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201. Older biological age is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank

Author: Wang, Qingning, primary, Codd, Veryan, additional, Raisi-Estabragh, Zahra, additional, Musicha, Crispin, additional, Bountziouka, Vasiliki, additional, Kaptoge, Stephen, additional, Allara, Elias, additional, Angelantonio, Emanuele Di, additional, Butterworth, Adam S., additional, Wood, Angela M., additional, Thompson, John R., additional, Petersen, Steffen E, additional, Harvey, Nicholas C., additional, Danesh, John N., additional, Samani, Nilesh J., additional, and Nelson, Christopher P., additional
Published: 2021
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202. Plasma vitamin C and type 2 diabetes

Author: Zheng, Ju-Sheng, Luan, Jian'an, Sofianopoulou, Eleni, Imamura, Fumiaki, Stewart, Isobel D., Day, Felix R., Pietzner, Maik, Wheeler, Eleanor, Lotta, Luca A., Gundersen, Thomas E., Amiano, Pilar, Ardanaz, Eva, Chirlaque, Maria-Dolores, Fagherazzi, Guy, Franks, Paul W., Kaaks, Rudolf, Laouali, Nasser, Mancini, Francesca Romana, Nilsson, Peter M., Onland-Moret, N. Charlotte, Olsen, Anja, Overvad, Kim, Panico, Salvatore, Palli, Domenico, Ricceri, Fulvio, Rolandsson, Olov, Spijkerman, Annemieke M. W., Sanchez, Maria-Jose, Schulze, Matthias B. (Prof. Dr.), Sala, Nuria, Sieri, Sabina, Tjonneland, Anne, Tumino, Rosario, van der Schouw, Yvonne T., Weiderpass, Elisabete, Riboli, Elio, Danesh, John, Butterworth, Adam S., Sharp, Stephen J., Langenberg, Claudia, Forouhi, Nita G., and Wareham, Nicholas J.
Subjects: ddc:540, Institut für Ernährungswissenschaft
Abstract: OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 x 10(-8)), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
Published: 2020

203. The Polygenic and Monogenic Basis of Blood Traits and Diseases

Author: Vuckovic, Dragana, Bao, Erik L, Akbari, Parsa, Lareau, Caleb A, Mousas, Abdou, Jiang, Tao, Chen, Ming-Huei, Raffield, Laura M, Tardaguila, Manuel, Huffman, Jennifer E, Ritchie, Scott C, Megy, Karyn, Ponstingl, Hannes, Penkett, Christopher J, Albers, Patrick K, Wigdor, Emilie M, Sakaue, Saori, Moscati, Arden, Manansala, Regina, Lo, Ken Sin, Qian, Huijun, Akiyama, Masato, Bartz, Traci M, Ben-Shlomo, Yoav, Beswick, Andrew, Bork-Jensen, Jette, Bottinger, Erwin P, Brody, Jennifer A, Van Rooij, Frank JA, Chitrala, Kumaraswamy N, Wilson, Peter WF, Choquet, Hélène, Danesh, John, Di Angelantonio, Emanuele, Dimou, Niki, Ding, Jingzhong, Elliott, Paul, Esko, Tõnu, Evans, Michele K, Felix, Stephan B, Floyd, James S, Broer, Linda, Grarup, Niels, Guo, Michael H, Guo, Qi, Greinacher, Andreas, Haessler, Jeff, Hansen, Torben, Howson, Joanna MM, Huang, Wei, Jorgenson, Eric, Kacprowski, Tim, Kähönen, Mika, Kamatani, Yoichiro, Kanai, Masahiro, Karthikeyan, Savita, Koskeridis, Fotios, Lange, Leslie A, Lehtimäki, Terho, Linneberg, Allan, Liu, Yongmei, Lyytikäinen, Leo-Pekka, Manichaikul, Ani, Matsuda, Koichi, Mohlke, Karen L, Mononen, Nina, Murakami, Yoshinori, Nadkarni, Girish N, Nikus, Kjell, Pankratz, Nathan, Pedersen, Oluf, Preuss, Michael, Psaty, Bruce M, Raitakari, Olli T, Rich, Stephen S, Rodriguez, Benjamin AT, Rosen, Jonathan D, Rotter, Jerome I, Schubert, Petra, Spracklen, Cassandra N, Surendran, Praveen, Tang, Hua, Tardif, Jean-Claude, Ghanbari, Mohsen, Völker, Uwe, Völzke, Henry, Watkins, Nicholas A, Weiss, Stefan, VA Million Veteran Program, Cai, Na, Kundu, Kousik, Watt, Stephen B, Walter, Klaudia, Zonderman, Alan B, Cho, Kelly, Li, Yun, Loos, Ruth JF, Knight, Julian C, Georges, Michel, Stegle, Oliver, Evangelou, Evangelos, Okada, Yukinori, Roberts, David J, Inouye, Michael, Johnson, Andrew D, Auer, Paul L, Astle, William J, Reiner, Alexander P, Butterworth, Adam S, Ouwehand, Willem H, Lettre, Guillaume, Sankaran, Vijay G, Soranzo, Nicole, Ritchie, Scott [0000-0002-8454-9548], Megy, Karyn [0000-0002-2826-3879], Danesh, John [0000-0003-1158-6791], Di Angelantonio, Emanuele [0000-0001-8776-6719], Kundu, Kousik [0000-0002-1019-8351], Inouye, Michael [0000-0001-9413-6520], Astle, William [0000-0001-8866-6672], Butterworth, Adam [0000-0002-6915-9015], Ouwehand, Willem [0000-0002-7744-1790], Soranzo, Nicole [0000-0003-1095-3852], and Apollo - University of Cambridge Repository
Subjects: Male, UK Biobank, Multifactorial Inheritance, polygenic risk, rare disease, Polymorphism, Single Nucleotide, hematopoiesis, splicing, Phenotype, fine-mapping, blood, chromatin, Humans, genetics, Female, Gene Regulatory Networks, Genetic Predisposition to Disease, omnigenic, Genome-Wide Association Study
Abstract: Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
Published: 2020
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204. Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

