélie, PhD, Sveinbjornsson, Garðar, Daníelsen, Ragnar, MD, PhD, Arnar, David O., MD, PhD, Thorgeirsson, Gudmundur, MD, PhD, Thorsteinsdottir, Unnur, PhD, Gudbjartsson, Daníel F., PhD, Hólm, Hilma, MD, Ghouse, Jonas, MD, Olesen, Morten Salling, PhD, Christensen, Alex H., MD, Mikkelsen, Susan, MD, Jacobsen, Rikke Louise, Dowsett, Joseph, Pedersen, Ole Birger Vesterager, MD, Erikstrup, Christian, MD, Ostrowski, Sisse R., Regeneron Genetics Center, O'Donnell, Christopher J., MD, Budoff, Matthew J., MD, Gudnason, Vilmundur, MD, Post, Wendy S., MD, Rotter, Jerome I., MD, Lathrop, Mark, PhD, Bundgaard, Henning, Johansson, Bengt, MD, PhD, Ljungberg, Johan, MD, PhD, Näslund, Ulf, MD, PhD, Tourneau, Thierry Le, MD, PhD, Smith, J. Gustav, MD, Wells, Quinn S., MD, Söderberg, Stefan, MD, PhD, Stefánsson, Kári, MD, PhD, Schott, Jean-Jacques, PhD, Rader, Daniel J., MD, Clarke, Robert, MD, Engert, James C., PhD, and Thanassoulis, George
Abstract: GWAS Summary Statistics for a Global Meta-Analysis of Aortic Stenosis in the TARGET Consortium 10.5281/zenodo.7630002 This dataset contains the genome-wide association summary statistics for a Global Meta-Analysis of Aortic Stenosis. For the analysis description and included cohorts, please see Chen et al., the European Heart Journal (2023). The data are provided on an "AS-IS" basis, without warranty of any type, expressed or implied, including but not limited to any warranty as to their performance, merchantability, or fitness for any particular purpose. If investigators use these data, any and all consequences are entirely their responsibility. By downloading and using these data, you agree that you will cite the appropriate publication in any communications or publications arising directly or indirectly from these data. When using this data, please cite the paper and this repository: Chenet al., GWAS Summary Statistics for a Global Meta-Analysis of Aortic Stenosis,the European Heart Journal (2023). Zenodo.10.5281/zenodo.7630002 Column headers: CHR: Chromosome code. Not present with 'no-map' modifier. BP: Base-pair coordinate. Not present with 'no-map' modifier. SNP: Variant identifier A1: Effect Allele A2: Other Allele N_cohort: Number of valid studies for variant P: Fixed-effects meta-analysis p-value P.R.: Random-effects meta-analysis p-value OR: Fixed-effects BETA/OR estimate OR.R.: Random-effects BETA/OR estimate Q: p-value for Cochran's Q statistic I: I2 heterogeneity index (0-100 scale) N_ind: Number of individuals Fundings: Fundings for this study were obtained from the following (listed in alphabetical order): ALFEDIAM Ardix Medical Assistance Publique - Hôpitaux de Paris Association Diabète Risque Vasculaire Bayer Diagnostics Becton Dickinson British Heart Foundation British Heart Foundation Oxford Centre Canadian Institutes for Health Research Capital Regions Research Council Cardionics, Merck Santé, Novo Nordisk CNAMTS, Lilly, Novartis Pharma Cohortes Santé TGIR County Council of Västerbotten Crafoord Foundation Ellison Medical Foundation European Research Council Fédération Française de Cardiologie Fédération Française de Cardiologie, a Fondation Coeur et Recherche Fonds de Recherche du Québec - Santé. French Regional Council of Pays-de-la-Loire (VaCaRMe program) Heart and Stroke Foundation of Canada Heart Foundation of Northern Sweden. Kaiser Permanente Knut and Alice Wallenberg foundation to the Wallenberg Center La Fondation de France Medical Research Council and the University of Oxford National Center for Advancing Translational Sciences (CTSI) National Heart, Lung, and Blood Institute (NHLBI) National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) National Institutes of Health Novo Nordisk Foundation ONIVINS Robert Wood Johnson Foundation Sanofi-Aventis; by INSERM (Réseaux en Santé Publique, Interactions entre les déterminants de la santé) Skåne University Hospital Société francophone du diabète Swedish Foundation for Strategic Research Swedish Heart–Lung Foundation Swedish National Health Service Swedish Research Council The Innovation Fund Denmark Umeå University U.S. Department of Veteran Affairs Vanderbilt University Medical Center’s institutional funding Wayne and Gladys Valley Foundation &nbsp
Published: 2023
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26. CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies

