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1. The genetic landscape of neuro-related proteins in human plasma

Author

Repetto, Linda, Chen, Jiantao, Yang, Zhijian, Zhai, Ranran, Timmers, Paul R. H. J., Feng, Xiao, Li, Ting, Yao, Yue, Maslov, Denis, Timoshchuk, Anna, Tu, Fengyu, Twait, Emma L., May-Wilson, Sebastian, Muckian, Marisa D., Prins, Bram P., Png, Grace, Kooperberg, Charles, Johansson, Åsa, Hillary, Robert F., Wheeler, Eleanor, Pan, Lu, He, Yazhou, Klasson, Sofia, Ahmad, Shahzad, Peters, James E., Gilly, Arthur, Karaleftheri, Maria, Tsafantakis, Emmanouil, Haessler, Jeffrey, Gyllensten, Ulf, Harris, Sarah E., Wareham, Nicholas J., Göteson, Andreas, Lagging, Cecilia, Ikram, Mohammad Arfan, van Duijn, Cornelia M., Jern, Christina, Landén, Mikael, Langenberg, Claudia, Deary, Ian J., Marioni, Riccardo E., Enroth, Stefan, Reiner, Alexander P., Dedoussis, George, Zeggini, Eleftheria, Sharapov, Sodbo, Aulchenko, Yurii S., Butterworth, Adam S., Mälarstig, Anders, Wilson, James F., Navarro, Pau, and Shen, Xia

Published
2024
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2. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

Author

Suzuki, Ken, Hatzikotoulas, Konstantinos, Southam, Lorraine, Taylor, Henry, Yin, Xianyong, Lorenz, Kim, Mandla, Ravi, Huerta-Chagoya, Alicia, Melloni, Giorgio, Kanoni, Stavroula, Rayner, Nigel, Bocher, Ozvan, Arruda, Ana, Sonehara, Kyuto, Namba, Shinichi, Lee, Simon, Preuss, Michael, Petty, Lauren, Schroeder, Philip, Vanderwerff, Brett, Kals, Mart, Bragg, Fiona, Lin, Kuang, Guo, Xiuqing, Zhang, Weihua, Yao, Jie, Kim, Young, Graff, Mariaelisa, Takeuchi, Fumihiko, Nano, Jana, Lamri, Amel, Nakatochi, Masahiro, Moon, Sanghoon, Scott, Robert, Cook, James, Lee, Jung-Jin, Pan, Ian, Taliun, Daniel, Parra, Esteban, Chai, Jin-Fang, Bielak, Lawrence, Tabara, Yasuharu, Hai, Yang, Thorleifsson, Gudmar, Grarup, Niels, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloé, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Kwak, Soo-Heon, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Nongmaithem, Suraj, Noordam, Raymond, Lim, Victor, Tam, Claudia, Joo, Yoonjung, Chen, Chien-Hsiun, Raffield, Laura, Prins, Bram, Nicolas, Aude, Yanek, Lisa, Chen, Guanjie, Brody, Jennifer, Kabagambe, Edmond, An, Ping, Xiang, Anny, Choi, Hyeok, Cade, Brian, Tan, Jingyi, Broadaway, K, Williamson, Alice, Kamali, Zoha, Cui, Jinrui, Thangam, Manonanthini, Adair, Linda, Adeyemo, Adebowale, Aguilar-Salinas, Carlos, Ahluwalia, Tarunveer, Anand, Sonia, Bertoni, Alain, Bork-Jensen, Jette, Brandslund, Ivan, Buchanan, Thomas, Burant, Charles, Butterworth, Adam, Canouil, Mickaël, Chan, Juliana, Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, and Cushman, Mary

Subjects
Humans, Adipocytes, Chromatin, Coronary Artery Disease, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Disease Progression, Endothelial Cells, Enteroendocrine Cells, Epigenomics, Genetic Predisposition to Disease, Genome-Wide Association Study, Islets of Langerhans, Multifactorial Inheritance, Peripheral Arterial Disease, Single-Cell Analysis
Abstract

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P

Published
2024

3. Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways

Author

Kasher, Melody, Williams, Frances MK, Freidin, Maxim B, Malkin, Ida, Cherny, Stacey S, Benjamin, Emelia, Chasman, Daniel I, Dehghan, Abbas, Ahluwalia, Tarunveer Singh, Meigs, James, Tracy, Russell, Alizadeh, Behrooz Z, Ligthart, Symen, Bis, Josh, Eiriksdottir, Gudny, Pankratz, Nathan, Gross, Myron, Rainer, Alex, Snieder, Harold, Wilson, James G, Psaty, Bruce M, Dupuis, Josee, Prins, Bram, Vaso, Urmo, Stathopoulou, Maria, Franke, Lude, Lehtimaki, Terho, Koenig, Wolfgang, Jamshidi, Yalda, Siest, Sophie, Abbasi, Ali, Uitterlinden, Andre G, Abdollahi, Mohammadreza, Schnabel, Renate, Schick, Ursula M, Nolte, Ilja M, Kraja, Aldi, Hsu, Yi-Hsiang, Tylee, Daniel S, Zwicker, Alyson, Uher, Rudolf, Davey-Smith, George, Morrison, Alanna C, Hicks, Andrew, van Duijn, Cornelia M, Ward-Caviness, Cavin, Boerwinkle, Eric, Rotter, J, Rice, Ken, Lange, Leslie, Perola, Markus, de Geus, Eco, Morris, Andrew P, Makela, Kari Matti, Stacey, David, Eriksson, Johan, Frayling, Tim M, Slagboom, Eline P, and Livshits, Gregory

Subjects
Aging, Autoimmune Disease, Arthritis, Osteoporosis, Human Genome, Heart Disease, Cardiovascular, Rheumatoid Arthritis, Genetics, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Arthritis, Rheumatoid, C-Reactive Protein, Genome-Wide Association Study, Humans, Inflammation, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, CHARGE Inflammation Working Group, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes while additionally considering an inflammatory component, C-reactive protein (CRP). Genome-wide association study summary statistics were acquired from the GEnetic Factors for OSteoporosis Consortium, Cohorts for Heart and Aging Research Consortium and UK Biobank. Mendelian randomization (MR) was used to detect the presence of causal relationships. Colocalization analysis was performed to determine shared genetic variants between CRP and OP phenotypes. Analysis of pleiotropy between traits owing to shared causal single nucleotide polymorphisms (SNPs) was performed using PL eiotropic A nalysis under CO mposite null hypothesis (PLACO). MR analysis was suggestive of horizontal pleiotropy between RA and OP traits. RA was a significant causal risk factor for CRP (β = 0.027, 95% confidence interval = 0.016-0.038). There was no evidence of CRP→OP causal relationship, but horizontal pleiotropy was apparent. Colocalization established shared genomic regions between CRP and OP, including GCKR and SERPINA1 genes. Pleiotropy arising from shared causal SNPs revealed through the colocalization analysis was all confirmed by PLACO. These genes were found to be involved in the same molecular function 'protein binding' (GO:0005515) associated with RA, OP and CRP. We identified three major components explaining the epidemiological relationship among RA, OP and inflammation: (1) Pleiotropy explains a portion of the shared genetic relationship between RA and OP, albeit polygenically; (2) RA contributes to CRP elevation and (3) CRP, which is influenced by RA, demonstrated pleiotropy with OP.

Published
2022

4. Plasma proteomic associations with genetics and health in the UK Biobank

Author

Sun, Benjamin B., Chiou, Joshua, Traylor, Matthew, Benner, Christian, Hsu, Yi-Hsiang, Richardson, Tom G., Surendran, Praveen, Mahajan, Anubha, Robins, Chloe, Vasquez-Grinnell, Steven G., Hou, Liping, Kvikstad, Erika M., Burren, Oliver S., Davitte, Jonathan, Ferber, Kyle L., Gillies, Christopher E., Hedman, Åsa K., Hu, Sile, Lin, Tinchi, Mikkilineni, Rajesh, Pendergrass, Rion K., Pickering, Corran, Prins, Bram, Baird, Denis, Chen, Chia-Yen, Ward, Lucas D., Deaton, Aimee M., Welsh, Samantha, Willis, Carissa M., Lehner, Nick, Arnold, Matthias, Wörheide, Maria A., Suhre, Karsten, Kastenmüller, Gabi, Sethi, Anurag, Cule, Madeleine, Raj, Anil, Burkitt-Gray, Lucy, Melamud, Eugene, Black, Mary Helen, Fauman, Eric B., Howson, Joanna M. M., Kang, Hyun Min, McCarthy, Mark I., Nioi, Paul, Petrovski, Slavé, Scott, Robert A., Smith, Erin N., Szalma, Sándor, Waterworth, Dawn M., Mitnaul, Lyndon J., Szustakowski, Joseph D., Gibson, Bradford W., Miller, Melissa R., and Whelan, Christopher D.

Published
2023
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5. Rare variant associations with plasma protein levels in the UK Biobank

Author

Dhindsa, Ryan S., Burren, Oliver S., Sun, Benjamin B., Prins, Bram P., Matelska, Dorota, Wheeler, Eleanor, Mitchell, Jonathan, Oerton, Erin, Hristova, Ventzislava A., Smith, Katherine R., Carss, Keren, Wasilewski, Sebastian, Harper, Andrew R., Paul, Dirk S., Fabre, Margarete A., Runz, Heiko, Viollet, Coralie, Challis, Benjamin, Platt, Adam, Vitsios, Dimitrios, Ashley, Euan A., Whelan, Christopher D., Pangalos, Menelas N., Wang, Quanli, and Petrovski, Slavé

Published
2023
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6. Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Author

Mahajan, Anubha, Spracklen, Cassandra N, Zhang, Weihua, Ng, Maggie CY, Petty, Lauren E, Kitajima, Hidetoshi, Yu, Grace Z, Rüeger, Sina, Speidel, Leo, Kim, Young Jin, Horikoshi, Momoko, Mercader, Josep M, Taliun, Daniel, Moon, Sanghoon, Kwak, Soo-Heon, Robertson, Neil R, Rayner, Nigel W, Loh, Marie, Kim, Bong-Jo, Chiou, Joshua, Miguel-Escalada, Irene, della Briotta Parolo, Pietro, Lin, Kuang, Bragg, Fiona, Preuss, Michael H, Takeuchi, Fumihiko, Nano, Jana, Guo, Xiuqing, Lamri, Amel, Nakatochi, Masahiro, Scott, Robert A, Lee, Jung-Jin, Huerta-Chagoya, Alicia, Graff, Mariaelisa, Chai, Jin-Fang, Parra, Esteban J, Yao, Jie, Bielak, Lawrence F, Tabara, Yasuharu, Hai, Yang, Steinthorsdottir, Valgerdur, Cook, James P, Kals, Mart, Grarup, Niels, Schmidt, Ellen M, Pan, Ian, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloe, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Ahmad, Meraj, Noordam, Raymond, Lim, Victor JY, Tam, Claudia HT, Joo, Yoonjung Yoonie, Chen, Chien-Hsiun, Raffield, Laura M, Lecoeur, Cécile, Prins, Bram Peter, Nicolas, Aude, Yanek, Lisa R, Chen, Guanjie, Jensen, Richard A, Tajuddin, Salman, Kabagambe, Edmond K, An, Ping, Xiang, Anny H, Choi, Hyeok Sun, Cade, Brian E, Tan, Jingyi, Flanagan, Jack, Abaitua, Fernando, Adair, Linda S, Adeyemo, Adebowale, Aguilar-Salinas, Carlos A, Akiyama, Masato, Anand, Sonia S, Bertoni, Alain, Bian, Zheng, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A, Brummett, Chad M, Buchanan, Thomas A, Canouil, Mickaël, Chan, Juliana CN, Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, and Cushman, Mary

Subjects
Genetics, Diabetes, Human Genome, Metabolic and endocrine, Diabetes Mellitus, Type 2, Ethnicity, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors, FinnGen, eMERGE Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P 50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.

Published
2022

7. An atlas of genetic scores to predict multi-omic traits

Author

Xu, Yu, Ritchie, Scott C., Liang, Yujian, Timmers, Paul R. H. J., Pietzner, Maik, Lannelongue, Loïc, Lambert, Samuel A., Tahir, Usman A., May-Wilson, Sebastian, Foguet, Carles, Johansson, Åsa, Surendran, Praveen, Nath, Artika P., Persyn, Elodie, Peters, James E., Oliver-Williams, Clare, Deng, Shuliang, Prins, Bram, Luan, Jian’an, Bomba, Lorenzo, Soranzo, Nicole, Di Angelantonio, Emanuele, Pirastu, Nicola, Tai, E. Shyong, van Dam, Rob M., Parkinson, Helen, Davenport, Emma E., Paul, Dirk S., Yau, Christopher, Gerszten, Robert E., Mälarstig, Anders, Danesh, John, Sim, Xueling, Langenberg, Claudia, Wilson, James F., Butterworth, Adam S., and Inouye, Michael

Published
2023
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8. 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 JL, 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 PJ, 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 WV, 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, and Loeffler, Markus

Subjects
Animals, Humans, Drosophila melanogaster, Albuminuria, Diabetes Mellitus, Genetic Predisposition to Disease, Creatinine, Risk Factors, Chromosome Mapping, Gene Expression Regulation, Meta-Analysis as Topic, Genome-Wide Association Study, Genetic Loci, Phenomics
Abstract

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

Published
2019

9. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author

Prins, Bram P, Mead, Timothy J, Brody, Jennifer A, Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A, van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T, Gabriel, George C, Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M, Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching-Ti, Lyytikäinen, Leo-Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V, Verweij, Niek, Warren, Helen R, Weiss, Stefan, Alonso, Alvaro, Arnar, David O, Bots, Michiel L, de Boer, Rudolf A, Dominiczak, Anna F, Eijgelsheim, Mark, Ellinor, Patrick T, Guo, Xiuqing, Felix, Stephan B, Harris, Tamara B, Hayward, Caroline, Heckbert, Susan R, Huang, Paul L, Jukema, JW, Kähönen, Mika, Kors, Jan A, Lambiase, Pier D, Launer, Lenore J, Li, Man, Linneberg, Allan, Nelson, Christopher P, Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M, Raitakari, Olli T, Rice, Kenneth M, Rotter, Jerome I, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Tim D, Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G, Xie, Zhijun, Asselbergs, Folkert W, Dörr, Marcus, van Duijn, Cornelia M, Gasparini, Paolo, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J, Lubitz, Steven A, Mook-Kanamori, Dennis O, Conti, Francesco J, Newton-Cheh, Christopher H, Rosand, Jonathan, Rudan, Igor, and Samani, Nilesh J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Cardiovascular, Human Genome, Heart Disease, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, ADAMTS Proteins, Animals, Black People, Connexin 43, Electrocardiography, Exome, Female, Gene Expression, Gene Expression Profiling, Genetic Loci, Genome-Wide Association Study, Heart Conduction System, Humans, Male, Mice, Middle Aged, Myocardium, Open Reading Frames, Polymorphism, Single Nucleotide, White People, Exome Sequencing, Exome chip, Conduction, ADAMTS6, Meta-analysis, Environmental Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundGenome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.ResultsHere, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction.ConclusionsOur approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.