Author: Chen, Ming-Huei, Raffield, Laura M, Mousas, Abdou, Sakaue, Saori, Huffman, Jennifer E, Moscati, Arden, Trivedi, Bhavi, Jiang, Tao, Akbari, Parsa, Vuckovic, Dragana, Bao, Erik L, Zhong, Xue, Manansala, Regina, Laplante, Véronique, Chen, Minhui, Lo, Ken Sin, Qian, Huijun, Lareau, Caleb A, Beaudoin, Mélissa, Hunt, Karen A, Akiyama, Masato, Bartz, Traci M, Ben-Shlomo, Yoav, Beswick, Andrew, Bork-Jensen, Jette, Bottinger, Erwin P, Brody, Jennifer A, van Rooij, Frank JA, Chitrala, Kumaraswamynaidu, Cho, Kelly, Choquet, Hélène, Correa, Adolfo, Danesh, John, Di Angelantonio, Emanuele, Dimou, Niki, Ding, Jingzhong, Elliott, Paul, Esko, Tõnu, Evans, Michele K, Floyd, James S, Broer, Linda, Grarup, Niels, Guo, Michael H, Greinacher, Andreas, Haessler, Jeff, Hansen, Torben, Howson, Joanna MM, Huang, Qin Qin, Huang, Wei, Jorgenson, Eric, Kacprowski, Tim, Kähönen, Mika, Kamatani, Yoichiro, Kanai, Masahiro, Karthikeyan, Savita, Koskeridis, Fotis, Lange, Leslie A, Lehtimäki, Terho, Lerch, Markus M, Linneberg, Allan, Liu, Yongmei, Lyytikäinen, Leo-Pekka, Manichaikul, Ani, Martin, Hilary C, Matsuda, Koichi, Mohlke, Karen L, Mononen, Nina, Murakami, Yoshinori, Nadkarni, Girish N, Nauck, Matthias, Nikus, Kjell, Ouwehand, Willem H, Pankratz, Nathan, Pedersen, Oluf, Preuss, Michael, Psaty, Bruce M, Raitakari, Olli T, Roberts, David J, Rich, Stephen S, Rodriguez, Benjamin AT, Rosen, Jonathan D, Rotter, Jerome I, Schubert, Petra, Spracklen, Cassandra N, Surendran, Praveen, Tang, Hua, Tardif, Jean-Claude, Trembath, Richard C, Ghanbari, Mohsen, Völker, Uwe, Völzke, Henry, Watkins, Nicholas A, Zonderman, Alan B, VA Million Veteran Program, Wilson, Peter WF, Li, Yun, Butterworth, Adam S, Gauchat, Jean-François, Chiang, Charleston WK, and Li, Bingshan
Subjects: interleukin-7, Single Nucleotide, Biological Sciences, phenome-wide association study, genetic architecture, Medical and Health Sciences, White People, Phenotype, HEK293 Cells, selective sweeps, Good Health and Well Being, Asian People, fine-mapping, polygenic trait score, VA Million Veteran Program, Mutation, Genetics, Humans, Missense, Polymorphism, Genome-Wide Association Study, Developmental Biology
Abstract: Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p< 5× 10-9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count invivo and IL-7 secretion levels invitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.
Published: 2020

205. Development and validation of a universal blood donor genotyping platform: a multinational prospective study

Author: Gleadall, Nicholas S, Veldhuisen, Barbera, Gollub, Jeremy, Butterworth, Adam S, Ord, John, Penkett, Christopher J, Timmer, Tiffany C, Sauer, Carolin M, Van Der Bolt, Nieke, Brown, Colin, Brugger, Kim, Dilthey, Alexander T, Duarte, Daniel, Grimsley, Shane, Van Den Hurk, Katja, Jongerius, John M, Luken, Jessie, Megy, Karyn, Miflin, Gail, Nelson, Christopher S, Prinsze, Femmeke J, Sambrook, Jennifer, Simeoni, Ilenia, Sweeting, Michael, Thornton, Nicole, Trompeter, Sara, Tuna, Salih, Varma, Ram, Walker, Matthew R, NIHR BioResource, Danesh, John, Roberts, David J, Ouwehand, Willem H, Stirrups, Kathleen E, Rendon, Augusto, Westhoff, Connie M, Di Angelantonio, Emanuele, Van Der Schoot, C Ellen, Astle, William J, Watkins, Nicholas A, Lane, William J, Butterworth, Adam [0000-0002-6915-9015], Sauer, Carolin [0000-0003-2168-6630], Megy, Karyn [0000-0002-2826-3879], Danesh, John [0000-0003-1158-6791], Ouwehand, Willem [0000-0002-7744-1790], Johnson, Kathleen [0000-0002-6823-3252], Rendon Restrepo, Augusto [0000-0001-8994-0039], Di Angelantonio, Emanuele [0000-0001-8776-6719], Astle, William [0000-0001-8866-6672], and Apollo - University of Cambridge Repository
Subjects: Genotype, Isoantibodies, Humans, Blood Donors, Blood Transfusion, Prospective Studies
Abstract: Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non-self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates. This DNA-based test is capable of simultaneously typing most clinically relevant red blood cell (RBC), human platelet (HPA), and human leukocyte (HLA) antigens. Validation was performed, using samples from 7927 European, 27 South Asian, 21 East Asian, and 9 African blood donors enrolled in 2 national biobanks. We illustrated the usefulness of the platform by analyzing antibody data from patients sensitized with multiple RBC alloantibodies. Genotyping results demonstrated concordance of 99.91%, 99.97%, and 99.03% with RBC, HPA, and HLA clinically validated typing results in 89 371, 3016, and 9289 comparisons, respectively. Genotyping increased the total number of antigen typing results available from 110 980 to >1 200 000. Dense donor typing allowed identification of 2 to 6 times more compatible donors to serve 3146 patients with multiple RBC alloantibodies, providing at least 1 match for 176 individuals for whom previously no blood could be found among the same donors. This genotyping technology is already being used to type thousands of donors taking part in national genotyping studies. Extraction of dense antigen-typing data from these cohorts provides blood supply organizations with the opportunity to implement a policy of genomics-based precision matching of blood.
Published: 2020

206. Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians

Author: Wang, Minxian, Menon, Ramesh, Mishra, Sanghamitra, Patel, Aniruddh P, Chaffin, Mark, Tanneeru, Deepak, Deshmukh, Manjari, Mathew, Oshin, Apte, Sanika, Devanboo, Christina S, Sundaram, Sumathi, Lakshmipathy, Praveena, Murugan, Sakthivel, Sharma, Krishna Kumar, Rajendran, Karthikeyan, Santhosh, Sam, Thachathodiyl, Rajesh, Ahamed, Hisham, Balegadde, Aniketh Vijay, Alexander, Thomas, Swaminathan, Krishnan, Gupta, Rajeev, Mullasari, Ajit S, Sigamani, Alben, Kanchi, Muralidhar, Peterson, Andrew S, Butterworth, Adam S, Danesh, John, Di Angelantonio, Emanuele, Naheed, Aliya, Inouye, Michael, Chowdhury, Rajiv, Vedam, Ramprasad L, Kathiresan, Sekar, Gupta, Ravi, and Khera, Amit V
Subjects: Adult, Male, Bangladesh, Multifactorial Inheritance, India, Coronary Artery Disease, Middle Aged, genomic medicine, Case-Control Studies, South Asian, Humans, polygenic score, Female, Aged, Genome-Wide Association Study
Abstract: BACKGROUND: Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population. OBJECTIVES: This analysis used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians. METHODS: This GPSCAD was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPSCAD reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India. RESULTS: The GPSCAD, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p < 0.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p < 0.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPSCAD distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p < 0.05 for each). CONCLUSIONS: The new GPSCAD has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.
Published: 2020
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207. 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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208. Rare and low-frequency coding variants alter human adult height

Author: Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R., Kjaer, Troels R., Fine, Rebecca S., Lu, Yingchang, Schurmann, Claudia, Highland, Heather M., Reger, Sina, Thorleifsson, Gudmar, Justice, Anne E., Lamparter, David, Stirrups, Kathleen E., Turcot, Valrie, Young, Kristin L., Winkler, Thomas W., Esko, Tnu, Karaderi, Tugce, Locke, Adam E., Masca, Nicholas G. D., Ng, Maggie C. Y., Mudgal, Poorva, Rivas, Manuel A., Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K., Adair, Linda S., Alam, Dewan S., Albrecht, Eva, Allin, Kristine H., Allison, Matthew, Amouyel, Philippe, Appel, Emil V., Arveiler, Dominique, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Banas, Bernhard, Bang, Lia E., Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Bger, Carsten A., Bonnycastle, Lori L., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Burt, Amber A., Butterworth, Adam S., Carey, David J., Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul I. W., de Borst, Gert J., de Denus, Simon, de Groot, Mark C. H., de Mutsert, Rene, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., den Hollander, Anneke I., Dennis, Joe G., Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M., Easton, Douglas F., Ebeling, Tapani, Edwards, Todd L., Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D., Feitosa, Mary F., Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M., Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franks, Paul W., Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D., Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Hayward, Caroline, He, Liang, Heid, Iris M., Heikkil, Kauko, Helgeland, yvind, Hernesniemi, Jussi, Hewitt, Alex W., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hoyng, Carel B., Huang, Paul L., Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Hkan, Jarvik, Gail P., Jensen, Gorm B., Jhun, Min A., Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jrgensen, Marit E., Jrgensen, Torben, Jousilahti, Pekka, Jukema, J. Wouter, Kahali, Bratati, Kahn, Ren S., Khnen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A., Kitajima, Hidetoshi, Kluivers, Kirsten B., Kocher, Thomas, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Kry, Sbastien, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lakka, Timo A., Lange, Ethan M., Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Larson, Eric B., Lee, I-Te, Lehtimki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrm, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jianan, Lubitz, Steven A., Lyytikinen, Leo-Pekka, Mackey, David A., Madden, Pamela A. F., Manning, Alisa K., Mnnist, Satu, Marenne, Galle, Marten, Jonathan, Martin, Nicholas G., Mazul, Angela L., Meidtner, Karina, Metspalu, Andres, Mitchell, Paul, Mohlke, Karen L., Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew D., Morris, Andrew P., Mller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njlstad, Pl R., Nordestgaard, Brge G., Ntalla, Ioanna, OConnel, Jeffrey R., Oksa, Heikki, Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Person, Thomas N., Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renstrm, Frida, Ridker, Paul M., Rioux, John D., Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert Vernon, Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Steinthorsdottir, Valgerdur, Stringham, Heather M., Stumvoll, Michael, Surendran, Praveen, t Hart, Leen M., Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorsteinsdottir, Unnur, Thuesen, Betina H., Tnjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andr G., Ulivi, Sheila, van der Laan, Sander W., Van Der Leij, Andries R., van Duijn, Cornelia M., van Schoor, Natasja M., van Setten, Jessica, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J., Warren, Helen R., Wessel, Jennifer, Willems, Sara M., Wilson, James G., Witte, Daniel R., Woods, Michael O., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I, Boehnke, Michael, Kathiresan, Sekar, McCarthy, Mark I., Willer, Cristen J., Stefansson, Kari, Borecki, Ingrid B., Liu, Dajiang J., North, Kari E., Heard-Costa, Nancy L., Pers, Tune H., Lindgren, Cecilia M., Oxvig, Claus, Kutalik, Zoltn, Rivadeneira, Fernando, Loos, Ruth J. F., Frayling, Timothy M., Hirschhorn, Joel N., Deloukas, Panos, and Lettre, Guillaume
Subjects: Body height -- Genetic aspects, Genetic variation -- Observations, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.14.8%) and effects of up to 2centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 12centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways., Author(s): Eirini Marouli [1]; Mariaelisa Graff [2]; Carolina Medina-Gomez [3, 4]; Ken Sin Lo [5]; Andrew R. Wood [6]; Troels R. Kjaer [7]; Rebecca S. Fine [8, 9, 10]; Yingchang [...]
Published: 2017
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209. Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals

Author: Folkersen, Lasse, Gustafsson, Stefan, Wang, Qin, Hvidberg Hansen, Daniel, 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, Michaëlsson, 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, Mälarstig, Anders, Folkersen, Lasse, Gustafsson, Stefan, Wang, Qin, Hvidberg Hansen, Daniel, 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, Michaëlsson, 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
Abstract: Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health., De tre första författarna delar förstaförfattarskapetDe tre sista författarna delar sistaförfattarskapet
Published: 2020
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210. ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels : a Mendelian randomization study

Author: Gill, Dipender, Arvanitis, Marios, Carter, Paul, Cordero, Ana I. Hernandez, Jo, Brian, Karhunen, Ville, Larsson, Susanna C., Li, Xuan, Lockhart, Sam M., Mason, Amy, Pashos, Evanthia, Saha, Ashis, Tan, Vanessa Y., Zuber, Verena, Bosse, Yohan, Fahle, Sarah, Hao, Ke, Jiang, Tao, Joubert, Philippe, Lunt, Alan C., Ouwehand, Willem Hendrik, Roberts, David J., Timens, Wim, van den Berge, Maarten, Watkins, Nicholas A., Battle, Alexis, Butterworth, Adam S., Danesh, John, Di Angelantonio, Emanuele, Engelhardt, Barbara E., Peters, James E., Sin, Don D., Burgess, Stephen, Gill, Dipender, Arvanitis, Marios, Carter, Paul, Cordero, Ana I. Hernandez, Jo, Brian, Karhunen, Ville, Larsson, Susanna C., Li, Xuan, Lockhart, Sam M., Mason, Amy, Pashos, Evanthia, Saha, Ashis, Tan, Vanessa Y., Zuber, Verena, Bosse, Yohan, Fahle, Sarah, Hao, Ke, Jiang, Tao, Joubert, Philippe, Lunt, Alan C., Ouwehand, Willem Hendrik, Roberts, David J., Timens, Wim, van den Berge, Maarten, Watkins, Nicholas A., Battle, Alexis, Butterworth, Adam S., Danesh, John, Di Angelantonio, Emanuele, Engelhardt, Barbara E., Peters, James E., Sin, Don D., and Burgess, Stephen
Abstract: Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 x 10(-4)) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.
Published: 2020
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211. 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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212. Lipoprotein(a) in Alzheimer, Atherosclerotic, Cerebrovascular, Thrombotic, and Valvular Disease Mendelian Randomization Investigation

Author: Larsson, Susanna C., Gill, Dipender, Mason, Amy M., Jiang, Tao, Back, Magnus, Butterworth, Adam S., Burgess, Stephen, Larsson, Susanna C., Gill, Dipender, Mason, Amy M., Jiang, Tao, Back, Magnus, Butterworth, Adam S., and Burgess, Stephen
Published: 2020
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213. Glycemic index, glycemic load, and risk of coronary heart disease : a pan-European cohort study