Author: McGeachie, Michael J., Wu, Ann C., Tse, Sze Man, Clemmer, George L., Sordillo, Joanne, Himes, Blanca E., Lasky-Su, Jessica, Chase, Robert P., Martinez, Fernando D., Weeke, Peter, Shaffer, Christian M., Xu, Hua, Denny, Josh C., Roden, Dan M., Panettieri, Reynold A., Jr., Raby, Benjamin A., Weiss, Scott T., and Tantisira, Kelan G.
Published: 2015
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27. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Author: Teumer, Alexander, Li, Yong, Ghasemi, Sahar, Prins, Bram P., Wuttke, Matthias, Hermle, Tobias, Giri, Ayush, Sieber, Karsten B., Qiu, Chengxiang, Kirsten, Holger, Tin, Adrienne, Chu, Audrey Y., Bansal, Nisha, Feitosa, Mary F., Wang, Lihua, Chai, Jin-Fang, Cocca, Massimiliano, Fuchsberger, Christian, Gorski, Mathias, Hoppmann, Anselm, Horn, Katrin, Li, Man, Marten, Jonathan, Noce, Damia, Nutile, Teresa, Sedaghat, Sanaz, Sveinbjornsson, Gardar, Tayo, Bamidele O., van der Most, Peter J., Xu, Yizhe, Yu, Zhi, Gerstner, Lea, Ärnlöv, Johan, Bakker, Stephan J. L., Baptista, Daniela, Biggs, Mary L., Boerwinkle, Eric, Brenner, Hermann, Burkhardt, Ralph, Carroll, Robert J., Chee, Miao-Li, Chee, Miao-Ling, Chen, Mengmeng, Cheng, Ching-Yu, Cook, James P., Coresh, Josef, Corre, Tanguy, Danesh, John, de Borst, Martin H., De Grandi, Alessandro, de Mutsert, Renée, de Vries, Aiko P. J., Degenhardt, Frauke, Dittrich, Katalin, Divers, Jasmin, Eckardt, Kai-Uwe, Ehret, Georg, Endlich, Karlhans, Felix, Janine F., Franco, Oscar H., Franke, Andre, Freedman, Barry I., Freitag-Wolf, Sandra, Gansevoort, Ron T., Giedraitis, Vilmantas, Gögele, Martin, Grundner-Culemann, Franziska, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hamet, Pavel, Harris, Tamara B., Hicks, Andrew A., Holm, Hilma, Foo, Valencia Hui Xian, Hwang, Shih-Jen, Ikram, M. Arfan, Ingelsson, Erik, Jaddoe, Vincent W. V., Jakobsdottir, Johanna, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Khor, Chiea-Chuen, Kiess, Wieland, Koenig, Wolfgang, Körner, Antje, Kovacs, Peter, Kramer, Holly, Krämer, Bernhard K., Kronenberg, Florian, Lange, Leslie A., Langefeld, Carl D., Lee, Jeannette Jen-Mai, Lehtimäki, Terho, Lieb, Wolfgang, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jianjun, Loeffler, Markus, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Maranville, Joseph C., Mascalzoni, Deborah, McMullen, Barbara, Meisinger, Christa, Meitinger, Thomas, Miliku, Kozeta, Mook-Kanamori, Dennis O., Müller-Nurasyid, Martina, Mychaleckyj, Josyf C., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Noordam, Raymond, Connell, Jeffrey O’, Olafsson, Isleifur, Palmer, Nicholette D., Peters, Annette, Podgornaia, Anna I., Ponte, Belen, Poulain, Tanja, Pramstaller, Peter P., Rabelink, Ton J., Raffield, Laura M., Reilly, Dermot F., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rivadeneira, Fernando, Runz, Heiko, Ryan, Kathleen A., Sabanayagam, Charumathi, Saum, Kai-Uwe, Schöttker, Ben, Shaffer, Christian M., Shi, Yuan, Smith, Albert V., Strauch, Konstantin, Stumvoll, Michael, Sun, Benjamin B., Szymczak, Silke, Tai, E-Shyong, Tan, Nicholas Y. Q., Taylor, Kent D., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomsen, Hauke, Thorsteinsdottir, Unnur, Tönjes, Anke, Tremblay, Johanne, Uitterlinden, André G., van der Harst, Pim, Verweij, Niek, Vogelezang, Suzanne, Völker, Uwe, Waldenberger, Melanie, Wang, Chaolong, Wilson, Otis D., Wong, Charlene, Wong, Tien-Yin, Yang, Qiong, Yasuda, Masayuki, Akilesh, Shreeram, Bochud, Murielle, Böger, Carsten A., Devuyst, Olivier, Edwards, Todd L., Ho, Kevin, Morris, Andrew P., Parsa, Afshin, Pendergrass, Sarah A., Psaty, Bruce M., Rotter, Jerome I., Stefansson, Kari, Wilson, James G., Susztak, Katalin, Snieder, Harold, Heid, Iris M., Scholz, Markus, Butterworth, Adam S., Hung, Adriana M., Pattaro, Cristian, and Köttgen, Anna
Published: 2019
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28. Probing the Virtual Proteome to Identify Novel Disease Biomarkers