Published
2018

10. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

Author

Ligthart, Symen, Vaez, Ahmad, Võsa, Urmo, Stathopoulou, Maria G, de Vries, Paul S, Prins, Bram P, Van der Most, Peter J, Tanaka, Toshiko, Naderi, Elnaz, Rose, Lynda M, Wu, Ying, Karlsson, Robert, Barbalic, Maja, Lin, Honghuang, Pool, René, Zhu, Gu, Macé, Aurélien, Sidore, Carlo, Trompet, Stella, Mangino, Massimo, Sabater-Lleal, Maria, Kemp, John P, Abbasi, Ali, Kacprowski, Tim, Verweij, Niek, Smith, Albert V, Huang, Tao, Marzi, Carola, Feitosa, Mary F, Lohman, Kurt K, Kleber, Marcus E, Milaneschi, Yuri, Mueller, Christian, Huq, Mahmudul, Vlachopoulou, Efthymia, Lyytikäinen, Leo-Pekka, Oldmeadow, Christopher, Deelen, Joris, Perola, Markus, Zhao, Jing Hua, Feenstra, Bjarke, Amini, Marzyeh, Lahti, Jari, Schraut, Katharina E, Fornage, Myriam, Suktitipat, Bhoom, Chen, Wei-Min, Li, Xiaohui, Nutile, Teresa, Malerba, Giovanni, Luan, Jian’an, Bak, Tom, Schork, Nicholas, Del Greco M., Fabiola, Thiering, Elisabeth, Mahajan, Anubha, Marioni, Riccardo E, Mihailov, Evelin, Eriksson, Johan, Ozel, Ayse Bilge, Zhang, Weihua, Nethander, Maria, Cheng, Yu-Ching, Aslibekyan, Stella, Ang, Wei, Gandin, Ilaria, Yengo, Loïc, Portas, Laura, Kooperberg, Charles, Hofer, Edith, Rajan, Kumar B, Schurmann, Claudia, Hollander, Wouter den, Ahluwalia, Tarunveer Singh, Zhao, Jing, Draisma, Harmen HM, Ford, Ian, Timpson, Nicholas, Teumer, Alexander, Huang, Hongyan, Wahl, Simone, Liu, YongMei, Huang, Jie, Uh, Hae-Won, Geller, Frank, Joshi, Peter K, Yanek, Lisa R, Trabetti, Elisabetta, Lehne, Benjamin, Vozzi, Diego, Verbanck, Marie, Biino, Ginevra, Saba, Yasaman, Meulenbelt, Ingrid, O’Connell, Jeff R, Laakso, Markku, Giulianini, Franco, Magnusson, Patrik KE, Ballantyne, Christie M, and Hottenga, Jouke Jan

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Mental Illness, Prevention, Mental Health, 2.1 Biological and endogenous factors, Inflammatory and immune system, Generic health relevance, Mental health, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Bipolar Disorder, Body Mass Index, C-Reactive Protein, Child, Female, Genetic Loci, Genome-Wide Association Study, Humans, Inflammation, Liver, Male, Mendelian Randomization Analysis, Metabolic Networks and Pathways, Middle Aged, Schizophrenia, Young Adult, LifeLines Cohort Study, CHARGE Inflammation Working Group, C-reactive protein, DEPICT, Mendelian randomization, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, schizophrenia, system biology, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

Published
2018

11. Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

Author

Mahajan, Anubha, Wessel, Jennifer, Willems, Sara M, Zhao, Wei, Robertson, Neil R, Chu, Audrey Y, Gan, Wei, Kitajima, Hidetoshi, Taliun, Daniel, Rayner, N William, Guo, Xiuqing, Lu, Yingchang, Li, Man, Jensen, Richard A, Hu, Yao, Huo, Shaofeng, Lohman, Kurt K, Zhang, Weihua, Cook, James P, Prins, Bram Peter, Flannick, Jason, Grarup, Niels, Trubetskoy, Vassily Vladimirovich, Kravic, Jasmina, Kim, Young Jin, Rybin, Denis V, Yaghootkar, Hanieh, Müller-Nurasyid, Martina, Meidtner, Karina, Li-Gao, Ruifang, Varga, Tibor V, Marten, Jonathan, Li, Jin, Smith, Albert Vernon, An, Ping, Ligthart, Symen, Gustafsson, Stefan, Malerba, Giovanni, Demirkan, Ayse, Tajes, Juan Fernandez, Steinthorsdottir, Valgerdur, Wuttke, Matthias, Lecoeur, Cécile, Preuss, Michael, Bielak, Lawrence F, Graff, Marielisa, Highland, Heather M, Justice, Anne E, Liu, Dajiang J, Marouli, Eirini, Peloso, Gina Marie, Warren, Helen R, ExomeBP Consortium, MAGIC Consortium, GIANT Consortium, Afaq, Saima, Afzal, Shoaib, Ahlqvist, Emma, Almgren, Peter, Amin, Najaf, Bang, Lia B, Bertoni, Alain G, Bombieri, Cristina, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A, Burtt, Noël P, Canouil, Mickaël, Chen, Yii-Der Ida, Cho, Yoon Shin, Christensen, Cramer, Eastwood, Sophie V, Eckardt, Kai-Uwe, Fischer, Krista, Gambaro, Giovanni, Giedraitis, Vilmantas, Grove, Megan L, de Haan, Hugoline G, Hackinger, Sophie, Hai, Yang, Han, Sohee, Tybjærg-Hansen, Anne, Hivert, Marie-France, Isomaa, Bo, Jäger, Susanne, Jørgensen, Marit E, Jørgensen, Torben, Käräjämäki, Annemari, Kim, Bong-Jo, Kim, Sung Soo, Koistinen, Heikki A, Kovacs, Peter, Kriebel, Jennifer, Kronenberg, Florian, Läll, Kristi, Lange, Leslie A, Lee, Jung-Jin, Lehne, Benjamin, Li, Huaixing, and Lin, Keng-Hung

Subjects
ExomeBP Consortium, MAGIC Consortium, GIANT Consortium, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Chromosome Mapping, Alleles, European Continental Ancestry Group, Female, Male, Genetic Variation, Genome-Wide Association Study, Whole Exome Sequencing, Diabetes Mellitus, Type 2, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P

Published
2018

12. Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke

Author

Chen, Lingyan, Peters, James E., Prins, Bram, Persyn, Elodie, Traylor, Matthew, Surendran, Praveen, Karthikeyan, Savita, Yonova-Doing, Ekaterina, Di Angelantonio, Emanuele, Roberts, David J., Watkins, Nicholas A., Ouwehand, Willem H., Danesh, John, Lewis, Cathryn M., Bronson, Paola G., Markus, Hugh S., Burgess, Stephen, Butterworth, Adam S., and Howson, Joanna M. M.

Published
2022
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13. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals

Author

Bihlmeyer, Nathan A, Brody, Jennifer A, Smith, Albert Vernon, Warren, Helen R, Lin, Honghuang, Isaacs, Aaron, Liu, Ching-Ti, Marten, Jonathan, Radmanesh, Farid, Hall, Leanne M, Grarup, Niels, Mei, Hao, Müller-Nurasyid, Martina, Huffman, Jennifer E, Verweij, Niek, Guo, Xiuqing, Yao, Jie, Li-Gao, Ruifang, van den Berg, Marten, Weiss, Stefan, Prins, Bram P, van Setten, Jessica, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Bis, Joshua C, Austin, Tom, Chen, Yii-Der Ida, Psaty, Bruce M, Harrris, Tamara B, Launer, Lenore J, Padmanabhan, Sandosh, Dominiczak, Anna, Huang, Paul L, Xie, Zhijun, Ellinor, Patrick T, Kors, Jan A, Campbell, Archie, Murray, Alison D, Nelson, Christopher P, Tobin, Martin D, Bork-Jensen, Jette, Hansen, Torben, Pedersen, Oluf, Linneberg, Allan, Sinner, Moritz F, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Perz, Siegfried, Kolcic, Ivana, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Lin, Henry J, Taylor, Kent D, de Mutsert, Renée, Trompet, Stella, Jukema, J Wouter, Maan, Arie C, Stricker, Bruno HC, Rivadeneira, Fernando, Uitterlinden, André, Völker, Uwe, Homuth, Georg, Völzke, Henry, Felix, Stephan B, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Raitakari, Olli T, Kähönen, Mika, Mononen, Nina, Gudnason, Vilmundur, Munroe, Patricia B, Lubitz, Steven A, van Duijn, Cornelia M, Newton-Cheh, Christopher H, Hayward, Caroline, Rosand, Jonathan, Samani, Nilesh J, Kanters, Jørgen K, Wilson, James G, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Rotter, Jerome I, Mook-Kanamori, Dennis O, Eijgelsheim, Mark, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Arking, Dan E, and Sotoodehnia, Nona

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Genetics, Prevention, Heart Disease, Cardiovascular, 1.1 Normal biological development and functioning, Antiporters, DNA-Binding Proteins, Electrocardiography, Exome, Genome-Wide Association Study, Humans, Long QT Syndrome, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Receptors, Calcium-Sensing, Transcription Factors, arrhythmias, cardiac, death, sudden, cardiac, genetics, genome, humans, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundQT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest.Methods and resultsWe performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci.ConclusionsOur analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.

Published
2018

14. Discovery of novel heart rate-associated loci using the Exome Chip

Author

van den Berg, Marten E, Warren, Helen R, Cabrera, Claudia P, Verweij, Niek, Mifsud, Borbala, Haessler, Jeffrey, Bihlmeyer, Nathan A, Fu, Yi-Ping, Weiss, Stefan, Lin, Henry J, Grarup, Niels, Li-Gao, Ruifang, Pistis, Giorgio, Shah, Nabi, Brody, Jennifer A, Müller-Nurasyid, Martina, Lin, Honghuang, Mei, Hao, Smith, Albert V, Lyytikäinen, Leo-Pekka, Hall, Leanne M, van Setten, Jessica, Trompet, Stella, Prins, Bram P, Isaacs, Aaron, Radmanesh, Farid, Marten, Jonathan, Entwistle, Aiman, Kors, Jan A, Silva, Claudia T, Alonso, Alvaro, Bis, Joshua C, de Boer, Rudolf, de Haan, Hugoline G, de Mutsert, Renée, Dedoussis, George, Dominiczak, Anna F, Doney, Alex SF, Ellinor, Patrick T, Eppinga, Ruben N, Felix, Stephan B, Guo, Xiuqing, Hagemeijer, Yanick, Hansen, Torben, Harris, Tamara B, Heckbert, Susan R, Huang, Paul L, Hwang, Shih-Jen, Kähönen, Mika, Kanters, Jørgen K, Kolcic, Ivana, Launer, Lenore J, Li, Man, Yao, Jie, Linneberg, Allan, Liu, Simin, Macfarlane, Peter W, Mangino, Massimo, Morris, Andrew D, Mulas, Antonella, Murray, Alison D, Nelson, Christopher P, Orrú, Marco, Padmanabhan, Sandosh, Peters, Annette, Porteous, David J, Poulter, Neil, Psaty, Bruce M, Qi, Lihong, Raitakari, Olli T, Rivadeneira, Fernando, Roselli, Carolina, Rudan, Igor, Sattar, Naveed, Sever, Peter, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Timothy D, Stanton, Alice V, Stirrups, Kathleen E, Taylor, Kent D, Tobin, Martin D, Uitterlinden, André, Vaartjes, Ilonca, Hoes, Arno W, van der Meer, Peter, Völker, Uwe, Waldenberger, Melanie, Xie, Zhijun, Zoledziewska, Magdalena, Tinker, Andrew, Polasek, Ozren, Rosand, Jonathan, Jamshidi, Yalda, van Duijn, Cornelia M, Zeggini, Eleftheria, Jukema, J Wouter, Asselbergs, Folkert W, Samani, Nilesh J, and Lehtimäki, Terho

Subjects
Biological Sciences, Genetics, Stem Cell Research, Cardiovascular, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Adult, Alleles, Exome, Female, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Heart Rate, Humans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Risk Factors, White People, Medical and Health Sciences, Genetics & Heredity
Abstract

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.

Published
2017

15. Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19

Author

Gaziano, Liam, Giambartolomei, Claudia, Pereira, Alexandre C., Gaulton, Anna, Posner, Daniel C., Swanson, Sonja A., Ho, Yuk-Lam, Iyengar, Sudha K., Kosik, Nicole M., Vujkovic, Marijana, Gagnon, David R., Bento, A. Patrícia, Barrio-Hernandez, Inigo, Rönnblom, Lars, Hagberg, Niklas, Lundtoft, Christian, Langenberg, Claudia, Pietzner, Maik, Valentine, Dennis, Gustincich, Stefano, Tartaglia, Gian Gaetano, Allara, Elias, Surendran, Praveen, Burgess, Stephen, Zhao, Jing Hua, Peters, James E., Prins, Bram P., Angelantonio, Emanuele Di, Devineni, Poornima, Shi, Yunling, Lynch, Kristine E., DuVall, Scott L., Garcon, Helene, Thomann, Lauren O., Zhou, Jin J., Gorman, Bryan R., Huffman, Jennifer E., O’Donnell, Christopher J., Tsao, Philip S., Beckham, Jean C., Pyarajan, Saiju, Muralidhar, Sumitra, Huang, Grant D., Ramoni, Rachel, Beltrao, Pedro, Danesh, John, Hung, Adriana M., Chang, Kyong-Mi, Sun, Yan V., Joseph, Jacob, Leach, Andrew R., Edwards, Todd L., Cho, Kelly, Gaziano, J. Michael, Butterworth, Adam S., and Casas, Juan P.

Published
2021
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16. 52 Genetic Loci Influencing Myocardial Mass

Author

van der Harst, Pim, van Setten, Jessica, Verweij, Niek, Vogler, Georg, Franke, Lude, Maurano, Matthew T, Wang, Xinchen, Leach, Irene Mateo, Eijgelsheim, Mark, Sotoodehnia, Nona, Hayward, Caroline, Sorice, Rossella, Meirelles, Osorio, Lyytikäinen, Leo-Pekka, Polašek, Ozren, Tanaka, Toshiko, Arking, Dan E, Ulivi, Sheila, Trompet, Stella, Müller-Nurasyid, Martina, Smith, Albert V, Dörr, Marcus, Kerr, Kathleen F, Magnani, Jared W, Del Greco M., Fabiola, Zhang, Weihua, Nolte, Ilja M, Silva, Claudia T, Padmanabhan, Sandosh, Tragante, Vinicius, Esko, Tõnu, Abecasis, Gonçalo R, Adriaens, Michiel E, Andersen, Karl, Barnett, Phil, Bis, Joshua C, Bodmer, Rolf, Buckley, Brendan M, Campbell, Harry, Cannon, Megan V, Chakravarti, Aravinda, Chen, Lin Y, Delitala, Alessandro, Devereux, Richard B, Doevendans, Pieter A, Dominiczak, Anna F, Ferrucci, Luigi, Ford, Ian, Gieger, Christian, Harris, Tamara B, Haugen, Eric, Heinig, Matthias, Hernandez, Dena G, Hillege, Hans L, Hirschhorn, Joel N, Hofman, Albert, Hubner, Norbert, Hwang, Shih-Jen, Iorio, Annamaria, Kähönen, Mika, Kellis, Manolis, Kolcic, Ivana, Kooner, Ishminder K, Kooner, Jaspal S, Kors, Jan A, Lakatta, Edward G, Lage, Kasper, Launer, Lenore J, Levy, Daniel, Lundby, Alicia, Macfarlane, Peter W, May, Dalit, Meitinger, Thomas, Metspalu, Andres, Nappo, Stefania, Naitza, Silvia, Neph, Shane, Nord, Alex S, Nutile, Teresa, Okin, Peter M, Olsen, Jesper V, Oostra, Ben A, Penninger, Josef M, Pennacchio, Len A, Pers, Tune H, Perz, Siegfried, Peters, Annette, Pinto, Yigal M, Pfeufer, Arne, Pilia, Maria Grazia, Pramstaller, Peter P, Prins, Bram P, Raitakari, Olli T, Raychaudhuri, Soumya, Rice, Ken M, Rossin, Elizabeth J, Rotter, Jerome I, Schafer, Sebastian, Schlessinger, David, and Schmidt, Carsten O

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Heart Disease - Coronary Heart Disease, Human Genome, Heart Disease, Biotechnology, Cardiovascular, Genetics, 2.1 Biological and endogenous factors, Animals, Cardiomegaly, Genetic Loci, Genome-Wide Association Study, Humans, electrocardiogram, genetic association study, heart failure, left ventricular hypertrophy, QRS, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundMyocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.ObjectivesThis meta-analysis sought to gain insights into the genetic determinants of myocardial mass.MethodsWe carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.ResultsWe identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.ConclusionsTaken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.