Author: Sieri, Sabina, Agnoli, Claudia, Grioni, Sara, Weiderpass, Elisabete, Mattiello, Amalia, Sluijs, Ivonne, Sanchez, Maria Jose, Jakobsen, Marianne Uhre, Sweeting, Michael, van der Schouw, Yvonne T., Nilsson, Lena Maria, Wennberg, Patrik, Katzke, Verena A., Kuhn, Tilman, Overvad, Kim, Tong, Tammy Y. N., Conchi, Moreno-Iribas, Ramon Quiros, Jose, Manuel Garcia-Torrecillas, Juan, Mokoroa, Olatz, Gomez, Jesus-Humberto, Tjonneland, Anne, Sonestedt, Emiliy, Trichopoulou, Antonia, Karakatsani, Anna, Valanou, Elissavet, Boer, Jolanda M. A., Verschuren, W. M. Monique, Boutron-Ruault, Marie-Christine, Fagherazzi, Guy, Madika, Anne-Laure, Bergmann, Manuela M., Schulze, Matthias B., Ferrari, Pietro, Freisling, Heinz, Lennon, Hannah, Sacerdote, Carlotta, Masala, Giovanna, Tumino, Rosario, Riboli, Elio, Wareham, Nicholas J., Danesh, John, Forouhi, Nita G., Butterworth, Adam S., Krogh, Vittorio, Sieri, Sabina, Agnoli, Claudia, Grioni, Sara, Weiderpass, Elisabete, Mattiello, Amalia, Sluijs, Ivonne, Sanchez, Maria Jose, Jakobsen, Marianne Uhre, Sweeting, Michael, van der Schouw, Yvonne T., Nilsson, Lena Maria, Wennberg, Patrik, Katzke, Verena A., Kuhn, Tilman, Overvad, Kim, Tong, Tammy Y. N., Conchi, Moreno-Iribas, Ramon Quiros, Jose, Manuel Garcia-Torrecillas, Juan, Mokoroa, Olatz, Gomez, Jesus-Humberto, Tjonneland, Anne, Sonestedt, Emiliy, Trichopoulou, Antonia, Karakatsani, Anna, Valanou, Elissavet, Boer, Jolanda M. A., Verschuren, W. M. Monique, Boutron-Ruault, Marie-Christine, Fagherazzi, Guy, Madika, Anne-Laure, Bergmann, Manuela M., Schulze, Matthias B., Ferrari, Pietro, Freisling, Heinz, Lennon, Hannah, Sacerdote, Carlotta, Masala, Giovanna, Tumino, Rosario, Riboli, Elio, Wareham, Nicholas J., Danesh, John, Forouhi, Nita G., Butterworth, Adam S., and Krogh, Vittorio
Abstract: Background: High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. Objectives: The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes. Methods: This large prospective study-the European Prospective Investigation into Cancer and Nutrition-consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models. Results: After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m(2)) >= 25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI <25 [HR: 1.09 (95% CI: 0.98, 1.22) per 50 g/d) (P-interaction = 0.022). The GL-CHD association did not differ between men [HR: 1.19 (95% CI: 1.08, 1.30) per 50 g/d] and women [HR: 1.22 (95% CI: 1.07, 1.40) per 50 g/d] (test for interaction not significant). GI was associated with CHD risk only in the continuous model [HR: 1.04 (95% CI: 1.00, 1.08) per 5 units/d]. High available carbohydrate was associated with greater CHD risk [HR: 1.11 (95% CI: 1.03, 1.18) per 50 g/d]. High sugar intake was associated with greater CHD risk [HR: 1.09 (95% CI: 1.02, 1.17) per 50 g/d]. Conclusions: This large pan-European study provides robust additional support for the hypothesis that a diet that induces a high glucose response is associated with greater CHD risk.
Published: 2020
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214. The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke : a prospective study of 418 329 participants in the EPIC cohort across nine European countries