Author: Mosley, Jonathan D., Benson, Mark D., Smith, J. Gustav, Melander, Olle, Ngo, Debby, Shaffer, Christian M., Ferguson, Jane F., Herzig, Matthew S., McCarty, Catherine A., Chute, Christopher G., Jarvik, Gail P., Gordon, Adam S., Palmer, Melody R., Crosslin, David R., Larson, Eric B., Carrell, David S., Kullo, Iftikhar J., Pacheco, Jennifer A., Peissig, Peggy L., Brilliant, Murray H., Kitchner, Terrie E., Linneman, James G., Namjou, Bahram, Williams, Marc S., Ritchie, Marylyn D., Borthwick, Kenneth M., Kiryluk, Krzysztof, Mentch, Frank D., Sleiman, Patrick M., Karlson, Elizabeth W., Verma, Shefali S., Zhu, Yineng, Vasan, Ramachandran S., Yang, Qiong, Denny, Josh C., Roden, Dan M., Gerszten, Robert E., and Wang, Thomas J.
Published: 2018
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29. Hypogonadism as a Reversible Cause of Torsades de Pointes in Men

Author: Salem, Joe-Elie, Waintraub, Xavier, Courtillot, Carine, Shaffer, Christian M., Gandjbakhch, Estelle, Maupain, Carole, Moslehi, Javid J., Badilini, Fabio, Haroche, Julien, Gougis, Paul, Fressart, Veronique, Glazer, Andrew M., Hidden-Lucet, Francoise, Touraine, Philippe, Lebrun-Vignes, Benedicte, Roden, Dan M., Bachelot, Anne, Funck-Brentano, Christian, Bretagne, Marie, Dureau, Pauline, Saqué, Valentin, Zarhrate-Ghoul, Aida, Bourguignon, Clément, Leban, Monique, Grouthier, Virginie, and Vaglio, Martino
Published: 2018
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30. Pilot screening study of targeted genetic polymorphisms for association with seasonal influenza hospital admission

Author: Carter, Tonia C., Hebbring, Scott J., Liu, Jixia, Mosley, Jonathan D., Shaffer, Christian M., Ivacic, Lynn C., Kopitzke, Sarah, Stefanski, Elisha L., Strenn, Rob, Sundaram, Maria E., Meece, Jennifer, Brilliant, Murray H., Ferdinands, Jill M., and Belongia, Edward A.
Published: 2018
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31. Genetic Determinants of Body Mass Index and Fasting Glucose Are Mediators of Grade 1 Diastolic Dysfunction

Author: Vaitinadin, Nataraja Sarma, primary, Shi, Mingjian, additional, Shaffer, Christian M., additional, Farber‐Eger, Eric, additional, Lowery, Brandon D., additional, Agrawal, Vineet, additional, Gupta, Deepak K., additional, Roden, Dan M., additional, Wells, Quinn S., additional, and Mosley, Jonathan D., additional
Published: 2022
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32. Supplement to: Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia Investigators. Coding variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease.

Author: Stitziel, Nathan O., Stirrups, Kathleen E., Masca, Nicholas G.D., Erdmann, Jeanette, Ferrario, Paola G., König, Inke R., Weeke, Peter E., Webb, Thomas R., Auer, Paul L., Schick, Ursula M., Lu, Yingchang, Zhang, He, Dube, Marie-Pierre, Goel, Anuj, Farrall, Martin, Peloso, Gina M., Won, Hong-Hee, Do, Ron, van Iperen, Erik, Kanoni, Stavroula, Kruppa, Jochen, Mahajan, Anubha, Scott, Robert A., Willenborg, Christina, Braund, Peter S., van Capelleveen, Julian C., Doney, Alex S.F., Donnelly, Louise A., Asselta, Rosanna, Merlini, Piera A., Duga, Stefano, Marziliano, Nicola, Denny, Josh C., Shaffer, Christian M., El-Mokhtari, Nour Eddine, Franke, Andre, Gottesman, Omri, Heilmann, Stefanie, Hengstenberg, Christian, Hoffmann, Per, Holmen, Oddgeir L., Hveem, Kristian, Jansson, Jan-Håkan, Jöckel, Karl-Heinz, Kessler, Thorsten, Kriebel, Jennifer, Laugwitz, Karl L., Marouli, Eirini, Martinelli, Nicola, McCarthy, Mark I., Van Zuydam, Natalie R., Meisinger, Christa, Esko, Tõnu, Mihailov, Evelin, Escher, Stefan A., Alver, Maris, Moebus, Susanne, Morris, Andrew D., Müller-Nurasyid, Martina, Nikpay, Majid, Olivieri, Oliviero, Perreault, Louis-Philippe Lemieux, AlQarawi, Alaa, Robertson, Neil R., Akinsanya, Karen O., Reilly, Dermot F., Vogt, Thomas F., Yin, Wu, Asselbergs, Folkert W., Kooperberg, Charles, Jackson, Rebecca D., Stahl, Eli, Strauch, Konstantin, Varga, Tibor V., Waldenberger, Melanie, Zeng, Lingyao, Kraja, Aldi T., Liu, Chunyu, Ehret, Georg B., Newton-Cheh, Christopher, Chasman, Daniel I., Chowdhury, Rajiv, Ferrario, Marco, Ford, Ian, Jukema, Wouter J., Kee, Frank, Kuulasmaa, Kari, Nordestgaard, Børge G., Perola, Markus, Saleheen, Danish, Sattar, Naveed, Surendran, Praveen, Tregouet, David, Young, Robin, M. Howson, Joanna M., Butterworth, Adam S., Danesh, John, Ardissino, Diego, Bottinger, Erwin P., Erbel, Raimund, Franks, Paul W., Girelli, Domenico, Hall, Alistair S., Hovingh, Kees G., Kastrati, Adnan, Lieb, Wolfgang, Meitinger, Thomas, Kraus, William E., Shah, Svati H., McPherson, Ruth, Orho-Melander, Marju, Melander, Olle, Metspalu, Andres, Palmer, Colin N.A., Peters, Annette, Rader, Daniel J., Reilly, Muredach P., Loos, Ruth J.F., Reiner, Alex P., Roden, Dan M., Tardif, Jean-Claude, Thompson, John R., Wareham, Nicholas J., Watkins, Hugh, Willer, Cristen J., Kathiresan, Sekar, Deloukas, Panos, Samani, Nilesh J, and Schunkert, Heribert
Published: 2016