Published
2016

17. Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals

Author

Folkersen, Lasse, Gustafsson, Stefan, Wang, Qin, Hansen, Daniel Hvidberg, Hedman, Åsa K., Schork, Andrew, Page, Karen, Zhernakova, Daria V., Wu, Yang, Peters, James, Eriksson, Niclas, Bergen, Sarah E., Boutin, Thibaud S., Bretherick, Andrew D., Enroth, Stefan, Kalnapenkis, Anette, Gådin, Jesper R., Suur, Bianca E., Chen, Yan, Matic, Ljubica, Gale, Jeremy D., Lee, Julie, Zhang, Weidong, Quazi, Amira, Ala-Korpela, Mika, Choi, Seung Hoan, Claringbould, Annique, Danesh, John, Davey Smith, George, de Masi, Federico, Elmståhl, Sölve, Engström, Gunnar, Fauman, Eric, Fernandez, Celine, Franke, Lude, Franks, Paul W., Giedraitis, Vilmantas, Haley, Chris, Hamsten, Anders, Ingason, Andres, Johansson, Åsa, Joshi, Peter K., Lind, Lars, Lindgren, Cecilia M., Lubitz, Steven, Palmer, Tom, Macdonald-Dunlop, Erin, Magnusson, Martin, Melander, Olle, Michaelsson, Karl, Morris, Andrew P., Mägi, Reedik, Nagle, Michael W., Nilsson, Peter M., Nilsson, Jan, Orho-Melander, Marju, Polasek, Ozren, Prins, Bram, Pålsson, Erik, Qi, Ting, Sjögren, Marketa, Sundström, Johan, Surendran, Praveen, Võsa, Urmo, Werge, Thomas, Wernersson, Rasmus, Westra, Harm-Jan, Yang, Jian, Zhernakova, Alexandra, Ärnlöv, Johan, Fu, Jingyuan, Smith, J. Gustav, Esko, Tõnu, Hayward, Caroline, Gyllensten, Ulf, Landen, Mikael, Siegbahn, Agneta, Wilson, James F., Wallentin, Lars, Butterworth, Adam S., Holmes, Michael V., Ingelsson, Erik, and Mälarstig, Anders

Published
2020
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18. Sequencing of SCN5A Identifies Rare and Common Variants Associated With Cardiac Conduction

Author

Magnani, Jared W, Brody, Jennifer A, Prins, Bram P, Arking, Dan E, Lin, Honghuang, Yin, Xiaoyan, Liu, Ching-Ti, Morrison, Alanna C, Zhang, Feng, Spector, Tim D, Alonso, Alvaro, Bis, Joshua C, Heckbert, Susan R, Lumley, Thomas, Sitlani, Colleen M, Cupples, L Adrienne, Lubitz, Steven A, Soliman, Elsayed Z, Pulit, Sara L, Newton-Cheh, Christopher, O'Donnell, Christopher J, Ellinor, Patrick T, Benjamin, Emelia J, Muzny, Donna M, Gibbs, Richard A, Santibanez, Jireh, Taylor, Herman A, Rotter, Jerome I, Lange, Leslie A, Psaty, Bruce M, Jackson, Rebecca, Rich, Stephen S, Boerwinkle, Eric, Jamshidi, Yalda, and Sotoodehnia, Nona

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Cardiovascular, Genetics, Health Disparities, Aging, Minority Health, Human Genome, Heart Disease, Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Genetic Variation, Genome-Wide Association Study, Genomics, Heart Conduction System, Heart Diseases, Humans, Male, Middle Aged, NAV1.5 Voltage-Gated Sodium Channel, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, electrocardiography, genomics, CHARGE Consortium, NHLBI Exome Sequencing Project, UK10K, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundThe cardiac sodium channel SCN5A regulates atrioventricular and ventricular conduction. Genetic variants in this gene are associated with PR and QRS intervals. We sought to characterize further the contribution of rare and common coding variation in SCN5A to cardiac conduction.Methods and resultsIn Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study, we performed targeted exonic sequencing of SCN5A (n=3699, European ancestry individuals) and identified 4 common (minor allele frequency >1%) and 157 rare variants. Common and rare SCN5A coding variants were examined for association with PR and QRS intervals through meta-analysis of European ancestry participants from CHARGE, National Heart, Lung, and Blood Institute's Exome Sequencing Project (n=607), and the UK10K (n=1275) and by examining Exome Sequencing Project African ancestry participants (n=972). Rare coding SCN5A variants in aggregate were associated with PR interval in European and African ancestry participants (P=1.3×10(-3)). Three common variants were associated with PR and QRS interval duration among European ancestry participants and one among African ancestry participants. These included 2 well-known missense variants: rs1805124 (H558R) was associated with PR and QRS shortening in European ancestry participants (P=6.25×10(-4) and P=5.2×10(-3), respectively) and rs7626962 (S1102Y) was associated with PR shortening in those of African ancestry (P=2.82×10(-3)). Among European ancestry participants, 2 novel synonymous variants, rs1805126 and rs6599230, were associated with cardiac conduction. Our top signal, rs1805126 was associated with PR and QRS lengthening (P=3.35×10(-7) and P=2.69×10(-4), respectively) and rs6599230 was associated with PR shortening (P=2.67×10(-5)).ConclusionsBy sequencing SCN5A, we identified novel common and rare coding variants associated with cardiac conduction.

Published
2014

19. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

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, Benjamin, Emelia, Chasman, Daniel I., Dehghan, Abbas, Ahluwalia, Tarunveer Singh, Meigs, James, Tracy, Russell, Ligthart, Symen, Bis, Josh, Eiriksdottir, Gudny, Pankratz, Nathan, Gross, Myron, Rainer, Alex, Wilson, James G., Psaty, Bruce M., Dupuis, Josee, Prins, Bram, Vaso, Urmo, Stathopoulou, Maria, Lehtimaki, Terho, Koenig, Wolfgang, Jamshidi, Yalda, Siest, Sophie, Abbasi, Ali, Uitterlinden, Andre G., Abdollahi, Mohammadreza, Schnabel, Renate, Schick, Ursula M., Nolte, Ilja M., Kraja, Aldi, Hsu, Yi-Hsiang, Tylee, Daniel S., Zwicker, Alyson, Uher, Rudolf, Davey-Smith, George, Morrison, Alanna C., Hicks, Andrew, van Duijn, Cornelia M., Ward-Caviness, Cavin, Boerwinkle, Eric, Rotter, J., Rice, Ken, Lange, Leslie, Perola, Markus, de Geus, Eco, Morris, Andrew P., Makela, Kari Matti, Stacey, David, Eriksson, Johan, Frayling, Tim M., Slagboom, Eline P., Vaez, Ahmad, Võsa, Urmo, Stathopoulou, Maria G., de Vries, Paul S., Prins, Bram P., Van der Most, Peter J., Tanaka, Toshiko, Naderi, Elnaz, Rose, Lynda M., Wu, Ying, Karlsson, Robert, Barbalic, Maja, Lin, Honghuang, Pool, René, Zhu, Gu, Macé, Aurélien, Sidore, Carlo, Trompet, Stella, Mangino, Massimo, Sabater-Lleal, Maria, Kemp, John P., Kacprowski, Tim, Verweij, Niek, Smith, Albert V., Huang, Tao, Marzi, Carola, Feitosa, Mary F., Lohman, Kurt K., Kleber, Marcus E., Milaneschi, Yuri, Mueller, Christian, Huq, Mahmudul, Vlachopoulou, Efthymia, Lyytikäinen, Leo-Pekka, Oldmeadow, Christopher, Deelen, Joris, Zhao, Jing Hua, Feenstra, Bjarke, Amini, Marzyeh, Lahti, Jari, Schraut, Katharina E., Fornage, Myriam, Suktitipat, Bhoom, Chen, Wei-Min, Li, Xiaohui, Nutile, Teresa, Malerba, Giovanni, Luan, Jian’an, Bak, Tom, Schork, Nicholas, Del Greco M., Fabiola, Thiering, Elisabeth, Mahajan, Anubha, Marioni, Riccardo E., Mihailov, Evelin, Eriksson, Joel, Ozel, Ayse Bilge, Zhang, Weihua, Nethander, Maria, Cheng, Yu-Ching, Aslibekyan, Stella, Ang, Wei, Gandin, Ilaria, Yengo, Loïc, Portas, Laura, Kooperberg, Charles, Hofer, Edith, Rajan, Kumar B., Schurmann, Claudia, den Hollander, Wouter, Ahluwalia, Tarunveer S., Zhao, Jing, Draisma, Harmen H.M., Ford, Ian, Timpson, Nicholas, Teumer, Alexander, Huang, Hongyan, Wahl, Simone, Liu, YongMei, Huang, Jie, Uh, Hae-Won, Geller, Frank, Joshi, Peter K., Yanek, Lisa R., Trabetti, Elisabetta, Lehne, Benjamin, Vozzi, Diego, Verbanck, Marie, Biino, Ginevra, Saba, Yasaman, Meulenbelt, Ingrid, O’Connell, Jeff R., Laakso, Markku, Giulianini, Franco, Magnusson, Patrik K.E., Ballantyne, Christie M., Hottenga, Jouke Jan, Montgomery, Grant W., Rivadineira, Fernando, Rueedi, Rico, Steri, Maristella, Herzig, Karl-Heinz, Stott, David J., Menni, Cristina, Frånberg, Mattias, St. Pourcain, Beate, Felix, Stephan B., Pers, Tune H., Bakker, Stephan J.L., Kraft, Peter, Peters, Annette, Vaidya, Dhananjay, Delgado, Graciela, Smit, Johannes H., Großmann, Vera, Sinisalo, Juha, Seppälä, Ilkka, Williams, Stephen R., Holliday, Elizabeth G., Moed, Matthijs, Langenberg, Claudia, Räikkönen, Katri, Ding, Jingzhong, Campbell, Harry, Sale, Michele M., Chen, Yii-Der I., James, Alan L., Ruggiero, Daniela, Soranzo, Nicole, Hartman, Catharina A., Smith, Erin N., Berenson, Gerald S., Fuchsberger, Christian, Hernandez, Dena, Tiesler, Carla M.T., Giedraitis, Vilmantas, Liewald, David, Fischer, Krista, Mellström, Dan, Larsson, Anders, Wang, Yunmei, Scott, William R., Lorentzon, Matthias, Beilby, John, Ryan, Kathleen A., Pennell, Craig E., Vuckovic, Dragana, Balkau, Beverly, Concas, Maria Pina, Schmidt, Reinhold, Mendes de Leon, Carlos F., Bottinger, Erwin P., Kloppenburg, Margreet, Paternoster, Lavinia, Boehnke, Michael, Musk, A.W., Willemsen, Gonneke, Evans, David M., Madden, Pamela A.F., Kähönen, Mika, Kutalik, Zoltán, Zoledziewska, Magdalena, Karhunen, Ville, Kritchevsky, Stephen B., Sattar, Naveed, Lachance, Genevieve, Clarke, Robert, Harris, Tamara B., Raitakari, Olli T., Attia, John R., van Heemst, Diana, Kajantie, Eero, Sorice, Rossella, Gambaro, Giovanni, Scott, Robert A., Hicks, Andrew A., Ferrucci, Luigi, Standl, Marie, Lindgren, Cecilia M., Starr, John M., Karlsson, Magnus, Lind, Lars, Li, Jun Z., Chambers, John C., Mori, Trevor A., de Geus, Eco J.C.N., Heath, Andrew C., Martin, Nicholas G., Auvinen, Juha, Buckley, Brendan M., de Craen, Anton J.M., Waldenberger, Melanie, Strauch, Konstantin, Meitinger, Thomas, Scott, Rodney J., McEvoy, Mark, Beekman, Marian, Bombieri, Cristina, Ridker, Paul M., Mohlke, Karen L., Pedersen, Nancy L., Boomsma, Dorret I., Whitfield, John B., Strachan, David P., Hofman, Albert, Vollenweider, Peter, Cucca, Francesco, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Spector, Tim D., Hamsten, Anders, Zeller, Tanja, Uitterlinden, André G., Nauck, Matthias, Gudnason, Vilmundur, Qi, Lu, Grallert, Harald, Borecki, Ingrid B., Rotter, Jerome I., März, Winfried, Wild, Philipp S., Lokki, Marja-Liisa, Boyle, Michael, Salomaa, Veikko, Melbye, Mads, Eriksson, Johan G., Wilson, James F., Penninx, Brenda W.J.H., Becker, Diane M., Worrall, Bradford B., Gibson, Greg, Krauss, Ronald M., Ciullo, Marina, Zaza, Gianluigi, Wareham, Nicholas J., Oldehinkel, Albertine J., Palmer, Lyle J., Murray, Sarah S., Pramstaller, Peter P., Bandinelli, Stefania, Heinrich, Joachim, Ingelsson, Erik, Deary, Ian J., Mägi, Reedik, Vandenput, Liesbeth, Desch, Karl C., Kooner, Jaspal S., Ohlsson, Claes, Hayward, Caroline, Lehtimäki, Terho, Shuldiner, Alan R., Arnett, Donna K., Beilin, Lawrence J., Robino, Antonietta, Froguel, Philippe, Pirastu, Mario, Jess, Tine, Loos, Ruth J.F., Evans, Denis A., Schmidt, Helena, Smith, George Davey, Slagboom, P. Eline, Tracy, Russell P., Visvikis-Siest, Sophie, Reiner, Alex P., Bis, Joshua C., Franco, Oscar H., Benjamin, Emelia J., and Dupuis, Josée

Published
2018
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20. Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits

Author

van Setten, Jessica, Verweij, Niek, Mbarek, Hamdi, Niemeijer, Maartje N., Trompet, Stella, Arking, Dan E., Brody, Jennifer A., Gandin, Ilaria, Grarup, Niels, Hall, Leanne M., Hemerich, Daiane, Lyytikäinen, Leo-Pekka, Mei, Hao, Müller-Nurasyid, Martina, Prins, Bram P., Robino, Antonietta, Smith, Albert V., Warren, Helen R., Asselbergs, Folkert W., Boomsma, Dorret I., Caulfield, Mark J., Eijgelsheim, Mark, Ford, Ian, Hansen, Torben, Harris, Tamara B., Heckbert, Susan R., Hottenga, Jouke-Jan, Iorio, Annamaria, Kors, Jan A., Linneberg, Allan, MacFarlane, Peter W., Meitinger, Thomas, Nelson, Christopher P., Raitakari, Olli T., Silva Aldana, Claudia T., Sinagra, Gianfranco, Sinner, Moritz, Soliman, Elsayed Z., Stoll, Monika, Uitterlinden, Andre, van Duijn, Cornelia M., Waldenberger, Melanie, Alonso, Alvaro, Gasparini, Paolo, Gudnason, Vilmundur, Jamshidi, Yalda, Kääb, Stefan, Kanters, Jørgen K., Lehtimäki, Terho, Munroe, Patricia B., Peters, Annette, Samani, Nilesh J., Sotoodehnia, Nona, Ulivi, Sheila, Wilson, James G., de Geus, Eco J. C., Jukema, J. Wouter, Stricker, Bruno, van der Harst, Pim, de Bakker, Paul I. W., and Isaacs, Aaron

Published
2019
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21. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

Author

Mahajan, Anubha, Taliun, Daniel, Thurner, Matthias, Robertson, Neil R., Torres, Jason M., Rayner, N. William, Payne, Anthony J., Steinthorsdottir, Valgerdur, Scott, Robert A., Grarup, Niels, Cook, James P., Schmidt, Ellen M., Wuttke, Matthias, Sarnowski, Chloé, Mägi, Reedik, Nano, Jana, Gieger, Christian, Trompet, Stella, Lecoeur, Cécile, Preuss, Michael H., Prins, Bram Peter, Guo, Xiuqing, Bielak, Lawrence F., Below, Jennifer E., Bowden, Donald W., Chambers, John Campbell, Kim, Young Jin, Ng, Maggie C. Y., Petty, Lauren E., Sim, Xueling, Zhang, Weihua, Bennett, Amanda J., Bork-Jensen, Jette, Brummett, Chad M., Canouil, Mickaël, Ec kardt, Kai-Uwe, Fischer, Krista, Kardia, Sharon L. R., Kronenberg, Florian, Läll, Kristi, Liu, Ching-Ti, Locke, Adam E., Luan, Jian’an, Ntalla, Ioanna, Nylander, Vibe, Schönherr, Sebastian, Schurmann, Claudia, Yengo, Loïc, Bottinger, Erwin P., Brandslund, Ivan, Christensen, Cramer, Dedoussis, George, Florez, Jose C., Ford, Ian, Franco, Oscar H., Frayling, Timothy M., Giedraitis, Vilmantas, Hackinger, Sophie, Hattersley, Andrew T., Herder, Christian, Ikram, M. Arfan, Ingelsson, Martin, Jørgensen, Marit E., Jørgensen, Torben, Kriebel, Jennifer, Kuusisto, Johanna, Ligthart, Symen, Lindgren, Cecilia M., Linneberg, Allan, Lyssenko, Valeriya, Mamakou, Vasiliki, Meitinger, Thomas, Mohlke, Karen L., Morris, Andrew D., Nadkarni, Girish, Pankow, James S., Peters, Annette, Sattar, Naveed, Stančáková, Alena, Strauch, Konstantin, Taylor, Kent D., Thorand, Barbara, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tuomilehto, Jaakko, Witte, Daniel R., Dupuis, Josée, Peyser, Patricia A., Zeggini, Eleftheria, Loos, Ruth J. F., Froguel, Philippe, Ingelsson, Erik, Lind, Lars, Groop, Leif, Laakso, Markku, Collins, Francis S., Jukema, J. Wouter, Palmer, Colin N. A., Grallert, Harald, Metspalu, Andres, Dehghan, Abbas, Köttgen, Anna, Abecasis, Goncalo R., Meigs, James B., Rotter, Jerome I., Marchini, Jonathan, Pedersen, Oluf, Hansen, Torben, Langenberg, Claudia, Wareham, Nicholas J., Stefansson, Kari, Gloyn, Anna L., Morris, Andrew P., Boehnke, Michael, and McCarthy, Mark I.