Author: Tong, Tammy Y. N., Appleby, Paul N., Key, Timothy J., Dahm, Christina C., Overvad, Kim, Olsen, Anja, Tjonneland, Anne, Katzke, Verena, Kuhn, Tilman, Boeing, Heiner, Karakatsani, Anna, Peppa, Eleni, Trichopoulou, Antonia, Weiderpass, Elisabete, Masala, Giovanna, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Boer, Jolanda M. A., Verschuren, W. M. Monique, Quiros, J. Ramon, Agudo, Antonio, Rodriguez-Barranco, Miguel, Imaz, Liher, Chirlaque, Maria-Dolores, Moreno-Iribas, Conchi, Engstrom, Gunnar, Sonestedt, Emily, Lind, Marcus, Otten, Julia, Khaw, Kay-Tee, Aune, Dagfinn, Riboli, Elio, Wareham, Nicholas J., Imamura, Fumiaki, Forouhi, Nita G., di Angelantonio, Emanuele, Wood, Angela M., Butterworth, Adam S., Perez-Cornago, Aurora, Tong, Tammy Y. N., Appleby, Paul N., Key, Timothy J., Dahm, Christina C., Overvad, Kim, Olsen, Anja, Tjonneland, Anne, Katzke, Verena, Kuhn, Tilman, Boeing, Heiner, Karakatsani, Anna, Peppa, Eleni, Trichopoulou, Antonia, Weiderpass, Elisabete, Masala, Giovanna, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Boer, Jolanda M. A., Verschuren, W. M. Monique, Quiros, J. Ramon, Agudo, Antonio, Rodriguez-Barranco, Miguel, Imaz, Liher, Chirlaque, Maria-Dolores, Moreno-Iribas, Conchi, Engstrom, Gunnar, Sonestedt, Emily, Lind, Marcus, Otten, Julia, Khaw, Kay-Tee, Aune, Dagfinn, Riboli, Elio, Wareham, Nicholas J., Imamura, Fumiaki, Forouhi, Nita G., di Angelantonio, Emanuele, Wood, Angela M., Butterworth, Adam S., and Perez-Cornago, Aurora
Abstract: Aim: To investigate the associations between major foods and dietary fibre with subtypes of stroke in a large prospective cohort. Methods and results: We analysed data on 418 329 men and women from nine European countries, with an average of 12.7 years of follow-up. Diet was assessed using validated country-specific questionnaires which asked about habitual intake over the past year, calibrated using 24-h recalls. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HRs) for ischaemic and haemorrhagic stroke associated with consumption of red and processed meat, poultry, fish, dairy foods, eggs, cereals, fruit and vegetables, legumes, nuts and seeds, and dietary fibre. For ischaemic stroke (4281 cases), lower risks were observed with higher consumption of fruit and vegetables combined (HR; 95% CI per 200 g/day higher intake, 0.87; 0.82–0.93, P-trend < 0.001), dietary fibre (per 10 g/day, 0.77; 0.69–0.86, P-trend < 0.001), milk (per 200 g/day, 0.95; 0.91–0.99, P-trend = 0.02), yogurt (per 100 g/day, 0.91; 0.85–0.97, P-trend = 0.004), and cheese (per 30 g/day, 0.88; 0.81–0.97, P-trend = 0.008), while higher risk was observed with higher red meat consumption which attenuated when adjusted for the other statistically significant foods (per 50 g/day, 1.07; 0.96–1.20, P-trend = 0.20). For haemorrhagic stroke (1430 cases), higher risk was associated with higher egg consumption (per 20 g/day, 1.25; 1.09–1.43, P-trend = 0.002). Conclusion: Risk of ischaemic stroke was inversely associated with consumption of fruit and vegetables, dietary fibre, and dairy foods, while risk of haemorrhagic stroke was positively associated with egg consumption. The apparent differences in the associations highlight the importance of examining ischaemic and haemorrhagic stroke subtypes separately.
Published: 2020
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215. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author: Erzurumluoglu, A. Mesut, Liu, Mengzhen, Jackson, Victoria E., Barnes, Daniel R., Datta, Gargi, Melbourne, Carl A., Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C., Asselbergs, Folkert W., Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L, Brazel, David M, Chambers, John C, Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi-Ling, David, Sean P, de Boer, Rudolf A, de Leeuw, Christiaan A, Dennis, Joe G, Dominiczak, Anna F, Dunning, Alison M, Easton, Douglas F, Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D, Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J, Haessler, Jeff, Haiman, Christopher, Hallmans, Göran, Hammerschlag, Anke R, Harris, Sarah E, Hattersley, Andrew, Heath, Andrew, Hsu, Chris, Iacono, William G, Kanoni, Stavroula, Kapoor, Manav, Kaprio, Jaakko, Kardia, Sharon L, Karpe, Fredrik, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kuulasmaa, Kari, Laakso, Markku, Lai, Dongbing, Langenberg, Claudia, Le, Nhung, Lettre, Guillaume, Loukola, Anu, Luan, Jian'an, Madden, Pamela A F, Mangino, Massimo, Marioni, Riccardo E, Marouli, Eirini, Marten, Jonathan, Martin, Nicholas G, McGue, Matt, Michailidou, Kyriaki, Mihailov, Evelin, Moayyeri, Alireza, Moitry, Marie, Müller-Nurasyid, Martina, Naheed, Aliya, Nauck, Matthias, Neville, Matthew J, Nielsen, Sune Fallgaard, North, Kari, Perola, Markus, Pharoah, Paul