33. Abstract 19353: Genome Wide Association Studies of Heart Failure With Reduced and Preserved Ejection Fraction Point to Different Genetic Architectures

Author: Levinson, Rebecca T, Farber-Eger, Eric, Shaffer, Christian M, Mosley, Jonathan D, Roden, Dan M, and Wells, Quinn S
Published: 2017

34. Abstract 14477: Integrating Patient-Specific Cardiomyocyte Function With Population Multi-omics Identifies a Novel Arrhythmia Pathway

Author: Bersell, Kevin R, Yang, Tao, Mosley, Jonathan D, Glazer, Andrew M, Brown, Jonathan D, Campbell, Courtney M, Hong, Charles C, Wells, Quinn S, Johnson, Amanda N, Short, Laura, Blair, Marcia A, Behr, Elijah R, Petropoulou, Evmorfia, Jamshidi, Yalda, Gerszten, Rob, Benson, Mark D, Vasan, Ramachandran S, Yang, Qiong, Jarvik, Gail P, Namjou, Bahram, Shaffer, Christian M, Parikh, Shan, Sheng, Quanhu, Kannankeril, Prince J, Wang, Thomas J, Knollmann, Bjorn C, and Roden, Dan M
Published: 2017

35. Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin‐Like Receptors (KIR) Types on Heparin‐Induced Thrombocytopenia (HIT)

Author: Karnes, Jason H., Shaffer, Christian M., Cronin, Robert, Bastarache, Lisa, Gaudieri, Silvana, James, Ian, Pavlos, Rebecca, Steiner, Heidi E., Mosley, Jonathan D., Mallal, Simon, Denny, Joshua C., Phillips, Elizabeth J., and Roden, Dan M.
Published: 2017
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36. Kcnj11 Ablation Is Associated With Increased Nitro-Oxidative Stress During Ischemia-Reperfusion Injury: Implications for Human Ischemic Cardiomyopathy

Author: Zhang, Bo, Novitskaya, Tatiana, Wheeler, Debra G., Xu, Zhaobin, Chepurko, Elena, Huttinger, Ryan, He, Heng, Varadharaj, Saradhadevi, Zweier, Jay L., Song, Yanna, Xu, Meng, Harrell, Frank E., Jr, Su, Yan Ru, Absi, Tarek, Kohr, Mark J., Ziolo, Mark T., Roden, Dan M., Shaffer, Christian M., Galindo, Cristi L., Wells, Quinn S., and Gumina, Richard J.
Published: 2017
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37. Early-Onset Atrial Fibrillation and the Prevalence of Rare Variants in Cardiomyopathy and Arrhythmia Genes

Author: Yoneda, Zachary T., primary, Anderson, Katherine C., additional, Quintana, Joseph A., additional, O’Neill, Matthew J., additional, Sims, Richard A., additional, Glazer, Andrew M., additional, Shaffer, Christian M., additional, Crawford, Diane M., additional, Stricker, Thomas, additional, Ye, Fei, additional, Wells, Quinn, additional, Stevenson, Lynne W., additional, Michaud, Gregory F., additional, Darbar, Dawood, additional, Lubitz, Steven A., additional, Ellinor, Patrick T., additional, Roden, Dan M., additional, and Shoemaker, M. Benjamin, additional
Published: 2021
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38. Supplement to: Inactivating mutations in NPC1L1 and protection from coronary heart disease.