Published
2018
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22. Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Author

Evangelou, Evangelos, Warren, Helen R., Mosen-Ansorena, David, Mifsud, Borbala, Pazoki, Raha, Gao, He, Ntritsos, Georgios, Dimou, Niki, Cabrera, Claudia P., Karaman, Ibrahim, Ng, Fu Liang, Evangelou, Marina, Witkowska, Katarzyna, Tzanis, Evan, Hellwege, Jacklyn N., Giri, Ayush, Velez Edwards, Digna R., Sun, Yan V., Cho, Kelly, Gaziano, J. Michael, Wilson, Peter W. F., Tsao, Philip S., Kovesdy, Csaba P., Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Debette, Stéphanie, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G., Jackson, Anne U., Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian’an, Mangino, Massimo, Oldmeadow, Christopher, Prins, Bram Peter, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M., Zhao, Jing-Hua, Amouyel, Philippe, Connell, John, de Mutsert, Renée, Doney, Alex S. F., Farrall, Martin, Menni, Cristina, Morris, Andrew D., Noordam, Raymond, Paré, Guillaume, Poulter, Neil R., Shields, Denis C., Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E., Ayers, Kristin L., Barbieri, Caterina M., Batini, Chiara, Bis, Joshua C., Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I., Bottinger, Erwin P., Braund, Peter S., Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C., Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J., Davies, Gail, de Borst, Martin H., de Geus, Eco J., Deary, Ian J., Deelen, Joris, Del Greco M., Fabiola, Demirkale, Cumhur Yusuf, Dörr, Marcus, Ehret, Georg B., Elosua, Roberto, Enroth, Stefan, Erzurumluoglu, A. Mesut, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H., Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J., Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Harris, Sarah E., Hartman, Catharina A., Havulinna, Aki S., Hicks, Andrew A., Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E., Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D., Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D., Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S., Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J., Lehne, Benjamin, Lehtimäki, Terho, Liewald, David C. M., Lin, Li, Lind, Lars, Lindgren, Cecilia M., Liu, YongMei, Loos, Ruth J. F., Lopez, Lorna M., Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P., Morrison, Alanna C., Munson, Peter J., Nalls, Mike A., Nandakumar, Priyanka, Nelson, Christopher P., Niiranen, Teemu, Nolte, Ilja M., Nutile, Teresa, Oldehinkel, Albertine J., Oostra, Ben A., O’Reilly, Paul F., Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, Penninx, Brenda W. J. H., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Nguyen, Quang Tri, Raitakari, Olli T., Ren, Meixia, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M., Ried, Janina S., Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M., Rotter, Jerome I., Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F., Salomaa, Veikko, Samani, Nilesh J., Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V., Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M., Stott, David J., Strachan, David P., Strawbridge, Rona J., Sundström, Johan, Swertz, Morris A., Taylor, Kent D., Teumer, Alexander, Tobin, Martin D., Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G., Vaez, Ahmad, van der Most, Peter J., van Duijn, Cornelia M., Vergnaud, Anne-Claire, Verwoert, Germaine C., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H., Willemsen, Gonneke, Wilson, James F., Wright, Alan F., Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R., Butterworth, Adam S., Chasman, Daniel I., Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna M. M., Laakso, Markku, Lakatta, Edward G., Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O., Palmer, Colin N. A., Risch, Lorenz, Scott, Robert A., Scott, Rodney J., Sever, Peter, Spector, Tim D., van der Harst, Pim, Wareham, Nicholas J., Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B., Newton-Cheh, Christopher, Brown, Morris J., Metspalu, Andres, Hung, Adriana M., O’Donnell, Christopher J., Edwards, Todd L., Psaty, Bruce M., Tzoulaki, Ioanna, Barnes, Michael R., Wain, Louise V., Elliott, Paul, Caulfield, Mark J., and the Million Veteran Program

Published
2018
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23. Genomic atlas of the human plasma proteome

Author

Sun, Benjamin B., Maranville, Joseph C., Peters, James E., Stacey, David, Staley, James R., Blackshaw, James, Burgess, Stephen, Jiang, Tao, Paige, Ellie, Surendran, Praveen, Oliver-Williams, Clare, Kamat, Mihir A., Prins, Bram P., Wilcox, Sheri K., Zimmerman, Erik S., Chi, An, Bansal, Narinder, Spain, Sarah L., Wood, Angela M., Morrell, Nicholas W., Bradley, John R., Janjic, Nebojsa, Roberts, David J., Ouwehand, Willem H., Todd, John A., Soranzo, Nicole, Suhre, Karsten, Paul, Dirk S., Fox, Caroline S., Plenge, Robert M., Danesh, John, Runz, Heiko, and Butterworth, Adam S.

Published
2018
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25. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author

Haworth, Simon, Shapland, Chin Yang, Hayward, Caroline, Prins, Bram P., Felix, Janine F., Medina-Gomez, Carolina, Rivadeneira, Fernando, Wang, Carol, Ahluwalia, Tarunveer S., Vrijheid, Martine, Guxens, Mònica, Sunyer, Jordi, Tachmazidou, Ioanna, Walter, Klaudia, Iotchkova, Valentina, Jackson, Andrew, Cleal, Louise, Huffmann, Jennifer, Min, Josine L., Sass, Lærke, Timmers, Paul R. H. J., UK10K consortium, Davey Smith, George, Fisher, Simon E., Wilson, James F., Cole, Tim J., Fernandez-Orth, Dietmar, Bønnelykke, Klaus, Bisgaard, Hans, Pennell, Craig E., Jaddoe, Vincent W. V., Dedoussis, George, Timpson, Nicholas, Zeggini, Eleftheria, Vitart, Veronique, and St Pourcain, Beate

Published
2019
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26. Genetic mechanisms of 184 neuro-related proteins in human plasma

Author

Repetto, Linda, primary, Chen, Jiantao, additional, Yang, Zhijian, additional, Zhai, Ranran, additional, Timmers, Paul R. H. J., additional, Li, Ting, additional, Twait, Emma L., additional, May-Wilson, Sebastian, additional, Muckian, Marisa D., additional, Prins, Bram P., additional, Png, Grace, additional, Kooperberg, Charles, additional, Johansson, Åsa, additional, Hillary, Robert F., additional, Wheeler, Eleanor, additional, Pan, Lu, additional, He, Yazhou, additional, Klasson, Sofia, additional, Ahmad, Shahzad, additional, Peters, James E., additional, Gilly, Arthur, additional, Karaleftheri, Maria, additional, Tsafantakis, Emmanouil, additional, Haessler, Jeffrey, additional, Gyllensten, Ulf, additional, Harris, Sarah E., additional, Wareham, Nicholas J., additional, Göteson, Andreas, additional, Lagging, Cecilia, additional, Ikram, Mohammad Arfan, additional, van Duijn, Cornelia M., additional, Jern, Christina, additional, Landén, Mikael, additional, Langenberg, Claudia, additional, Deary, Ian J., additional, Marioni, Riccardo E., additional, Enroth, Stefan, additional, Reiner, Alexander P., additional, Dedoussis, George, additional, Zeggini, Eleftheria, additional, Butterworth, Adam S., additional, Mälarstig, Anders, additional, Wilson, James F., additional, Navarro, Pau, additional, and Shen, Xia, additional

Published
2023
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27. Trans-ethnic Genomic Informed Risk Assessment for Alzheimer’s disease: An International Hundred K+ Cohorts Consortium Study

Author

Sleiman, Patrick M., primary, Qu, Hui-Qi, additional, Connolly, John J, additional, Mentch, Frank, additional, Pereira, Alexandre, additional, Lotufo, Paulo A, additional, Tollman, Stephen, additional, Choudhury, Ananyo, additional, Ramsay, Michele, additional, Kato, Norihiro, additional, Ozaki, Kouichi, additional, Mitsumori, Risa, additional, Jeon, Jae-Pil, additional, Hong, Chang Hyung, additional, Son, Sang Joon, additional, Roh, Hyun Woong, additional, Lee, Dong-gi, additional, Mukadam, Naaheed, additional, Foote, Isabelle F, additional, Marshall, Charles R, additional, Butterworth, Adam, additional, Prins, Bram P, additional, Glessner, Joseph T, additional, and Hakonarson, Hakon, additional

Published
2022
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29. Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: the GOMAP study

Author

Mamakou, Vasiliki, Hackinger, Sophie, Zengini, Eleni, Tsompanaki, Evgenia, Marouli, Eirini, Serafetinidis, Ioannis, Prins, Bram, Karabela, Athina, Glezou, Eirini, Southam, Lorraine, Rayner, Nigel W., Kuchenbaecker, Karoline, Lamnissou, Klea, Kontaxakis, Vassilis, Dedoussis, George, Gonidakis, Fragiskos, Thanopoulou, Anastasia, Tentolouris, Nikolaos, and Zeggini, Eleftheria

Published
2018
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30. Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney

Author

Wain, Louise V., Vaez, Ahmad, Jansen, Rick, Joehanes, Roby, van der Most, Peter J., Erzurumluoglu, A. Mesut, O’Reilly, Paul F., Cabrera, Claudia P., Warren, Helen R., Rose, Lynda M., Verwoert, Germaine C., Hottenga, Jouke-Jan, Strawbridge, Rona J., Esko, Tonu, Arking, Dan E., Hwang, Shih-Jen, Guo, Xiuqing, Kutalik, Zoltan, Trompet, Stella, Shrine, Nick, Teumer, Alexander, Ried, Janina S., Bis, Joshua C., Smith, Albert V., Amin, Najaf, Nolte, Ilja M., Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Wareham, Nicholas J., Hofer, Edith, Joshi, Peter K., Kristiansson, Kati, Traglia, Michela, Havulinna, Aki S., Goel, Anuj, Nalls, Mike A., Sõber, Siim, Vuckovic, Dragana, Luan, Jian’an, Del Greco M., Fabiola, Ayers, Kristin L., Marrugat, Jaume, Ruggiero, Daniela, Lopez, Lorna M., Niiranen, Teemu, Enroth, Stefan, Jackson, Anne U., Nelson, Christopher P., Huffman, Jennifer E., Zhang, Weihua, Marten, Jonathan, Gandin, Ilaria, Harris, Sarah E., Zemunik, Tatijana, Lu, Yingchang, Evangelou, Evangelos, Shah, Nabi, de Borst, Martin H., Mangino, Massimo, Prins, Bram P., Campbell, Archie, Li-Gao, Ruifang, Chauhan, Ganesh, Oldmeadow, Christopher, Abecasis, Gonçalo, Abedi, Maryam, Barbieri, Caterina M., Barnes, Michael R., Batini, Chiara, Beilby, John, Blake, Tineka, Boehnke, Michael, Bottinger, Erwin P., Braund, Peter S., Brown, Morris, Brumat, Marco, Campbell, Harry, Chambers, John C., Cocca, Massimiliano, Collins, Francis, Connell, John, Cordell, Heather J., Damman, Jeffrey J., Davies, Gail, de Geus, Eco J., de Mutsert, Renée, Deelen, Joris, Demirkale, Yusuf, Doney, Alex S.F., Dörr, Marcus, Farrall, Martin, Ferreira, Teresa, Frånberg, Mattias, Gao, He, Giedraitis, Vilmantas, Gieger, Christian, Giulianini, Franco, Gow, Alan J., Hamsten, Anders, Harris, Tamara B., Hofman, Albert, Holliday, Elizabeth G., Hui, Jennie, Jarvelin, Marjo-Riitta, Johansson, Åsa, Johnson, Andrew D., Jousilahti, Pekka, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Khaw, Kay-Tee, Kolcic, Ivana, Koskinen, Seppo, Langenberg, Claudia, Larson, Marty, Launer, Lenore J., Lehne, Benjamin, Liewald, David C.M., Lin, Li, Lind, Lars, Mach, François, Mamasoula, Chrysovalanto, Menni, Cristina, Mifsud, Borbala, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew D., Morrison, Alanna C., Munson, Peter J., Nandakumar, Priyanka, Nguyen, Quang Tri, Nutile, Teresa, Oldehinkel, Albertine J., Oostra, Ben A., Org, Elin, Padmanabhan, Sandosh, Palotie, Aarno, Paré, Guillaume, Pattie, Alison, Penninx, Brenda W.J.H., Poulter, Neil, Pramstaller, Peter P., Raitakari, Olli T., Ren, Meixia, Rice, Kenneth, Ridker, Paul M., Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rotter, Jerome I., Rudan, Igor, Saba, Yasaman, Saint Pierre, Aude, Sala, Cinzia F., Sarin, Antti-Pekka, Schmidt, Reinhold, Scott, Rodney, Seelen, Marc A., Shields, Denis C., Siscovick, David, Sorice, Rossella, Stanton, Alice, Stott, David J., Sundström, Johan, Swertz, Morris, Taylor, Kent D., Thom, Simon, Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André G., Völker, Uwe, Vollenweider, Peter, Wild, Sarah, Willemsen, Gonneke, Wright, Alan F., Yao, Jie, Thériault, Sébastien, Conen, David, Attia, John, Sever, Peter, Debette, Stéphanie, Mook-Kanamori, Dennis O., Zeggini, Eleftheria, Spector, Tim D., van der Harst, Pim, Palmer, Colin N.A., Vergnaud, Anne-Claire, Loos, Ruth J.F., Polasek, Ozren, Starr, John M., Girotto, Giorgia, Hayward, Caroline, Kooner, Jaspal S., Lindgren, Cecila M., Vitart, Veronique, Samani, Nilesh J., Tuomilehto, Jaakko, Gyllensten, Ulf, Knekt, Paul, Deary, Ian J., Ciullo, Marina, Elosua, Roberto, Keavney, Bernard D., Hicks, Andrew A., Scott, Robert A., Gasparini, Paolo, Laan, Maris, Liu, YongMei, Watkins, Hugh, Hartman, Catharina A., Salomaa, Veikko, Toniolo, Daniela, Perola, Markus, Wilson, James F., Schmidt, Helena, Zhao, Jing Hua, Lehtimäki, Terho, van Duijn, Cornelia M., Gudnason, Vilmundur, Psaty, Bruce M., Peters, Annette, Rettig, Rainer, James, Alan, Jukema, J. Wouter, Strachan, David P., Palmas, Walter, Metspalu, Andres, Ingelsson, Erik, Boomsma, Dorret I., Franco, Oscar H., Bochud, Murielle, Newton-Cheh, Christopher, Munroe, Patricia B., Elliott, Paul, Chasman, Daniel I., Chakravarti, Aravinda, Knight, Joanne, Morris, Andrew P., Levy, Daniel, Tobin, Martin D., Snieder, Harold, Caulfield, Mark J., and Ehret, Georg B.