D P, Pistis, Giorgio, Polderman, Tinca J, Posthuma, Danielle, Poulter, Neil, Qaiser, Beenish, Rasheed, Asif, Reiner, Alex, Renstrom, Frida, Rice, John, Rohde, Rebecca, Rolandsson, Olov, Samani, Nilesh J, Samuel, Maria, Schlessinger, David, Scholte, Steven H, Scott, Robert A, Sever, Peter, Shao, Yaming, Shrine, Nick, Smith, Jennifer A, Starr, John M, Stirrups, Kathleen, Stram, Danielle, Stringham, Heather M, Tachmazidou, Ioanna, Tardif, Jean-Claude, Thompson, Deborah J, Tindle, Hilary A, Tragante, Vinicius, Trompet, Stella, Turcot, Valerie, Tyrrell, Jessica, Vaartjes, Ilonca, van der Leij, Andries R, van der Meer, Peter, Varga, Tibor V, Verweij, Niek, Völzke, Henry, Wareham, Nicholas J, Warren, Helen R, Weir, David R, Weiss, Stefan, Wetherill, Leah, Yaghootkar, Hanieh, Yavas, Ersin, Jiang, Yu, Chen, Fang, Zhan, Xiaowei, Zhang, Weihua, Zhao, Wei, Zhou, Kaixin, Amouyel, Philippe, Blankenberg, Stefan, Caulfield, Mark J, Chowdhury, Rajiv, Cucca, Francesco, Deary, Ian J, Deloukas, Panos, Di Angelantonio, Emanuele, Ferrario, Marco, Ferrières, Jean, Franks, Paul W, Frayling, Tim M, Frossard, Philippe, Hall, Ian P, Hayward, Caroline, Jansson, Jan-Håkan, Jukema, J Wouter, Kee, Frank, Männistö, Satu, Metspalu, Andres, Munroe, Patricia B, Nordestgaard, Børge Grønne, Palmer, Colin N A, Salomaa, Veikko, Sattar, Naveed, Spector, Timothy, Strachan, David Peter, van der Harst, Pim, Zeggini, Eleftheria, Saleheen, Danish, Butterworth, Adam S, Wain, Louise V, Abecasis, Goncalo R, Danesh, John, Tobin, Martin D, Vrieze, Scott, Liu, Dajiang J, Howson, Joanna M M, Erzurumluoglu, A. Mesut, Liu, Mengzhen, Jackson, Victoria E., Barnes, Daniel R., Datta, Gargi, Melbourne, Carl A., Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C., Asselbergs, Folkert W., Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L, Brazel, David M, Chambers, John C, Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi-Ling, David, Sean P, de Boer, Rudolf A, de Leeuw, Christiaan A, Dennis, Joe G, Dominiczak, Anna F, Dunning, Alison M, Easton, Douglas F, Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D, Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J, Haessler, Jeff, Haiman, Christopher, Hallmans, Göran, Hammerschlag, Anke R, Harris, Sarah E, Hattersley, Andrew, Heath, Andrew, Hsu, Chris, Iacono, William G, Kanoni, Stavroula, Kapoor, Manav, Kaprio, Jaakko, Kardia, Sharon L, Karpe, Fredrik, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kuulasmaa, Kari, Laakso, Markku, Lai, Dongbing, Langenberg, Claudia, Le, Nhung, Lettre, Guillaume, Loukola, Anu, Luan, Jian'an, Madden, Pamela A F, Mangino, Massimo, Marioni, Riccardo E, Marouli, Eirini, Marten, Jonathan, Martin, Nicholas G, McGue, Matt, Michailidou, Kyriaki, Mihailov, Evelin, Moayyeri, Alireza, Moitry, Marie, Müller-Nurasyid, Martina, Naheed, Aliya, Nauck, Matthias, Neville, Matthew J, Nielsen, Sune Fallgaard, North, Kari, Perola, Markus, Pharoah, Paul D P, Pistis, Giorgio, Polderman, Tinca J, Posthuma, Danielle, Poulter, Neil, Qaiser, Beenish, Rasheed, Asif, Reiner, Alex, Renstrom, Frida, Rice, John, Rohde, Rebecca, Rolandsson, Olov, Samani, Nilesh J, Samuel, Maria, Schlessinger, David, Scholte, Steven H, Scott, Robert A, Sever, Peter, Shao, Yaming, Shrine, Nick, Smith, Jennifer A, Starr, John M, Stirrups, Kathleen, Stram, Danielle, Stringham, Heather M, Tachmazidou, Ioanna, Tardif, Jean-Claude, Thompson, Deborah J, Tindle, Hilary A, Tragante, Vinicius, Trompet, Stella, Turcot, Valerie, Tyrrell, Jessica, Vaartjes, Ilonca, van der Leij, Andries R, van der Meer, Peter, Varga, Tibor V, Verweij, Niek, Völzke, Henry, Wareham, Nicholas J, Warren, Helen R, Weir, David R, Weiss, Stefan, Wetherill, Leah, Yaghootkar, Hanieh, Yavas, Ersin, Jiang, Yu, Chen, Fang, Zhan, Xiaowei, Zhang, Weihua, Zhao, Wei, Zhou, Kaixin, Amouyel, Philippe, Blankenberg, Stefan, Caulfield, Mark J, Chowdhury, Rajiv, Cucca, Francesco, Deary, Ian J, Deloukas, Panos, Di Angelantonio, Emanuele, Ferrario, Marco, Ferrières, Jean, Franks, Paul W, Frayling, Tim M, Frossard, Philippe, Hall, Ian P, Hayward, Caroline, Jansson, Jan-Håkan, Jukema, J Wouter, Kee, Frank, Männistö, Satu, Metspalu, Andres, Munroe, Patricia B, Nordestgaard, Børge Grønne, Palmer, Colin N A, Salomaa, Veikko, Sattar, Naveed, Spector, Timothy, Strachan, David Peter, van der Harst, Pim, Zeggini, Eleftheria, Saleheen, Danish, Butterworth, Adam S, Wain, Louise V, Abecasis, Goncalo R, Danesh, John, Tobin, Martin D, Vrieze, Scott, Liu, Dajiang J, and Howson, Joanna M M
Abstract: Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
Published: 2020
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216. Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes : EPIC-InterAct case-cohort study in eight European countries