Author: Stitziel, Nathan O., Won, Hong-Hee, Morrison, Alanna C., Peloso, Gina M., Do, Ron, Lange, Leslie A., Fontanillas, Pierre, Gupta, Namrata, Duga, Stefano, Goel, Anuj, Farrall, Martin, Saleheen, Danish, Ferrario, Paola, König, Inke, Asselta, Rosanna, Merlini, Piera Angelica, Marziliano, Nicola, Notarangelo, Maria Francesca, Schick, Ursula, Auer, Paul, Assimes, Themistocles L., Reilly, Muredach, Wilensky, Robert, Rader, Daniel J., Hovingh, G. Kees, Meitinger, Thomas, Kessler, Thorsten, Kastrati, Adnan, Laugwitz, Karl-Ludwig, Siscovick, David, Rotter, Jerome I., Hazen, Stanley L., Tracy, Russell, Cresci, Sharon, Spertus, John, Jackson, Rebecca, Schwartz, Stephen M., Natarajan, Pradeep, Crosby, Jacy, Muzny, Donna, Ballantyne, Christie, Rich, Stephen S., OʼDonnell, Christopher J., Abecasis, Goncalo, Sunyaev, Shamil, Nickerson, Deborah A., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Austin, Erin, Ye, Zi, Kullo, Iftikhar J., Weeke, Peter E., Shaffer, Christian M., Bastarache, Lisa A., Denny, Joshua C., Roden, Dan M., Palmer, Colin, Deloukas, Panos, Lin, Dan-Yu, Tang, Zheng-zheng, Erdmann, Jeanette, Schunkert, Heribert, Danesh, John, Marrugat, Jaume, Elosua, Roberto, Ardissino, Diego, McPherson, Ruth, Watkins, Hugh, Reiner, Alex P., Wilson, James G., Altshuler, David, Gibbs, Richard A., Lander, Eric S., Boerwinkle, Eric, Gabriel, Stacey, and Kathiresan, Sekar
Published: 2014

39. Polygenic Risk Score to Identify Subclinical Coronary Heart Disease Risk in Young Adults

Author: Wells, Quinn S., primary, Bagheri, Minoo, additional, Aday, Aaron W., additional, Gupta, Deepak K., additional, Shaffer, Christian M., additional, Wei, Wei-Qi, additional, Vaitinadin, Nataraja Sarna, additional, Khan, Sadiya S., additional, Greenland, Philip, additional, Wang, Thomas J., additional, Stein, C. Michael, additional, Roden, Dan M., additional, and Mosley, Jonathan D., additional
Published: 2021
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40. Maternal coding variants in complement receptor 1 and spontaneous idiopathic preterm birth

Author: McElroy, Jude J., Gutman, Courtney E., Shaffer, Christian M., Busch, Tamara D., Puttonen, Hilkka, Teramo, Kari, Murray, Jeffrey C., Hallman, Mikko, and Muglia, Louis J.
Published: 2013
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41. B-PO05-026 AGE-RELATED PREVALENCE OF RARE DISEASE-ASSOCIATED VARIANTS IN 1293 PATIENTS WITH EARLY-ONSET ATRIAL FIBRILLATION

Author: Yoneda, Zachary, primary, Anderson, Katherine C., additional, Quintana, Joseph A., additional, O'Neill, Matthew J., additional, Glazer, Andrew M., additional, Shaffer, Christian M., additional, Crawford, Diane M., additional, Stricker, Thomas, additional, Wells, Quinn, additional, Stevenson, Lynne W., additional, Michaud, Gregory F., additional, Darbar, Dawood, additional, Lubitz, Steven A., additional, Ellinor, Patrick T., additional, Roden, Dan M., additional, and Shoemaker, Moore B., additional
Published: 2021
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42. Association Between a Common, Benign Genotype and Unnecessary Bone Marrow Biopsies Among African American Patients

Author: Van Driest, Sara L., primary, Abul-Husn, Noura S., additional, Glessner, Joseph T., additional, Bastarache, Lisa, additional, Nirenberg, Sharon, additional, Schildcrout, Jonathan S., additional, Eswarappa, Meghana S., additional, Belbin, Gillian M., additional, Shaffer, Christian M., additional, Mentch, Frank, additional, Connolly, John, additional, Shi, Mingjian, additional, Stein, C. Michael, additional, Roden, Dan M., additional, Hakonarson, Hakon, additional, Cox, Nancy J., additional, Borinstein, Scott C., additional, and Mosley, Jonathan D., additional
Published: 2021
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43. High-throughput framework for genetic analyses of adverse drug reactions using electronic health records