Published
2017
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32. Role of common and rare variants in SCN10A: results from the Brugada syndrome QRS locus gene discovery collaborative study

Author

Behr, Elijah R., Savio-Galimberti, Eleonora, Barc, Julien, Holst, Anders G., Petropoulou, Evmorfia, Prins, Bram P., Jabbari, Javad, Torchio, Margherita, Berthet, Myriam, Mizusawa, Yuka, Yang, Tao, Nannenberg, Eline A., Dagradi, Federica, Weeke, Peter, Bastiaenan, Rachel, Ackerman, Michael J., Haunso, Stig, Leenhardt, Antoine, Kääb, Stefan, Probst, Vincent, Redon, Richard, Sharma, Sanjay, Wilde, Arthur, Tfelt-Hansen, Jacob, Schwartz, Peter, Roden, Dan M., Bezzina, Connie R., Olesen, Morten, Darbar, Dawood, Guicheney, Pascale, Crotti, Lia, and Jamshidi, Yalda

Published
2015
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35. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author

Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Hege Aamodt, Anne, Heidi Skogholt, Anne, Brumpton, Ben M, Willer, Cristen J, Sandset, Else C, Kristoffersen, Espen S, Ellekjær, Hanne, Heuch, Ingrid, Nielsen, Jonas B, Hagen, Knut, Hveem, Kristian, Fritsche, Lars G, Thomas, Laurent F, Pedersen, Linda M, Gabrielsen, Maiken E, Holmen, Oddgeir L, Børte, Sigrid, Zhou, Wei, Abboud, Shérine, Pandolfo, Massimo, Thijs, Vincent, Leys, Didier, Bodenant, Marie, Louillet, Fabien, Touzé, Emmanuel, Mas, Jean-Louis, Samson, Yves, Leder, Sara, Léger, Anne, Deltour, Sandrine, Crozier, Sophie, Méresse, Isabelle, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Béjot, Yannick, Decavel, Pierre, Medeiros, Elizabeth, Montiel, Paola, Moulin, Thierry, Vuillier, Fabrice, Dallongeville, Jean, Metso, Antti J, Metso, Tiina, Tatlisumak, Turgut, Grond-Ginsbach, Caspar, Lichy, Christoph, Kloss, Manja, Werner, Inge, Arnold, Marie-Luise, Dos Santos, Michael, Grau, Armin, Dichgans, Martin, Thomas-Feles, Constanze, Weber, Ralf, Brandt, Tobias, Pezzini, Alessandro, De Giuli, Valeria, Caria, Filomena, Poli, Loris, Padovani, Alessandro, Bersano, Anna, Lanfranconi, Silvia, Beretta, Simone, Ferrarese, Carlo, Giacolone, Giacomo, Paolucci, Stefano, Lyrer, Philippe, Engelter, Stefan, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Bonati, Leo, Gensicke, Henrik, Amort, Margareth, Markus, Hugh, Majersik, Jennifer, Worrall, Bradford, Southerland, Andrew, Cole, John, Kittner, Steven, Evangelou, Evangelos, Warren, Helen R, Gao, He, Ntritsos, Georgios, Dimou, Niki, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G, Jackson, Anne U, Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian’an, Mangino, Massimo, Oldmeadow, Christopher, Peter Prins, Bram, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M, Zhao, Jing-Hua, Connell, John, de Mutsert, Renée, Doney, Alex SF, Farrall, Martin, Menni, Cristina, Morris, Andrew D, Noordam, Raymond, Paré, Guillaume, Poulter, Neil R, Shields, Denis C, Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E, Ayers, Kristin L, Barbieri, Caterina M, Batini, Chiara, Bis, Joshua C, Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Davies, Gail, de Borst, Martin H, de Geus, Eco J, Deary, Ian J, Deelen, Joris, Del Greco M, Fabiola, Yusuf Demirkale, Cumhur, Dörr, Marcus, Ehret, Georg B, Elosua, Roberto, Enroth, Stefan, Mesut Erzurumluoglu, A, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Harris, Sarah E, Hartman, Catharina A, Havulinna, Aki S, Hicks, Andrew A, Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D, Joshi, Peter K, Jousilahti, Pekka, Wouter Jukema, J, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D, Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S, Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Lehtimäki, Terho, Liewald, David CM, Lin, Li, Lind, Lars, Lindgren, Cecilia M, Liu, YongMei, Loos, Ruth JF, Lopez, Lorna M, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P, Morrison, Alanna C, Munson, Peter J, Nalls, Mike A, Nandakumar, Priyanka, Nelson, Christopher P, Niiranen, Teemu, Nolte, Ilja M, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, O’Reilly, Paul F, Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, WJH Penninx, Brenda, Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P, Tri Nguyen, Quang, Raitakari, Olli T, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M, Ried, Janina S, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M, Rotter, Jerome I, Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F, Salomaa, Veikko, Samani, Nilesh J, Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V, Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M, Stott, David J, Strachan, David P, Strawbridge, Rona J, Sundström, Johan, Swertz, Morris A, Taylor, Kent D, Teumer, Alexander, Tobin, Martin D, Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G, Vaez, Ahmad, van der Most, Peter J, van Duijn, Cornelia M, Verwoert, Germaine C, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Wilson, James F, Wright, Alan F, Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R, Butterworth, Adam S, Chasman, Daniel I, Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna MM, Laakso, Markku, Lakatta, Edward G, Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O, Palmer, Colin NA, Risch, Lorenz, Scott, Robert A, Scott, Rodney J, Sever, Peter, Spector, Tim D, van der Harst, Pim, Wareham, Nicholas J, Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B, Newton-Cheh, Christopher, Brown, Morris J, Metspalu, Andres, Psaty, Bruce M., Wain, Louise V, Elliott, Paul, Caulfield, Mark J, Gormley, Padhraig, Anttila, Verneri, Palta, Priit, Esko, Tonu, Pers, Tune H, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Ridker, Paul M, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Arfan Ikram, M, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Palotie, Aarno, Akiyama, Masato, Alg, Varinder S., Børte, Sigrid, Broderick, Joseph P., Brumpton, Ben M., Dauvillier, Jérôme, Desal, Hubert, Dina, Christian, Friedrich, Christoph M., Gaál-Paavola, Emília I., Gentric, Jean-Christophe, Hirsch, Sven, Hostettler, Isabel C., Houlden, Henry, Hveem, Kristian, Jääskeläinen, Juha E., Johnsen, Marianne Bakke, Li, Liming, Lin, Kuang, Lindgren, Antti, Martin, Olivier, Matsuda, Koichi, Millwood, Iona Y., Naggara, Olivier, Niemelä, Mika, Pera, Joanna, Redon, Richard, Rouleau, Guy A., Sandvei, Marie Søfteland, Schilling, Sabine, Shotar, Eimad, Slowik, Agnieszka, Terao, Chikashi, Verschuren, W. M. Monique, Walters, Robin G., Werring, David J., Willer, Cristen J., Woo, Daniel, Worrall, Bradford B., and Zhou, Sirui

Published
2023
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36. 87 rare variants associated with blood pressure regulation in meta-analysis of ~1.3 million individuals

Author

Surendran, Praveen, Karthikeyan, Savita, Chen, Lingyan, Prins, Bram P, Stewart, Isabel D, Foley, Christopher N, Lotta, Luca A, Luan, Jian'an, Paul, Dirk S, Staley, James, Willems, Sara M, Young, Robin, Zhao, Jing-Hua, Burgess, Stephen, Kamat, Mihir, Peters, James, Yonova-Doing, Ekaterina, Chowdhury, Rajiv, Di Angelantonio, Emanuele, Wareham, Nicholas J, Langenberg, Claudia, Butterworth, Adam S, Danesh, John, Saleheen, Danish, Howson, Joanna MM, Surendran, Praveen [0000-0002-4911-6077], Chen, Lingyan [0000-0003-3750-6761], Foley, Christopher [0000-0002-0970-2610], Luan, Jian'an [0000-0003-3137-6337], Burgess, Stephen [0000-0001-5365-8760], Chowdhury, Rajiv [0000-0003-4881-5690], Di Angelantonio, Emanuele [0000-0001-8776-6719], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository

Abstract

Genetic studies of blood pressure (BP) to date have mainly analysed common variants (minor allele frequency, MAF>0.05). In a meta-analysis of up to >1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (MAF≤0.01) variant-BP associations (P, Praveen Surendran is supported by a Rutherford Fund Fellowship from the Medical Research Council grant MR/S003746/1. Najim Lahrouchi is supported by the Foundation “De Drie Lichten” in The Netherlands and the Netherlands Cardiovascular Research Initiative, an initiative supported by the Dutch Heart Foundation (CVON2012-10 PREDICT and CVON2018-30 PREDICT2). Jacklyn N. Hellwege was supported by the Vanderbilt Molecular and Genetic Epidemiology of Cancer (MAGEC) Training Program (T32CA160056, PI X.-O. Shu). Nora Franceschini is supported by the National Institute of Health awards HL140385, MD012765 and DK117445. Folkert W. Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre. Panos Deloukas’s work was supported by the British Heart Foundation (BHF) grant RG/14/5/30893. Ruth J.F. Loos is funded by R01DK110113, U01HG007417, R01DK101855, R01DK107786. Caroline Hayward is supported by an MRC University Unit Programme Grant MC_UU_00007/10 (QTL in Health and Disease) and MRC University Unit Programme Grant MC_PC_U127592696. Mark I. McCarthy* is a Wellcome Senior Investigator (098381; 212259) and an NIHR Senior Investigator (NF-SI-0617-10090). The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), and by the Wellcome (090532, 106130, 098381, 203141, 212259). Teresa Ferreira* is supported by the NIHR Biomedical Research Centre, Oxford. Maciej Tomaszewski is supported by British Heart Foundation (PG/17/35/33001 and PG/19/16/34270) and Kidney Research UK (RP_017_20180302). John Danesh* is funded by the National Institute for Health Research [Senior Investigator Award]. Cecilia M. Lindgren* is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, Oxford, by Widenlife and NIH (5P50HD028138-27). Joanna M. M. Howson* was funded by the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. *The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Full acknowledgements are provided in the supplementary information.

Published
2020
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37. Genome-wide association study of circulating interleukin 6 levels identifies novel loci

Author

Ahluwalia, Tarunveer S., Prins, Bram P., Abdollahi, Mohammadreza, Armstrong, Nicola J., Aslibekyan, Stella, Bain, Lisa, Jefferis, Barbara, Baumert, Jens, Beekman, Marian, Ben-Shlomo, Yoav, Bis, Joshua C., Mitchell, Braxton D., de Geus, Eco, Delgado, Graciela E., Marek, Diana, Eriksson, Joel, Kajantie, Eero, Kanoni, Stavroula, Kemp, John P., Lu, Chen, Marioni, Riccardo E., McLachlan, Stela, Milaneschi, Yuri, Nolte, Ilja M., Petrelis, Alexandros M., Porcu, Eleonora, Sabater-Lleal, Maria, Naderi, Elnaz, Seppala, Ilkka, Shah, Tina, Singhal, Gaurav, Standl, Marie, Teumer, Alexander, Thalamuthu, Anbupalam, Thiering, Elisabeth, Trompet, Stella, Ballantyne, Christie M., Benjamin, Emelia J., Casas, Juan P., Toben, Catherine, Dedoussis, George, Deelen, Joris, Durda, Peter, Engmann, Jorgen, Feitosa, Mary F., Grallert, Harald, Hammarstedt, Ann, Harris, Sarah E., Homuth, Georg, Hottenga, Jouke-Jan, Jalkanen, Sirpa, Jamshidi, Yalda, Jawahar, Magdalene C., Jess, Tine, Kivimaki, Mika, Kleber, Marcus E., Lahti, Jari, Liu, Yongmei, Marques-Vidal, Pedro, Mellstrom, Dan, Mooijaart, Simon P., Muller-Nurasyid, Martina, Penninx, Brenda, Revez, Joana A., Rossing, Peter, Raikkonen, Katri, Sattar, Naveed, Scharnagl, Hubert, Sennblad, Bengt, Silveira, Angela, St Pourcain, Beate, Timpson, Nicholas J., Trollor, Julian, van Dongen, Jenny, Van Heemst, Diana, Visvikis-Siest, Sophie, Vollenweider, Peter, Volker, Uwe, Waldenberger, Melanie, Willemsen, Gonneke, Zabaneh, Delilah, Morris, Richard W., Arnett, Donna K., Baune, Bernhard T., Boomsma, Dorret, I, Chang, Yen-Pei C., Deary, Ian J., Deloukas, Panos, Eriksson, Johan G., Evans, David M., Ferreira, Manuel A., Gaunt, Tom, Gudnason, Vilmundur, Hamsten, Anders, Heinrich, Joachim, Hingorani, Aroon, Humphries, Steve E., Jukema, J. Wouter, Koenig, Wolfgang, Kumari, Meena, Kutalik, Zoltan, Lawlor, Deborah A., Lehtimaki, Terho, Marz, Winfried, Mather, Karen A., Naitza, Silvia, Nauck, Matthias, Ohlsson, Claes, Price, Jackie F., Raitakari, Olli, Rice, Ken, Sachdev, Perminder S., Slagboom, Eline, Sorensen, Thorkild I. A., Spector, Tim, Stacey, David, Stathopoulou, Maria G., Tanaka, Toshiko, Wannamethee, S. Goya, Whincup, Peter, Rotter, Jerome, I, Dehghan, Abbas, Boerwinkle, Eric, Psaty, Bruce M., Snieder, Harold, Alizadeh, Behrooz Z., Ahluwalia, Tarunveer S., Prins, Bram P., Abdollahi, Mohammadreza, Armstrong, Nicola J., Aslibekyan, Stella, Bain, Lisa, Jefferis, Barbara, Baumert, Jens, Beekman, Marian, Ben-Shlomo, Yoav, Bis, Joshua C., Mitchell, Braxton D., de Geus, Eco, Delgado, Graciela E., Marek, Diana, Eriksson, Joel, Kajantie, Eero, Kanoni, Stavroula, Kemp, John P., Lu, Chen, Marioni, Riccardo E., McLachlan, Stela, Milaneschi, Yuri, Nolte, Ilja M., Petrelis, Alexandros M., Porcu, Eleonora, Sabater-Lleal, Maria, Naderi, Elnaz, Seppala, Ilkka, Shah, Tina, Singhal, Gaurav, Standl, Marie, Teumer, Alexander, Thalamuthu, Anbupalam, Thiering, Elisabeth, Trompet, Stella, Ballantyne, Christie M., Benjamin, Emelia J., Casas, Juan P., Toben, Catherine, Dedoussis, George, Deelen, Joris, Durda, Peter, Engmann, Jorgen, Feitosa, Mary F., Grallert, Harald, Hammarstedt, Ann, Harris, Sarah E., Homuth, Georg, Hottenga, Jouke-Jan, Jalkanen, Sirpa, Jamshidi, Yalda, Jawahar, Magdalene C., Jess, Tine, Kivimaki, Mika, Kleber, Marcus E., Lahti, Jari, Liu, Yongmei, Marques-Vidal, Pedro, Mellstrom, Dan, Mooijaart, Simon P., Muller-Nurasyid, Martina, Penninx, Brenda, Revez, Joana A., Rossing, Peter, Raikkonen, Katri, Sattar, Naveed, Scharnagl, Hubert, Sennblad, Bengt, Silveira, Angela, St Pourcain, Beate, Timpson, Nicholas J., Trollor, Julian, van Dongen, Jenny, Van Heemst, Diana, Visvikis-Siest, Sophie, Vollenweider, Peter, Volker, Uwe, Waldenberger, Melanie, Willemsen, Gonneke, Zabaneh, Delilah, Morris, Richard W., Arnett, Donna K., Baune, Bernhard T., Boomsma, Dorret, I, Chang, Yen-Pei C., Deary, Ian J., Deloukas, Panos, Eriksson, Johan G., Evans, David M., Ferreira, Manuel A., Gaunt, Tom, Gudnason, Vilmundur, Hamsten, Anders, Heinrich, Joachim, Hingorani, Aroon, Humphries, Steve E., Jukema, J. Wouter, Koenig, Wolfgang, Kumari, Meena, Kutalik, Zoltan, Lawlor, Deborah A., Lehtimaki, Terho, Marz, Winfried, Mather, Karen A., Naitza, Silvia, Nauck, Matthias, Ohlsson, Claes, Price, Jackie F., Raitakari, Olli, Rice, Ken, Sachdev, Perminder S., Slagboom, Eline, Sorensen, Thorkild I. A., Spector, Tim, Stacey, David, Stathopoulou, Maria G., Tanaka, Toshiko, Wannamethee, S. Goya, Whincup, Peter, Rotter, Jerome, I, Dehghan, Abbas, Boerwinkle, Eric, Psaty, Bruce M., Snieder, Harold, and Alizadeh, Behrooz Z.

Abstract

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Published
2021
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38. Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci

Author

Ahluwalia, Tarunveer S, Prins, Bram P, Abdollahi, Mohammadreza, Armstrong, Nicola J, Aslibekyan, Stella, Bain, Lisa, Jefferis, Barbara, Baumert, Jens, Beekman, Marian, Ben-Shlomo, Yoav, Bis, Joshua C, Mitchell, Braxton D, de Geus, Eco, Delgado, Graciela E, Marek, Diana, Eriksson, Joel, Kajantie, Eero, Kanoni, Stavroula, Kemp, John P, Lu, Chen, Marioni, Riccardo E, McLachlan, Stela, Milaneschi, Yuri, Nolte, Ilja M, Petrelis, Alexandros M, Porcu, Eleonora, Sabater-Lleal, Maria, Naderi, Elnaz, Seppälä, Ilkka, Shah, Tina, Singhal, Gaurav, Standl, Marie, Teumer, Alexander, Thalamuthu, Anbupalam, Thiering, Elisabeth, Trompet, Stella, Ballantyne, Christie M, Benjamin, Emelia J, Casas, Juan P, Toben, Catherine, Dedoussis, George, Deelen, Joris, Durda, Peter, Engmann, Jorgen, Feitosa, Mary F, Grallert, Harald, Hammarstedt, Ann, Jess, Tine, Rossing, Peter, Sørensen, Thorkild I A, Ahluwalia, Tarunveer S, Prins, Bram P, Abdollahi, Mohammadreza, Armstrong, Nicola J, Aslibekyan, Stella, Bain, Lisa, Jefferis, Barbara, Baumert, Jens, Beekman, Marian, Ben-Shlomo, Yoav, Bis, Joshua C, Mitchell, Braxton D, de Geus, Eco, Delgado, Graciela E, Marek, Diana, Eriksson, Joel, Kajantie, Eero, Kanoni, Stavroula, Kemp, John P, Lu, Chen, Marioni, Riccardo E, McLachlan, Stela, Milaneschi, Yuri, Nolte, Ilja M, Petrelis, Alexandros M, Porcu, Eleonora, Sabater-Lleal, Maria, Naderi, Elnaz, Seppälä, Ilkka, Shah, Tina, Singhal, Gaurav, Standl, Marie, Teumer, Alexander, Thalamuthu, Anbupalam, Thiering, Elisabeth, Trompet, Stella, Ballantyne, Christie M, Benjamin, Emelia J, Casas, Juan P, Toben, Catherine, Dedoussis, George, Deelen, Joris, Durda, Peter, Engmann, Jorgen, Feitosa, Mary F, Grallert, Harald, Hammarstedt, Ann, Jess, Tine, Rossing, Peter, and Sørensen, Thorkild I A

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery, and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed-effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on Chromosome (Chr) 2q14, (pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Published
2021

39. Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19

Author

Gaziano, Liam, primary, Giambartolomei, Claudia, additional, Pereira, Alexandre C, additional, Gaulton, Anna, additional, Posner, Daniel C, additional, Swanson, Sonja A, additional, Ho, Yuk-Lam, additional, Iyengar, Sudha K, additional, Kosik, Nicole M, additional, Vujkovic, Marijana, additional, Gagnon, David R, additional, Bento, A Patrícia, additional, Beltrao, Pedro, additional, Barrio-Hernandez, Inigo, additional, Rönnblom, Lars, additional, Hagberg, Niklas, additional, Lundtoft, Christian, additional, Langenberg, Claudia, additional, Pietzner, Maik, additional, Valentine, Dennis, additional, Allara, Elias, additional, Surendran, Praveen, additional, Burgess, Stephen, additional, Zhao, Jing Hua, additional, Peters, James E, additional, Prins, Bram P, additional, Danesh, John, additional, Devineni, Poornima, additional, Shi, Yunling, additional, Lynch, Kristine E, additional, DuVall, Scott L, additional, Garcon, Helene, additional, Thomann, Lauren O, additional, Zhou, Jin J, additional, Gorman, Bryan R, additional, Huffman, Jennifer E, additional, O’Donnell, Christopher J, additional, Tsao, Philip S, additional, Beckham, Jean C, additional, Pyarajan, Saiju, additional, Muralidhar, Sumitra, additional, Huang, Grant D, additional, Ramoni, Rachel, additional, Hung, Adriana M, additional, Chang, Kyong-Mi, additional, Sun, Yan V, additional, Joseph, Jacob, additional, Leach, Andrew R, additional, Edwards, Todd L, additional, Cho, Kelly, additional, Gaziano, J Michael, additional, Butterworth, Adam S, additional, and Casas, Juan P, additional

Published
2020
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41. Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes: A Large-Scale Cross-Consortium Mendelian Randomization Study

Author

Prins, Bram. P., Abbasi, Ali, Wong, Anson, Vaez, Ahmad, Nolte, Ilja, Franceschini, Nora, Stuart, Philip E., Guterriez Achury, Javier, Mistry, Vanisha, Bradfield, Jonathan P., Valdes, Ana M., Bras, Jose, Shatunov, Aleksey, Lu, Chen, Han, Buhm, Raychaudhuri, Soumya, Bevan, Steve, Mayes, Maureen D., Tsoi, Lam C., Evangelou, Evangelos, Nair, Rajan P., Grant, Struan F. A., Polychronakos, Constantin, Radstake, Timothy R. D., van Heel, David A., Dunstan, Melanie L., Wood, Nicholas W., Al-Chalabi, Ammar, Dehghan, Abbas, Hakonarson, Hakon, Markus, Hugh S., Elder, James T., Knight, Jo, Arking, Dan E., Spector, Timothy D., Koeleman, Bobby P. C., van Duijn, Cornelia M., Martin, Javier, Morris, Andrew P., Weersma, Rinse K., Wijmenga, Cisca, Munroe, Patricia B., Perry, John R. B., Pouget, Jennie G., Jamshidi, Yalda, Snieder, Harold, and Alizadeh, Behrooz Z.

Subjects
Analysis, Research, Risk factors, Mental disorders -- Risk factors -- Research, Outcome and process assessment (Medical care) -- Analysis, C-reactive protein -- Investigations -- Analysis -- Research
Abstract

Author(s): Bram. P. Prins 1,2,*, Ali Abbasi 1,3,4, Anson Wong 5,6, Ahmad Vaez 1,7, Ilja Nolte 1, Nora Franceschini 8, Philip E. Stuart 9, Javier Guterriez Achury 10, Vanisha Mistry [...], Background C-reactive protein (CRP) is associated with immune, cardiometabolic, and psychiatric traits and diseases. Yet it is inconclusive whether these associations are causal. Methods and Findings We performed Mendelian randomization (MR) analyses using two genetic risk scores (GRSs) as instrumental variables (IVs). The first GRS consisted of four single nucleotide polymorphisms (SNPs) in the CRP gene (GRS.sub.CRP ), and the second consisted of 18 SNPs that were significantly associated with CRP levels in the largest genome-wide association study (GWAS) to date (GRS.sub.GWAS). To optimize power, we used summary statistics from GWAS consortia and tested the association of these two GRSs with 32 complex somatic and psychiatric outcomes, with up to 123,865 participants per outcome from populations of European ancestry. We performed heterogeneity tests to disentangle the pleiotropic effect of IVs. A Bonferroni-corrected significance level of less than 0.0016 was considered statistically significant. An observed p-value equal to or less than 0.05 was considered nominally significant evidence for a potential causal association, yet to be confirmed. The strengths (F-statistics) of the IVs were 31.92-3,761.29 and 82.32-9,403.21 for GRS.sub.CRP and GRS.sub.GWAS, respectively. CRP GRS.sub.GWAS showed a statistically significant protective relationship of a 10% genetically elevated CRP level with the risk of schizophrenia (odds ratio [OR] 0.86 [95% CI 0.79-0.94]; p < 0.001). We validated this finding with individual-level genotype data from the schizophrenia GWAS (OR 0.96 [95% CI 0.94-0.98]; p < 1.72 x 10.sup.-6). Further, we found that a standardized CRP polygenic risk score (CRP.sub.PRS) at p-value thresholds of 1 x 10.sup.-4, 0.001, 0.01, 0.05, and 0.1 using individual-level data also showed a protective effect (OR < 1.00) against schizophrenia; the first CRP.sub.PRS (built of SNPs with p < 1 x 10.sup.-4) showed a statistically significant (p < 2.45 x 10.sup.-4) protective effect with an OR of 0.97 (95% CI 0.95-0.99). The CRP GRS.sub.GWAS showed that a 10% increase in genetically determined CRP level was significantly associated with coronary artery disease (OR 0.88 [95% CI 0.84-0.94]; p < 2.4 x 10.sup.-5) and was nominally associated with the risk of inflammatory bowel disease (OR 0.85 [95% CI 0.74-0.98]; p < 0.03), Crohn disease (OR 0.81 [95% CI 0.70-0.94]; p < 0.005), psoriatic arthritis (OR 1.36 [95% CI 1.00-1.84]; p < 0.049), knee osteoarthritis (OR 1.17 [95% CI 1.01-1.36]; p < 0.04), and bipolar disorder (OR 1.21 [95% CI 1.05-1.40]; p < 0.007) and with an increase of 0.72 (95% CI 0.11-1.34; p < 0.02) mm Hg in systolic blood pressure, 0.45 (95% CI 0.06-0.84; p < 0.02) mm Hg in diastolic blood pressure, 0.01 ml/min/1.73 m.sup.2 (95% CI 0.003-0.02; p < 0.005) in estimated glomerular filtration rate from serum creatinine, 0.01 g/dl (95% CI 0.0004-0.02; p < 0.04) in serum albumin level, and 0.03 g/dl (95% CI 0.008-0.05; p < 0.009) in serum protein level. However, after adjustment for heterogeneity, neither GRS showed a significant effect of CRP level (at p < 0.0016) on any of these outcomes, including coronary artery disease, nor on the other 20 complex outcomes studied. Our study has two potential limitations: the limited variance explained by our genetic instruments modeling CRP levels in blood and the unobserved bias introduced by the use of summary statistics in our MR analyses. Conclusions Genetically elevated CRP levels showed a significant potentially protective causal relationship with risk of schizophrenia. We observed nominal evidence at an observed p < 0.05 using either GRS.sub.CRP or GRS.sub.GWAS -with persistence after correction for heterogeneity-for a causal relationship of elevated CRP levels with psoriatic osteoarthritis, rheumatoid arthritis, knee osteoarthritis, systolic blood pressure, diastolic blood pressure, serum albumin, and bipolar disorder. These associations remain yet to be confirmed. We cannot verify any causal effect of CRP level on any of the other common somatic and neuropsychiatric outcomes investigated in the present study. This implies that interventions that lower CRP level are unlikely to result in decreased risk for the majority of common complex outcomes.

Published
2016
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42. A catalog of genetic loci associated with kidney function from analyses of a million individuals