Author: Zheng, Neil S., primary, Stone, Cosby A., additional, Jiang, Lan, additional, Shaffer, Christian M., additional, Kerchberger, V. Eric, additional, Chung, Cecilia P., additional, Feng, QiPing, additional, Cox, Nancy J., additional, Stein, C. Michael, additional, Roden, Dan M., additional, Denny, Joshua C., additional, Phillips, Elizabeth J., additional, and Wei, Wei-Qi, additional
Published: 2021
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44. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Author: Gorski, Mathias, Jung, Bettina, Li, Yong, Matias-Garcia, Pamela R., Wuttke, Matthias, Coassin, Stefan, Thio, Chris H. L., Kleber, Marcus E., Winkler, Thomas W., Wanner, Veronika, Chai, Jin-Fang, Chu, Audrey Y., Cocca, Massimiliano, Feitosa, Mary F., Ghasemi, Sahar, Hoppmann, Anselm, Horn, Katrin, Li, Man, Nutile, Teresa, Scholz, Markus, Sieber, Karsten B., Teumer, Alexander, Tin, Adrienne, Wang, Judy, Tayo, Bamidele O., Ahluwalia, Tarunveer S., Almgren, Peter, Bakker, Stephan J. L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Carroll, Robert J., Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Coresh, Josef, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Franke, Andre, Freitag-Wolf, Sandra, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Gieger, Christian, Hamet, Pavel, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Xian Foo, Valencia Hui, Hutri-Kähönen, Nina, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Kähönen, Mika, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kühnel, Brigitte, Lange, Leslie A., Lehtimäki, Terho, Lieb, Wolfgang, Loos, Ruth J. F., Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Mychaleckyj, Josyf C., Nadkarni, Girish N., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., O'Donoghue, Michelle L., Orho-Melander, Marju, Pendergrass, Sarah A., Penninx, Brenda W. J. H., Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Sabanayagam, Charumathi, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Strauch, Konstantin, Szymczak, Silke, Taylor, Kent D., Tremblay, Johanne, Chaker, Layal, van der Harst, Pim, van der Most, Peter J., Verweij, Niek, Völker, Uwe, Waldenberger, Melanie, Wallentin, Lars, Waterworth, Dawn M., White, Harvey D., Wilson, James G., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Yan, Snieder, Harold, Wanner, Christoph, Böger, Carsten A., Köttgen, Anna, Kronenberg, Florian, Pattaro, Cristian, Heid, Iris M., Gorski, Mathias, Jung, Bettina, Li, Yong, Matias-Garcia, Pamela R., Wuttke, Matthias, Coassin, Stefan, Thio, Chris H. L., Kleber, Marcus E., Winkler, Thomas W., Wanner, Veronika, Chai, Jin-Fang, Chu, Audrey Y., Cocca, Massimiliano, Feitosa, Mary F., Ghasemi, Sahar, Hoppmann, Anselm, Horn, Katrin, Li, Man, Nutile, Teresa, Scholz, Markus, Sieber, Karsten B., Teumer, Alexander, Tin, Adrienne, Wang, Judy, Tayo, Bamidele O., Ahluwalia, Tarunveer S., Almgren, Peter, Bakker, Stephan J. L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Carroll, Robert J., Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Coresh, Josef, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Franke, Andre, Freitag-Wolf, Sandra, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Gieger, Christian, Hamet, Pavel, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Xian Foo, Valencia Hui, Hutri-Kähönen, Nina, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Kähönen, Mika, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kühnel, Brigitte, Lange, Leslie A., Lehtimäki, Terho, Lieb, Wolfgang, Loos, Ruth J. F., Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Mychaleckyj, Josyf C., Nadkarni, Girish N., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., O'Donoghue, Michelle L., Orho-Melander, Marju, Pendergrass, Sarah A., Penninx, Brenda W. J. H., Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Sabanayagam, Charumathi, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Strauch, Konstantin, Szymczak, Silke, Taylor, Kent D., Tremblay, Johanne, Chaker, Layal, van der Harst, Pim, van der Most, Peter J., Verweij, Niek, Völker, Uwe, Waldenberger, Melanie, Wallentin, Lars, Waterworth, Dawn M., White, Harvey D., Wilson, James G., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Yan, Snieder, Harold, Wanner, Christoph, Böger, Carsten A., Köttgen, Anna, Kronenberg, Florian, Pattaro, Cristian, and Heid, Iris M.
Abstract: Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Published: 2021
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45. Genetic Thyrotropin Regulation of Atrial Fibrillation Risk Is Mediated Through an Effect on Height