Author

Wuttke, Matthias, Li, Yong, Li, Man, Sieber, Karsten B., Feitosa, Mary F., Gorski, Mathias, Tin, Adrienne, Wang, Lihua, Chu, Audrey Y., Hoppmann, Anselm, Kirsten, Holger, Giri, Ayush, Chai, Jin-Fang, Sveinbjornsson, Gardar, Tayo, Bamidele O., Nutile, Teresa, Fuchsberger, Christian, Marten, Jonathan, Cocca, Massimiliano, Ghasemi, Sahar, Xu, Yizhe, Horn, Katrin, Noce, Damia, van der Most, Peter J., Sedaghat, Sanaz, Yu, Zhi, Akiyama, Masato, Afaq, Saima, Ahluwalia, Tarunveer S., Almgren, Peter, Amin, Najaf, Ärnlöv, Johan, Bakker, Stephan J. L., Bansal, Nisha, Baptista, Daniela, Bergmann, Sven, Biggs, Mary L., Biino, Ginevra, Boehnke, Michael, Boerwinkle, Eric, Boissel, Mathilde, Bottinger, Erwin P., Boutin, Thibaud S., Brenner, Hermann, Brumat, Marco, Burkhardt, Ralph, Butterworth, Adam S., Campana, Eric, Campbell, Archie, Campbell, Harry, Canouil, Mickaël, Carroll, Robert J., Catamo, Eulalia, Chambers, John C., Chee, Miao-Ling, Chee, Miao-Li, Chen, Xu, Cheng, Ching-Yu, Cheng, Yurong, Christensen, Kaare, Cifkova, Renata, Ciullo, Marina, Pina Concas, Maria, Cook, James P., Coresh, Josef, Corre, Tanguy, Sala, Cinzia Felicita, Cusi, Daniele, Danesh, John, Daw, E. Warwick, de Borst, Martin H., De Grandi, Alessandro, de Mutsert, Renée, de Vries, Aiko P. J., Degenhardt, Frauke, Delgado, Graciela, Demirkan, Ayse, Di Angelantonio, Emanuele, Dittrich, Katalin, Divers, Jasmin, Dorajoo, Rajkumar, Eckardt, Kai-Uwe, Ehret, Georg, Elliott, Paul, Endlich, Karlhans, Evans, Michele K., Felix, Janine F., Foo, Valencia Hui Xian, Franco, Oscar H., Franke, Andre, Freedman, Barry I., Freitag-Wolf, Sandra, Friedlander, Yechiel, Froguel, Philippe, Gansevoort, Ron T., Gao, He, Gasparini, Paolo, Gaziano, J. Michael, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Giulianini, Franco, Gögele, Martin, Gordon, Scott D., Gudbjartsson, Daniel F., Gudnason, Vilmundur, Haller, Toomas, Hamet, Pavel, Harris, Tamara B., Hartman, Catharina A., Hayward, Caroline, Hellwege, Jacklyn N., Heng, Chew-Kiat, Hickst, Andrew A., Hofer, Edith, Huang, Wei, Hutri-Kähönen, Nina, Hwang, Shih-Jen, ikram, M. Arfan, indridason, Olafur S., Ingelsson, Erik, ising, Marcus, Jaddoe, Vincent W. V., Jakobsdottir, Johanna, Jonas, Jost B, Joshi, Peter K., Shilpa Josyula, Navya, Jung, Bettina, Kähönen, Mika, Kamatani, Yoichiro, Kammerer, Candace M., Kanai, Masahiro, Kastarinen, Mika, Kerr, Shona M., Khor, Chiea-Chuen, Kiess, Wieland, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kraja, Aldi T., Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard K., Kronenberg, Florian, Kubo, Michiaki, Kühnel, Brigitte, Kuokkanen, Mikko, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lange, Leslie A., Langefeld, Carl D., Jen-Mai Lee, Jeannette, Lehne, Benjamin, Lehtimäki, Terho, Lieb, Wolfgang, Cohort Study, Lifelines, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jun, Liu, Jianjun, Loeffler, Markus, Loos, Ruth J. F., Lucae, Susanne, Ann Lukas, Mary, Lyytikäinen, Leo-Pekka, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Martins, Jade, März, Winfried, Mascalzoni, Deborah, Matsuda, Koichi, Christa Meisinger, Meitinger, Thomas, Melander, Olle, Metspalu, Andres, Mikaelsdottir, Evgenia K., Milaneschi, Yuri, Miliku, Kozeta, Mishra, Pashupati P., Veteran Program, V. A. Million, Mohlke, Karen L., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mychaleckyj, Josyf C., Nadkarni, Girish N, Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, ilja M., Noordam, Raymond, O’Connell, Jeffrey, O’Donoghue, Michelle L., Olafsson, Isleifur, Oldehinkel, Albertine J., Orho-Melander, Marju, Ouwehand, Willem H., Padmanabhan, Sandosh, Palmer, Nicholette D., Palsson, Runolfur, Penninx, Brenda W. J. H., Perls, Thomas, Perola, Markus, Pirastu, Mario, Pirastu, Nicola, Pistis, Giorgio, Podgornaia, Anna I., Polasek, Ozren, Ponte, Belen, Porteous, David J., Poulain, Tanja, Pramstaller, Peter P., Preuss, Michael H., Prins, Bram P., Province, Michael A., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Reilly, Dermot F., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Ridker, Paul M., Rivadeneira, Fernando, Rizzi, Federica, Roberts, David J., Robino, Antonietta, Rossing, Peter, Rudan, Igor, Rueedi, Rico, Ruggiero, Daniela, Ryan, Kathleen A., Saba, Yasaman, Sabanayagam, Charumathi, Salomaa, Veikko, Salvi, Erika, Saum, Kai-Uwe, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Schupf, Nicole, Shaffer, Christian M., Shi, Yuan, Smith, Albert V., Smith, Blair H., Soranzo, Nicole, Spracklen, Cassandra N., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Svensson, Per O., Szymczak, Silke, Tai, E-Shyong, Tajuddin, Salman M., Tan, Nicholas Y. Q., Taylor, Kent D., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomsen, Hauke, Thorleifsson, Gudmar, Toniolo, Daniela, Tönjes, Anke, Tremblay, Johanne, Tzoulaki, Ioanna, Uitterlinden, André G., Vaccargiu, Simona, van Dam, Rob M., van der Harst, Pim, van Duijn, Cornelia M., Velez Edward, Digna R., Verweij, Niek, Vogelezang, suzanne, Völker, üwe, Vollenweider, Peter, Waeber, Gerard, Waldenberger, Melanie, Wallentin, Lars, Wang, Ya Xing, Wang, Chaolong, Waterworth, Dawn M., Bin Wei, Wen, White, Harvey, Whitfield, John B., Wild, Sarah H., Wilson, James F., Wojczynski, Mary K., Wong, Charlene, Wong, Tien-Yin, Xu, Liang, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Weihua, Zonderman, Alan B., Rotter, Jerome I., Bochud, Murielle, Psaty, Bruce M., Vitart, Veronique, Wilson, James G., Dehghan, Abbas, Parsa, Afshin, Chasman, Daniel I., Ho, Kevin, Morris, Andrew P., Devuyst, Olivier, Akilesh, Shreeram, Pendergrass, Sarah A., Sim, Xueling, Böger, Carsten A., Okada, Yukinori, Edwards, Todd L., Snieder, Harold, Stefansson, Kari, Hung, Adriana M., Heid, Iris M., Markus Scholz, Teumer, Alexander, Köttgen, Anna, Pattaro, Cristian, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Internal Medicine, Epidemiology, Erasmus MC other, Pediatrics, Psychiatry, APH - Mental Health, APH - Digital Health, Wuttke, M, Li, Y, Li, M, Sieber, Kb, Feitosa, Mf, Gorski, M, Tin, A, Wang, L, Chu, Ay, Hoppmann, A, Kirsten, H, Giri, A, Chai, Jf, Sveinbjornsson, G, Tayo, Bo, Nutile, T, Fuchsberger, C, Marten, J, Cocca, M, Ghasemi, S, Xu, Y, Horn, K, Noce, D, van der Most, Pj, Sedaghat, S, Yu, Z, Akiyama, M, Afaq, S, Ahluwalia, T, Almgren, P, Amin, N, Ärnlöv, J, Bakker, Sjl, Bansal, N, Baptista, D, Bergmann, S, Biggs, Ml, Biino, G, Boehnke, M, Boerwinkle, E, Boissel, M, Bottinger, Ep, Boutin, T, Brenner, H, Brumat, M, Burkhardt, R, Butterworth, A, Campana, Eric, Campbell, A, Campbell, H, Canouil, M, Carroll, Rj, Catamo, E, Chambers, Jc, Chee, Ml, Chen, X, Cheng, Cy, Cheng, Y, Christensen, K, Cifkova, R, Ciullo, M, Concas, Mp, Cook, Jp, Coresh, J, Corre, T, Sala, Cf, Cusi, D, Danesh, J, Daw, Ew, de Borst, Mh, De Grandi, A, de Mutsert, R, de Vries, Apj, Degenhardt, F, Delgado, G, Demirkan, A, Di Angelantonio, E, Dittrich, K, Divers, J, Dorajoo, R, Eckardt, Ku, Ehret, G, Elliott, P, Endlich, K, Evans, Mk, Felix, Jf, Foo, Vhx, Franco, Oh, Franke, A, Freedman, Bi, Freitag-Wolf, S, Friedlander, Y, Froguel, P, Gansevoort, Rt, Gao, H, Gasparini, P, Gaziano, Jm, Giedraitis, V, Gieger, C, Girotto, G, Giulianini, F, Gögele, M, Gordon, Sd, Gudbjartsson, Df, Gudnason, V, Haller, T, Hamet, P, Harris, Tb, Hartman, Ca, Hayward, C, Hellwege, Jn, Heng, Ck, Hicks, Aa, Hofer, E, Huang, W, Hutri-Kähönen, N, Hwang, Sj, Ikram, Ma, Indridason, O, Ingelsson, E, Ising, M, Jaddoe, Vwv, Jakobsdottir, J, Jonas, Jb, Joshi, Pk, Josyula, N, Jung, B, Kähönen, M, Kamatani, Y, Kammerer, Cm, Kanai, M, Kastarinen, M, Kerr, Sm, Khor, Cc, Kiess, W, Kleber, Me, Koenig, W, Kooner, J, Körner, A, Kovacs, P, Kraja, At, Krajcoviechova, A, Kramer, H, Krämer, Bk, Kronenberg, F, Kubo, M, Kühnel, B, Kuokkanen, M, Kuusisto, J, La Bianca, M, Laakso, M, Lange, La, Langefeld, Cd, Lee, Jj, Lehne, B, Lehtimäki, T, Lieb, W, Lifelines Cohort, Study, Lim, Sc, Lind, L, Lindgren, Cm, Liu, J, Loeffler, M, Loos, Rjf, Lucae, S, Lukas, Ma, Lyytikäinen, Lp, Mägi, R, Magnusson, Pke, Mahajan, A, Martin, Ng, Martins, J, März, W, Mascalzoni, D, Matsuda, K, Meisinger, C, Meitinger, T, Melander, O, Metspalu, A, Mikaelsdottir, Ek, Milaneschi, Y, Miliku, K, Mishra, Pp, V. A., Million Veteran Program, Mohlke, Kl, Mononen, N, Montgomery, Gw, Mook-Kanamori, Do, Mychaleckyj, Jc, Nadkarni, Gn, Nalls, Ma, Nauck, M, Nikus, K, Ning, B, Nolte, Im, Noordam, R, O'Connell, J, O'Donoghue, Ml, Olafsson, I, Oldehinkel, Aj, Orho-Melander, M, Ouwehand, Wh, Padmanabhan, S, Palmer, Nd, Palsson, R, Penninx, Bwjh, Perls, T, Perola, M, Pirastu, M, Pirastu, N, Pistis, G, Podgornaia, Ai, Polasek, O, Ponte, B, Porteous, Dj, Poulain, T, Pramstaller, Pp, Preuss, Mh, Prins, Bp, Province, Ma, Rabelink, Tj, Raffield, Lm, Raitakari, Ot, Reilly, Df, Rettig, R, Rheinberger, M, Rice, Km, Ridker, Pm, Rivadeneira, F, Rizzi, F, Roberts, Dj, Robino, A, Rossing, P, Rudan, I, Rueedi, R, Ruggiero, D, Ryan, Ka, Saba, Y, Sabanayagam, C, Salomaa, V, Salvi, E, Saum, Ku, Schmidt, H, Schmidt, R, Schöttker, B, Schulz, Ca, Schupf, N, Shaffer, Cm, Shi, Y, Smith, Av, Smith, Bh, Soranzo, N, Spracklen, Cn, Strauch, K, Stringham, Hm, Stumvoll, M, Svensson, Po, Szymczak, S, Tai, E, Tajuddin, Sm, Tan, Nyq, Taylor, Kd, Teren, A, Tham, Yc, Thiery, J, Thio, Chl, Thomsen, H, Thorleifsson, G, Toniolo, D, Tönjes, A, Tremblay, J, Tzoulaki, I, Uitterlinden, Ag, Vaccargiu, S, van Dam, Rm, van der Harst, P, van Duijn, Cm, Velez Edward, Dr, Verweij, N, Vogelezang, S, Völker, U, Vollenweider, P, Waeber, G, Waldenberger, M, Wallentin, L, Wang, Yx, Wang, C, Waterworth, Dm, Bin Wei, W, White, H, Whitfield, Jb, Wild, Sh, Wilson, Jf, Wojczynski, Mk, Wong, C, Wong, Ty, Xu, L, Yang, Q, Yasuda, M, Yerges-Armstrong, Lm, Zhang, W, Zonderman, Ab, Rotter, Ji, Bochud, M, Psaty, Bm, Vitart, V, Wilson, Jg, Dehghan, A, Parsa, A, Chasman, Di, Ho, K, Morris, Ap, Devuyst, O, Akilesh, S, Pendergrass, Sa, Sim, X, Böger, Ca, Okada, Y, Edwards, Tl, Snieder, H, Stefansson, K, Hung, Am, Heid, Im, Scholz, M, Teumer, A, Köttgen, A, and Pattaro, C.

Subjects
catalog, Inheritance Patterns, Hasso-Plattner-Institut für Digital Engineering GmbH, Genome-wide association study, Disease, Kidney Function Tests, Bioinformatics, DISEASE, 0302 clinical medicine, Uromodulin/urine, kidney function, 11 Medical and Health Sciences, Genetics & Heredity, ddc:616, 0303 health sciences, Kidney, Genome-wide association, HERITABILITY, GENOME-WIDE ASSOCIATION, COMMON VARIANTS, RENAL-FUNCTION, TRANS-EQTLS, METAANALYSIS, TRANSPORTER, CLASSIFICATION, INTEGRATION, Chromosome Mapping, 3. Good health, Phenotype, medicine.anatomical_structure, Medical genetics, Common variants, Renal function, Trans-EQTLS, Metaanalysis, Heritability, Transporter, Life Sciences & Biomedicine, Glomerular Filtration Rate, Metaanalysi, medicine.medical_specialty, Genotype, European Continental Ancestry Group, Quantitative Trait Loci, Common variant, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, White People, V. A. Million Veteran Program, 03 medical and health sciences, Quantitative Trait, Heritable, Lifelines Cohort Study, Uromodulin, Genetics, medicine, Humans, Genetic Predisposition to Disease, Renal Insufficiency, Chronic, Genetic Association Studies, 030304 developmental biology, Genetic association, Science & Technology, urogenital system, association, genetic loci, 06 Biological Sciences, medicine.disease, Renal Insufficiency, Chronic/genetics/physiopathology/urine, Genetic Association Studies/methods, ddc:000, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study, Kidney disease
Abstract

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

Published
2019
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44. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Author

Surendran, Praveen, Feofanova, Elena V, Lahrouchi, Najim, Ntalla, Ioanna, Karthikeyan, Savita, Cook, James, Chen, Lingyan, Mifsud, Borbala, Yao, Chen, Kraja, Aldi T, Cartwright, James H, Hellwege, Jacklyn N, Giri, Ayush, Tragante, Vinicius, Thorleifsson, Gudmar, Liu, Dajiang J, Prins, Bram P, Stewart, Isobel D, Cabrera, Claudia P, Eales, James M, Akbarov, Artur, Auer, Paul L, Bielak, Lawrence F, Bis, Joshua C, Braithwaite, Vickie S, Brody, Jennifer A, Daw, E Warwick, Warren, Helen R, Drenos, Fotios, Nielsen, Sune Fallgaard, Faul, Jessica D, Fauman, Eric B, Fava, Cristiano, Ferreira, Teresa, Foley, Christopher N, Franceschini, Nora, Gao, He, Giannakopoulou, Olga, Giulianini, Franco, Gudbjartsson, Daniel F, Guo, Xiuqing, Harris, Sarah E, Havulinna, Aki S, Helgadottir, Anna, Huffman, Jennifer E, Hwang, Shih-Jen, Kanoni, Stavroula, Kontto, Jukka, Larson, Martin G, Li-Gao, Ruifang, Lindström, Jaana, Lotta, Luca A, Lu, Yingchang, Luan, Jian'an, Mahajan, Anubha, Malerba, Giovanni, Masca, Nicholas G D, Mei, Hao, Menni, Cristina, Mook-Kanamori, Dennis O, Mosen-Ansorena, David, Müller-Nurasyid, Martina, Paré, Guillaume, Paul, Dirk S, Perola, Markus, Poveda, Alaitz, Rauramaa, Rainer, Richard, Melissa, Richardson, Tom G, Sepúlveda, Nuno, Sim, Xueling, Smith, Albert V, Smith, Jennifer A, Staley, James R, Stanáková, Alena, Sulem, Patrick, Thériault, Sébastien, Thorsteinsdottir, Unnur, Trompet, Stella, Varga, Tibor V, Velez Edwards, Digna R, Veronesi, Giovanni, Weiss, Stefan, Willems, Sara M, Yao, Jie, Young, Robin, Yu, Bing, Zhang, Weihua, Zhao, Jing-Hua, Zhao, Wei, Evangelou, Evangelos, Aeschbacher, Stefanie, Asllanaj, Eralda, Blankenberg, Stefan, Bonnycastle, Lori L, Bork-Jensen, Jette, Brandslund, Ivan, Braund, Peter S, Burgess, Stephen, Cho, Kelly, Christensen, Cramer, Connell, John, Mutsert, Renée de, Dominiczak, Anna F, Dörr, Marcus, Eiriksdottir, Gudny, Farmaki, Aliki-Eleni, Gaziano, J Michael, Grarup, Niels, Grove, Megan L, Hallmans, Göran, Hansen, Torben, Have, Christian T, Heiss, Gerardo, Jørgensen, Marit E, Jousilahti, Pekka, Kajantie, Eero, Kamat, Mihir, Käräjämäki, AnneMari, Karpe, Fredrik, Koistinen, Heikki A, Kovesdy, Csaba P, Kuulasmaa, Kari, Laatikainen, Tiina, Lannfelt, Lars, Lee, I-Te, Lee, Wen-Jane, Linneberg, Allan, Martin, Lisa W, Moitry, Marie, Nadkarni, Girish, Neville, Matt J, Palmer, Colin N A, Papanicolaou, George J, Pedersen, Oluf, Peters, James, Poulter, Neil, Rasheed, Asif, Rasmussen, Katrine L, Rayner, N William, Mägi, Reedik, Renström, Frida, Rettig, Rainer, Rossouw, Jacques, Schreiner, Pamela J, Sever, Peter S, Sigurdsson, Emil L, Skaaby, Tea, Sun, Yan V, Sundström, Johan, Thorgeirsson, Gudmundur, Esko, Tõnu, Trabetti, Elisabetta, Tsao, Philip S, Tuomi, Tiinamaija, Turner, Stephen T, Tzoulaki, Ioanna, Vaartjes, Ilonca, Vergnaud, Anne-Claire, Willer, Cristen J, Wilson, Peter W F, Witte, Daniel R, Yonova-Doing, Ekaterina, Zhang, He, Aliya, Naheed, Almgren, Peter, Amouyel, Philippe, Asselbergs, Folkert W, Barnes, Michael R, Blakemore, Alexandra I, Boehnke, Michael, Bots, Michiel L, Bottinger, Erwin P, Buring, Julie E, Chambers, John C, Chen, Yii-Der Ida, Chowdhury, Rajiv, Conen, David, Correa, Adolfo, Davey Smith, George, Boer, Rudolf A de, Deary, Ian J, Dedoussis, George, Deloukas, Panos, Di Angelantonio, Emanuele, Elliott, Paul, Felix, Stephan B, Ferrières, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W, Franks, Stephen, Frossard, Philippe, Gambaro, Giovanni, Gaunt, Tom R, Groop, Leif, Gudnason, Vilmundur, Harris, Tamara B, Hayward, Caroline, Hennig, Branwen J, Herzig, Karl-Heinz, Ingelsson, Erik, Tuomilehto, Jaakko, Järvelin, Marjo-Riitta, Jukema, J Wouter, Kardia, Sharon L R, Kee, Frank, Kooner, Jaspal S, Kooperberg, Charles, Launer, Lenore J, Lind, Lars, Loos, Ruth J F, Majumder, Abdulla Al Shafi, Laakso, Markku, McCarthy, Mark I, Melander, Olle, Mohlke, Karen L, Murray, Alison D, Nordestgaard, Børge Grønne, Orho-Melander, Marju, Packard, Chris J, Padmanabhan, Sandosh, Palmas, Walter, Polasek, Ozren, Porteous, David J, Prentice, Andrew M, Province, Michael A, Relton, Caroline L, Rice, Kenneth, Ridker, Paul M, Rolandsson, Olov, Rosendaal, Frits R, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J, Sattar, Naveed, Sheu, Wayne H-H, Smith, Blair H, Soranzo, Nicole, Spector, Timothy D, Starr, John M, Sebert, Sylvain, Taylor, Kent D, Lakka, Timo A, Timpson, Nicholas J, Tobin, Martin D, van der Harst, Pim, van der Meer, Peter, Ramachandran, Vasan S, Verweij, Niek, Virtamo, Jarmo, Völker, Uwe, Weir, David R, Zeggini, Eleftheria, Charchar, Fadi J, Wareham, Nicholas J, Langenberg, Claudia, Tomaszewski, Maciej, Butterworth, Adam S, Caulfield, Mark J, Danesh, John, Edwards, Todd L, Holm, Hilma, Hung, Adriana M, Lindgren, Cecilia M, Liu, Chunyu, Manning, Alisa K, Morris, Andrew P, Morrison, Alanna C, O'Donnell, Christopher J, Psaty, Bruce M, Saleheen, Danish, Stefansson, Kari, Boerwinkle, Eric, Chasman, Daniel I, Levy, Daniel, Newton-Cheh, Christopher, Munroe, Patricia B, Howson, Joanna M M, Surendran, Praveen, Feofanova, Elena V, Lahrouchi, Najim, Ntalla, Ioanna, Karthikeyan, Savita, Cook, James, Chen, Lingyan, Mifsud, Borbala, Yao, Chen, Kraja, Aldi T, Cartwright, James H, Hellwege, Jacklyn N, Giri, Ayush, Tragante, Vinicius, Thorleifsson, Gudmar, Liu, Dajiang J, Prins, Bram P, Stewart, Isobel D, Cabrera, Claudia P, Eales, James M, Akbarov, Artur, Auer, Paul L, Bielak, Lawrence F, Bis, Joshua C, Braithwaite, Vickie S, Brody, Jennifer A, Daw, E Warwick, Warren, Helen R, Drenos, Fotios, Nielsen, Sune Fallgaard, Faul, Jessica D, Fauman, Eric B, Fava, Cristiano, Ferreira, Teresa, Foley, Christopher N, Franceschini, Nora, Gao, He, Giannakopoulou, Olga, Giulianini, Franco, Gudbjartsson, Daniel F, Guo, Xiuqing, Harris, Sarah E, Havulinna, Aki S, Helgadottir, Anna, Huffman, Jennifer E, Hwang, Shih-Jen, Kanoni, Stavroula, Kontto, Jukka, Larson, Martin G, Li-Gao, Ruifang, Lindström, Jaana, Lotta, Luca A, Lu, Yingchang, Luan, Jian'an, Mahajan, Anubha, Malerba, Giovanni, Masca, Nicholas G D, Mei, Hao, Menni, Cristina, Mook-Kanamori, Dennis O, Mosen-Ansorena, David, Müller-Nurasyid, Martina, Paré, Guillaume, Paul, Dirk S, Perola, Markus, Poveda, Alaitz, Rauramaa, Rainer, Richard, Melissa, Richardson, Tom G, Sepúlveda, Nuno, Sim, Xueling, Smith, Albert V, Smith, Jennifer A, Staley, James R, Stanáková, Alena, Sulem, Patrick, Thériault, Sébastien, Thorsteinsdottir, Unnur, Trompet, Stella, Varga, Tibor V, Velez Edwards, Digna R, Veronesi, Giovanni, Weiss, Stefan, Willems, Sara M, Yao, Jie, Young, Robin, Yu, Bing, Zhang, Weihua, Zhao, Jing-Hua, Zhao, Wei, Evangelou, Evangelos, Aeschbacher, Stefanie, Asllanaj, Eralda, Blankenberg, Stefan, Bonnycastle, Lori L, Bork-Jensen, Jette, Brandslund, Ivan, Braund, Peter S, Burgess, Stephen, Cho, Kelly, Christensen, Cramer, Connell, John, Mutsert, Renée de, Dominiczak, Anna F, Dörr, Marcus, Eiriksdottir, Gudny, Farmaki, Aliki-Eleni, Gaziano, J Michael, Grarup, Niels, Grove, Megan L, Hallmans, Göran, Hansen, Torben, Have, Christian T, Heiss, Gerardo, Jørgensen, Marit E, Jousilahti, Pekka, Kajantie, Eero, Kamat, Mihir, Käräjämäki, AnneMari, Karpe, Fredrik, Koistinen, Heikki A, Kovesdy, Csaba P, Kuulasmaa, Kari, Laatikainen, Tiina, Lannfelt, Lars, Lee, I-Te, Lee, Wen-Jane, Linneberg, Allan, Martin, Lisa W, Moitry, Marie, Nadkarni, Girish, Neville, Matt J, Palmer, Colin N A, Papanicolaou, George J, Pedersen, Oluf, Peters, James, Poulter, Neil, Rasheed, Asif, Rasmussen, Katrine L, Rayner, N William, Mägi, Reedik, Renström, Frida, Rettig, Rainer, Rossouw, Jacques, Schreiner, Pamela J, Sever, Peter S, Sigurdsson, Emil L, Skaaby, Tea, Sun, Yan V, Sundström, Johan, Thorgeirsson, Gudmundur, Esko, Tõnu, Trabetti, Elisabetta, Tsao, Philip S, Tuomi, Tiinamaija, Turner, Stephen T, Tzoulaki, Ioanna, Vaartjes, Ilonca, Vergnaud, Anne-Claire, Willer, Cristen J, Wilson, Peter W F, Witte, Daniel R, Yonova-Doing, Ekaterina, Zhang, He, Aliya, Naheed, Almgren, Peter, Amouyel, Philippe, Asselbergs, Folkert W, Barnes, Michael R, Blakemore, Alexandra I, Boehnke, Michael, Bots, Michiel L, Bottinger, Erwin P, Buring, Julie E, Chambers, John C, Chen, Yii-Der Ida, Chowdhury, Rajiv, Conen, David, Correa, Adolfo, Davey Smith, George, Boer, Rudolf A de, Deary, Ian J, Dedoussis, George, Deloukas, Panos, Di Angelantonio, Emanuele, Elliott, Paul, Felix, Stephan B, Ferrières, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W, Franks, Stephen, Frossard, Philippe, Gambaro, Giovanni, Gaunt, Tom R, Groop, Leif, Gudnason, Vilmundur, Harris, Tamara B, Hayward, Caroline, Hennig, Branwen J, Herzig, Karl-Heinz, Ingelsson, Erik, Tuomilehto, Jaakko, Järvelin, Marjo-Riitta, Jukema, J Wouter, Kardia, Sharon L R, Kee, Frank, Kooner, Jaspal S, Kooperberg, Charles, Launer, Lenore J, Lind, Lars, Loos, Ruth J F, Majumder, Abdulla Al Shafi, Laakso, Markku, McCarthy, Mark I, Melander, Olle, Mohlke, Karen L, Murray, Alison D, Nordestgaard, Børge Grønne, Orho-Melander, Marju, Packard, Chris J, Padmanabhan, Sandosh, Palmas, Walter, Polasek, Ozren, Porteous, David J, Prentice, Andrew M, Province, Michael A, Relton, Caroline L, Rice, Kenneth, Ridker, Paul M, Rolandsson, Olov, Rosendaal, Frits R, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J, Sattar, Naveed, Sheu, Wayne H-H, Smith, Blair H, Soranzo, Nicole, Spector, Timothy D, Starr, John M, Sebert, Sylvain, Taylor, Kent D, Lakka, Timo A, Timpson, Nicholas J, Tobin, Martin D, van der Harst, Pim, van der Meer, Peter, Ramachandran, Vasan S, Verweij, Niek, Virtamo, Jarmo, Völker, Uwe, Weir, David R, Zeggini, Eleftheria, Charchar, Fadi J, Wareham, Nicholas J, Langenberg, Claudia, Tomaszewski, Maciej, Butterworth, Adam S, Caulfield, Mark J, Danesh, John, Edwards, Todd L, Holm, Hilma, Hung, Adriana M, Lindgren, Cecilia M, Liu, Chunyu, Manning, Alisa K, Morris, Andrew P, Morrison, Alanna C, O'Donnell, Christopher J, Psaty, Bruce M, Saleheen, Danish, Stefansson, Kari, Boerwinkle, Eric, Chasman, Daniel I, Levy, Daniel, Newton-Cheh, Christopher, Munroe, Patricia B, and Howson, Joanna M M

Abstract

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.

Published
2020
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45. Neurology-related protein biomarkers are associated with general fluid cognitive ability and brain volume in older age

Author

Harris, Sarah E., primary, Cox, Simon R., additional, Bell, Steven, additional, Marioni, Riccardo E., additional, Prins, Bram P, additional, Pattie, Alison, additional, Corley, Janie, additional, Muñoz Maniega, Susana, additional, Valdés Hernández, Maria, additional, Morris, Zoe, additional, John, Sally, additional, Bronson, Paola G., additional, Tucker-Drob, Elliot M., additional, Starr, John M., additional, Bastin, Mark E., additional, Wardlaw, Joanna M., additional, Butterworth, Adam S, additional, and Deary, Ian J., additional

Published
2019
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46. Genetic Landscape of the ACE2 Coronavirus Receptor

Author

Yang, Zhijian, Macdonald-Dunlop, Erin, Chen, Jiantao, Zhai, Ranran, Li, Ting, Richmond, Anne, Klarić, Lucija, Pirastu, Nicola, Ning, Zheng, Zheng, Chenqing, Wang, Yipeng, Huang, Tingting, He, Yazhou, Guo, Huiming, Ying, Kejun, Gustafsson, Stefan, Prins, Bram, Ramisch, Anna, Dermitzakis, Emmanouil T., Png, Grace, Eriksson, Niclas, Haessler, Jeffrey, Hu, Xiaowei, Zanetti, Daniela, Boutin, Thibaud, Hwang, Shih-Jen, Wheeler, Eleanor, Pietzner, Maik, Raffield, Laura M., Kalnapenkis, Anette, Peters, James E., Viñuela, Ana, Gilly, Arthur, Elmståhl, Sölve, Dedoussis, George, Petrie, John R., Polašek, Ozren, Folkersen, Lasse, Chen, Yan, Yao, Chen, Võsa, Urmo, Pairo-Castineira, Erola, Clohisey, Sara, Bretherick, Andrew D., Rawlik, Konrad, Esko, Tõnu, Enroth, Stefan, Johansson, Åsa, Gyllensten, Ulf, Langenberg, Claudia, Levy, Daniel, Hayward, Caroline, Assimes, Themistocles L., Kooperberg, Charles, Manichaikul, Ani W., Siegbahn, Agneta, Wallentin, Lars, Lind, Lars, Zeggini, Eleftheria, Schwenk, Jochen M., Butterworth, Adam S., Michaëlsson, Karl, Pawitan, Yudi, Joshi, Peter K., Baillie, J. Kenneth, Mälarstig, Anders, Reiner, Alexander P., Wilson, James F., and Shen, Xia

Published
2022
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47. Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

Author

Wain, Louise V., Shrine, Nick, Erzurumluoglu, A. Mesut, Noyvert, Boris, Bossini-Castillo, Lara, Henry, Amanda P., Portelli, Michael A., Hall, Robert J., Billington, Charlotte K., Rimington, Tracy L., Fenech, Anthony G., Johnson, Catherine, Blake, Tineka, Jackson, Victoria E., Allen, Richard J., Prins, Bram P., Campbell, Archie, Sayers, Ian, and Hall, Ian P.

Subjects
Genetics research, Genome-wide association studies, Respiratory tract diseases, respiratory tract diseases
Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20–1.27), P = 5.05 × 10−49), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.

Published
2017

48. Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval

Author

Lin, Honghuang, primary, van Setten, Jessica, additional, Smith, Albert V., additional, Bihlmeyer, Nathan A., additional, Warren, Helen R., additional, Brody, Jennifer A., additional, Radmanesh, Farid, additional, Hall, Leanne, additional, Grarup, Niels, additional, Müller-Nurasyid, Martina, additional, Boutin, Thibaud, additional, Verweij, Niek, additional, Lin, Henry J., additional, Li-Gao, Ruifang, additional, van den Berg, Marten E., additional, Marten, Jonathan, additional, Weiss, Stefan, additional, Prins, Bram P., additional, Haessler, Jeffrey, additional, Lyytikäinen, Leo-Pekka, additional, Mei, Hao, additional, Harris, Tamara B., additional, Launer, Lenore J., additional, Li, Man, additional, Alonso, Alvaro, additional, Soliman, Elsayed Z., additional, Connell, John M., additional, Huang, Paul L., additional, Weng, Lu-Chen, additional, Jameson, Heather S., additional, Hucker, William, additional, Hanley, Alan, additional, Tucker, Nathan R., additional, Chen, Yii-Der Ida, additional, Bis, Joshua C., additional, Rice, Kenneth M., additional, Sitlani, Colleen M., additional, Kors, Jan A., additional, Xie, Zhijun, additional, Wen, Chengping, additional, Magnani, Jared W., additional, Nelson, Christopher P., additional, Kanters, Jørgen K., additional, Sinner, Moritz F., additional, Strauch, Konstantin, additional, Peters, Annette, additional, Waldenberger, Melanie, additional, Meitinger, Thomas, additional, Bork-Jensen, Jette, additional, Pedersen, Oluf, additional, Linneberg, Allan, additional, Rudan, Igor, additional, de Boer, Rudolf A., additional, van der Meer, Peter, additional, Yao, Jie, additional, Guo, Xiuqing, additional, Taylor, Kent D., additional, Sotoodehnia, Nona, additional, Rotter, Jerome I., additional, Mook-Kanamori, Dennis O., additional, Trompet, Stella, additional, Rivadeneira, Fernando, additional, Uitterlinden, André, additional, Eijgelsheim, Mark, additional, Padmanabhan, Sandosh, additional, Smith, Blair H., additional, Völzke, Henry, additional, Felix, Stephan B., additional, Homuth, Georg, additional, Völker, Uwe, additional, Mangino, Massimo, additional, Spector, Timothy D., additional, Bots, Michiel L., additional, Perez, Marco, additional, Kähönen, Mika, additional, Raitakari, Olli T., additional, Gudnason, Vilmundur, additional, Arking, Dan E., additional, Munroe, Patricia B., additional, Psaty, Bruce M., additional, van Duijn, Cornelia M., additional, Benjamin, Emelia J., additional, Rosand, Jonathan, additional, Samani, Nilesh J., additional, Hansen, Torben, additional, Kääb, Stefan, additional, Polasek, Ozren, additional, van der Harst, Pim, additional, Heckbert, Susan R., additional, Jukema, J. Wouter, additional, Stricker, Bruno H., additional, Hayward, Caroline, additional, Dörr, Marcus, additional, Jamshidi, Yalda, additional, Asselbergs, Folkert W., additional, Kooperberg, Charles, additional, Lehtimäki, Terho, additional, Wilson, James G., additional, Ellinor, Patrick T., additional, Lubitz, Steven A., additional, and Isaacs, Aaron, additional

Published
2018
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49. Blood Eosinophil Count and Metabolic, Cardiac and Pulmonary Outcomes: A Mendelian Randomization Study

Author

Amini, Marzyeh, primary, Vonk, Judith M., additional, Abbasi, Ali, additional, Prins, Bram P., additional, Bruinenberg, Marcel, additional, Franke, Lude, additional, van der Harst, Pim, additional, Navis, Gerjan, additional, Koppelman, Gerard H., additional, Wolffenbuttel, Bruce H. R., additional, Boezen, H. Marike, additional, Snieder, Harold, additional, Chasman, Daniel I., additional, and Alizadeh, Behrooz Z., additional

Published
2018
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50. Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval

Author

Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, Isaacs, Aaron, Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, and Isaacs, Aaron

Published
2018

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