Author: Shi, Mingjian, primary, Manouchehri, Ali M, additional, Shaffer, Christian M, additional, Vaitinadin, Nataraja Sarma, additional, Hellwege, Jacklyn N, additional, Salem, Joe-Elie, additional, Davis, Lea K, additional, Simmons, Jill H, additional, Roden, Dan M, additional, Shoemaker, M Benjamin, additional, Ferguson, Jane F, additional, and Mosley, Jonathan D, additional
Published: 2021
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46. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Author: Gorski, Mathias, primary, Jung, Bettina, additional, Li, Yong, additional, Matias-Garcia, Pamela R., additional, Wuttke, Matthias, additional, Coassin, Stefan, additional, Thio, Chris H.L., additional, Kleber, Marcus E., additional, Winkler, Thomas W., additional, Wanner, Veronika, additional, Chai, Jin-Fang, additional, Chu, Audrey Y., additional, Cocca, Massimiliano, additional, Feitosa, Mary F., additional, Ghasemi, Sahar, additional, Hoppmann, Anselm, additional, Horn, Katrin, additional, Li, Man, additional, Nutile, Teresa, additional, Scholz, Markus, additional, Sieber, Karsten B., additional, Teumer, Alexander, additional, Tin, Adrienne, additional, Wang, Judy, additional, Tayo, Bamidele O., additional, Ahluwalia, Tarunveer S., additional, Almgren, Peter, additional, Bakker, Stephan J.L., additional, Banas, Bernhard, additional, Bansal, Nisha, additional, Biggs, Mary L., additional, Boerwinkle, Eric, additional, Bottinger, Erwin P., additional, Brenner, Hermann, additional, Carroll, Robert J., additional, Chalmers, John, additional, Chee, Miao-Li, additional, Chee, Miao-Ling, additional, Cheng, Ching-Yu, additional, Coresh, Josef, additional, de Borst, Martin H., additional, Degenhardt, Frauke, additional, Eckardt, Kai-Uwe, additional, Endlich, Karlhans, additional, Franke, Andre, additional, Freitag-Wolf, Sandra, additional, Gampawar, Piyush, additional, Gansevoort, Ron T., additional, Ghanbari, Mohsen, additional, Gieger, Christian, additional, Hamet, Pavel, additional, Ho, Kevin, additional, Hofer, Edith, additional, Holleczek, Bernd, additional, Xian Foo, Valencia Hui, additional, Hutri-Kähönen, Nina, additional, Hwang, Shih-Jen, additional, Ikram, M. Arfan, additional, Josyula, Navya Shilpa, additional, Kähönen, Mika, additional, Khor, Chiea-Chuen, additional, Koenig, Wolfgang, additional, Kramer, Holly, additional, Krämer, Bernhard K., additional, Kühnel, Brigitte, additional, Lange, Leslie A., additional, Lehtimäki, Terho, additional, Lieb, Wolfgang, additional, Loos, Ruth J.F., additional, Lukas, Mary Ann, additional, Lyytikäinen, Leo-Pekka, additional, Meisinger, Christa, additional, Meitinger, Thomas, additional, Melander, Olle, additional, Milaneschi, Yuri, additional, Mishra, Pashupati P., additional, Mononen, Nina, additional, Mychaleckyj, Josyf C., additional, Nadkarni, Girish N., additional, Nauck, Matthias, additional, Nikus, Kjell, additional, Ning, Boting, additional, Nolte, Ilja M., additional, O’Donoghue, Michelle L., additional, Orho-Melander, Marju, additional, Pendergrass, Sarah A., additional, Penninx, Brenda W.J.H., additional, Preuss, Michael H., additional, Psaty, Bruce M., additional, Raffield, Laura M., additional, Raitakari, Olli T., additional, Rettig, Rainer, additional, Rheinberger, Myriam, additional, Rice, Kenneth M., additional, Rosenkranz, Alexander R., additional, Rossing, Peter, additional, Rotter, Jerome I., additional, Sabanayagam, Charumathi, additional, Schmidt, Helena, additional, Schmidt, Reinhold, additional, Schöttker, Ben, additional, Schulz, Christina-Alexandra, additional, Sedaghat, Sanaz, additional, Shaffer, Christian M., additional, Strauch, Konstantin, additional, Szymczak, Silke, additional, Taylor, Kent D., additional, Tremblay, Johanne, additional, Chaker, Layal, additional, van der Harst, Pim, additional, van der Most, Peter J., additional, Verweij, Niek, additional, Völker, Uwe, additional, Waldenberger, Melanie, additional, Wallentin, Lars, additional, Waterworth, Dawn M., additional, White, Harvey D., additional, Wilson, James G., additional, Wong, Tien-Yin, additional, Woodward, Mark, additional, Yang, Qiong, additional, Yasuda, Masayuki, additional, Yerges-Armstrong, Laura M., additional, Zhang, Yan, additional, Snieder, Harold, additional, Wanner, Christoph, additional, Böger, Carsten A., additional, Köttgen, Anna, additional, Kronenberg, Florian, additional, Pattaro, Cristian, additional, Heid, Iris M., additional, Alizadeh, Behrooz Z., additional, Boezen, H. Marike, additional, Franke, Lude, additional, Navis, Gerjan, additional, Rots, Marianne, additional, Swertz, Morris, additional, Wolffenbuttel, Bruce H.R., additional, Wijmenga, Cisca, additional, Abecasis, Goncalo, additional, Baras, Aris, additional, Cantor, Michael, additional, Coppola, Giovanni, additional, Economides, Aris, additional, Lotta, Luca A., additional, Overton, John D., additional, Reid, Jeffrey G., additional, Shuldiner, Alan, additional, Beechert, Christina, additional, Forsythe, Caitlin, additional, Fuller, Erin D., additional, Gu, Zhenhua, additional, Lattari, Michael, additional, Lopez, Alexander, additional, Schleicher, Thomas D., additional, Padilla, Maria Sotiropoulos, additional, Toledo, Karina, additional, Widom, Louis, additional, Wolf, Sarah E., additional, Pradhan, Manasi, additional, Manoochehri, Kia, additional, Ulloa, Ricardo H., additional, Bai, Xiaodong, additional, Balasubramanian, Suganthi, additional, Barnard, Leland, additional, Blumenfeld, Andrew, additional, Eom, Gisu, additional, Habegger, Lukas, additional, Hawes, Alicia, additional, Khalid, Shareef, additional, Maxwell, Evan K., additional, Salerno, William, additional, Staples, Jeffrey C., additional, Jones, Marcus B., additional, and Mitnaul, Lyndon J., additional
Published: 2021
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47. Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis

Author: Chen, Hao Yu, Cairns, Benjamin J., Small, Aeron M., Burr, Hannah A., Ambikkumar, Athithan, Martinsson, Andreas, Thériault, Sébastien, Munter, Hans Markus, Steffen, Brian, Zhang, Richard, Levinson, Rebecca T., Shaffer, Christian M., Rong, Jian, Sonestedt, Emily, Dufresne, Line, Ljungberg, Johan, Näslund, Ulf, Johansson, Bengt, Ranatunga, Dilrini K., Whitmer, Rachel A., Budoff, Matthew J., Nguyen, Albert, Vasan, Ramachandran S., Larson, Martin G., Harris, William S., Damrauer, Scott M., Stark, Ken D., Boekholdt, S. Matthijs, Wareham, Nicholas J., Pibarot, Philippe, Arsenault, Benoit J., Mathieu, Patrick, Gudnason, Vilmundur, O'Donnell, Christopher J., Rotter, Jerome I., Tsai, Michael Y., Post, Wendy S., Clarke, Robert, Söderberg, Stefan, Bossé, Yohan, Wells, Quinn S., Smith, J. Gustav, Rader, Daniel J., Lathrop, Mark, Engert, James C., Thanassoulis, George, Chen, Hao Yu, Cairns, Benjamin J., Small, Aeron M., Burr, Hannah A., Ambikkumar, Athithan, Martinsson, Andreas, Thériault, Sébastien, Munter, Hans Markus, Steffen, Brian, Zhang, Richard, Levinson, Rebecca T., Shaffer, Christian M., Rong, Jian, Sonestedt, Emily, Dufresne, Line, Ljungberg, Johan, Näslund, Ulf, Johansson, Bengt, Ranatunga, Dilrini K., Whitmer, Rachel A., Budoff, Matthew J., Nguyen, Albert, Vasan, Ramachandran S., Larson, Martin G., Harris, William S., Damrauer, Scott M., Stark, Ken D., Boekholdt, S. Matthijs, Wareham, Nicholas J., Pibarot, Philippe, Arsenault, Benoit J., Mathieu, Patrick, Gudnason, Vilmundur, O'Donnell, Christopher J., Rotter, Jerome I., Tsai, Michael Y., Post, Wendy S., Clarke, Robert, Söderberg, Stefan, Bossé, Yohan, Wells, Quinn S., Smith, J. Gustav, Rader, Daniel J., Lathrop, Mark, Engert, James C., and Thanassoulis, George
Abstract: Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets. Objective: To identify novel genetic loci and pathways associated with AS. Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019. Exposures: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples. Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography. Results: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associa
Published: 2020
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48. Arrhythmia Variant Associations and Reclassifications in the eMERGE-III Sequencing Study.

Author: Glazer, Andrew M., Davogustto, Giovanni, Shaffer, Christian M., Vanoye, Carlos G., Desai, Reshma R. MS, Farber-Eger, Eric H., Dikilitas, Ozan, Shang, Ning, Pacheco, Jennifer A. BA, Yang, Tao, Muhammad, Ayesha, Mosley, Jonathan D., Van Driest, Sara L., Wells, Quinn S. PharmD, MSCI, Shaffer, Lauren Lee, Kalash, Olivia R. BA, Wada, Yuko, Bland, Sarah, Yoneda, Zachary T. MSCI, and Mitchell, Devyn W.
Published: 2022
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49. Genome-Wide Association Study Identifies Variation in ABO As Risk Factor for Platelet Reactivity in Heparin-Induced Thrombocytopenia

Author: Giles, Jason B, primary, Rollin, Jérôme, additional, Shaffer, Christian M, additional, Steiner, Heidi E, additional, Momozawa, Yukihide, additional, Stanaway, Ian, additional, Mushiroda, Taisei, additional, Pouplard, Claire, additional, Heddle, Nancy, additional, Kubo, Michiaki, additional, Phillips, Elizabeth, additional, Warkentin, Theodore E., additional, Gruel, Yves, additional, Greinacher, Andreas, additional, Roden, Dan, additional, and Karnes, Jason, additional
Published: 2020
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50. Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis

Author: Chen, Hao Yu, primary, Cairns, Benjamin J., additional, Small, Aeron M., additional, Burr, Hannah A., additional, Ambikkumar, Athithan, additional, Martinsson, Andreas, additional, Thériault, Sébastien, additional, Munter, Hans Markus, additional, Steffen, Brian, additional, Zhang, Richard, additional, Levinson, Rebecca T., additional, Shaffer, Christian M., additional, Rong, Jian, additional, Sonestedt, Emily, additional, Dufresne, Line, additional, Ljungberg, Johan, additional, Näslund, Ulf, additional, Johansson, Bengt, additional, Ranatunga, Dilrini K., additional, Whitmer, Rachel A., additional, Budoff, Matthew J., additional, Nguyen, Albert, additional, Vasan, Ramachandran S., additional, Larson, Martin G., additional, Harris, William S., additional, Damrauer, Scott M., additional, Stark, Ken D., additional, Boekholdt, S. Matthijs, additional, Wareham, Nicholas J., additional, Pibarot, Philippe, additional, Arsenault, Benoit J., additional, Mathieu, Patrick, additional, Gudnason, Vilmundur, additional, O’Donnell, Christopher J., additional, Rotter, Jerome I., additional, Tsai, Michael Y., additional, Post, Wendy S., additional, Clarke, Robert, additional, Söderberg, Stefan, additional, Bossé, Yohan, additional, Wells, Quinn S., additional, Smith, J. Gustav, additional, Rader, Daniel J., additional, Lathrop, Mark, additional, Engert, James C., additional, and Thanassoulis, George, additional
Published: 2020
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