Author: Zheng, Ju-Sheng, Sharp, Stephen J., Imamura, Fumiaki, Chowdhury, Rajiv, Gundersen, Thomas E., Steur, Marinka, Sluijs, Ivonne, Schouw, Yvonne T. van der, Agudo, Antonio, Aune, Dagfinn, Barricarte, Aurelio, Boeing, Heiner, Chirlaque, Maria -Dolores, Dorronsoro, Miren, Freisling, Heinz, El-Fatouhi, Douae, Franks, Paul W., Fagherazzi, Guy, Grioni, Sara, Gunter, Marc J., Kyro, Cecilie, Katzke, Verena, Kuhn, Tilman, Khaw, Kay-Tee, Laouali, Nasser, Masala, Giovanna, Nilsson, Peter M., Overvad, Kim, Panico, Salvatore, Papier, Keren, Quiros, J. Ramon, Rolandsson, Olov, Redondo-Sanchez, Daniel, Ricceri, Fulvio, Schulze, Matthias B., Spijkerman, Annemieke M. W., Tjonneland, Anne, Tong, Tammy Y. N., Tumino, Rosario, Weiderpass, Elisabete, John, Danesh, Butterworth, Adam S., Riboli, Elio, Forouhi, Nita G., Wareham, Nicholas J., Zheng, Ju-Sheng, Sharp, Stephen J., Imamura, Fumiaki, Chowdhury, Rajiv, Gundersen, Thomas E., Steur, Marinka, Sluijs, Ivonne, Schouw, Yvonne T. van der, Agudo, Antonio, Aune, Dagfinn, Barricarte, Aurelio, Boeing, Heiner, Chirlaque, Maria -Dolores, Dorronsoro, Miren, Freisling, Heinz, El-Fatouhi, Douae, Franks, Paul W., Fagherazzi, Guy, Grioni, Sara, Gunter, Marc J., Kyro, Cecilie, Katzke, Verena, Kuhn, Tilman, Khaw, Kay-Tee, Laouali, Nasser, Masala, Giovanna, Nilsson, Peter M., Overvad, Kim, Panico, Salvatore, Papier, Keren, Quiros, J. Ramon, Rolandsson, Olov, Redondo-Sanchez, Daniel, Ricceri, Fulvio, Schulze, Matthias B., Spijkerman, Annemieke M. W., Tjonneland, Anne, Tong, Tammy Y. N., Tumino, Rosario, Weiderpass, Elisabete, John, Danesh, Butterworth, Adam S., Riboli, Elio, Forouhi, Nita G., and Wareham, Nicholas J.
Abstract: Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. Design: Prospective case-cohort study. Setting: Populations from eight European countries. Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. Main outcome measure: Incident type 2 diabetes. Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers
Published: 2020
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217. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Author: Li, Chen, Stoma, Svetlana, Lotta, Luca A., Warner, Sophie, Albrecht, Eva, Allione, Alessandra, Arp, Pascal P., Broer, Linda, Buxton, Jessica L., Da Silva Couto Alves, Alexessander, Deelen, Joris, Fedko, Iryna O., Gordon, Scott D., Jiang, Tao, Karlsson, Robert, Kerrison, Nicola, Loe, Taylor K., Mangino, Massimo, Milaneschi, Yuri, Miraglio, Benjamin, Pervjakova, Natalia, Russo, Alessia, Surakka, Ida, van der Spek, Ashley, Verhoeven, Josine E., Amin, Najaf, Beekman, Marian, Blakemore, Alexandra I., Canzian, Federico, Hamby, Stephen E., Hottenga, Jouke-Jan, Jones, Peter D., Jousilahti, Pekka, Mägi, Reedik, Medland, Sarah E., Montgomery, Grant W., Nyholt, Dale R., Perola, Markus, Pietiläinen, Kirsi H., Salomaa, Veikko, Sillanpää, Elina, Suchiman, H. Eka, van Heemst, Diana, Willemsen, Gonneke, Agudo, Antonio, Boeing, Heiner, Boomsma, Dorret I., Chirlaque, Maria-Dolores, Fagherazzi, Guy, Ferrari, Pietro, Franks, Paul W., Gieger, Christian, Eriksson, Johan Gunnar, Gunter, Marc, Hagg, Sara, Hovatta, Iiris, Imaz, Liher, Kaprio, Jaakko, Kaaks, Rudolf, Key, Timothy, Krogh, Vittorio, Martin, Nicholas G., Melander, Olle, Metspalu, Andres, Moreno, Concha, Onland-Moret, N. Charlotte, Nilsson, Peter, Ong, Ken K., Overvad, Kim, Palli, Domenico, Panico, Salvatore, Pedersen, Nancy L., Penninx, Brenda W. J. H., Quirós, J. Ramón, Riitta Jarvelin, Marjo, Rodríguez-Barranco, Miguel, Scott, Robert A., Severi, Gianluca, Slagboom, P. Eline, Spector, Tim D., Tjonneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Uitterlinden, André G., van der Schouw, Yvonne T., van Duijn, Cornelia M., Weiderpass, Elisabete, Denchi, Eros Lazzerini, Matullo, Giuseppe, Butterworth, Adam S., Danesh, John, Samani, Nilesh J., Wareham, Nicholas J., Nelson, Christopher P., Langenberg, Claudia, Codd, Veryan, Li, Chen, Stoma, Svetlana, Lotta, Luca A., Warner, Sophie, Albrecht, Eva, Allione, Alessandra, Arp, Pascal P., Broer, Linda, Buxton, Jessica L., Da Silva Couto Alves, Alexessander, Deelen, Joris, Fedko, Iryna O., Gordon, Scott D., Jiang, Tao, Karlsson, Robert, Kerrison, Nicola, Loe, Taylor K., Mangino, Massimo, Milaneschi, Yuri, Miraglio, Benjamin, Pervjakova, Natalia, Russo, Alessia, Surakka, Ida, van der Spek, Ashley, Verhoeven, Josine E., Amin, Najaf, Beekman, Marian, Blakemore, Alexandra I., Canzian, Federico, Hamby, Stephen E., Hottenga, Jouke-Jan, Jones, Peter D., Jousilahti, Pekka, Mägi, Reedik, Medland, Sarah E., Montgomery, Grant W., Nyholt, Dale R., Perola, Markus, Pietiläinen, Kirsi H., Salomaa, Veikko, Sillanpää, Elina, Suchiman, H. Eka, van Heemst, Diana, Willemsen, Gonneke, Agudo, Antonio, Boeing, Heiner, Boomsma, Dorret I., Chirlaque, Maria-Dolores, Fagherazzi, Guy, Ferrari, Pietro, Franks, Paul W., Gieger, Christian, Eriksson, Johan Gunnar, Gunter, Marc, Hagg, Sara, Hovatta, Iiris, Imaz, Liher, Kaprio, Jaakko, Kaaks, Rudolf, Key, Timothy, Krogh, Vittorio, Martin, Nicholas G., Melander, Olle, Metspalu, Andres, Moreno, Concha, Onland-Moret, N. Charlotte, Nilsson, Peter, Ong, Ken K., Overvad, Kim, Palli, Domenico, Panico, Salvatore, Pedersen, Nancy L., Penninx, Brenda W. J. H., Quirós, J. Ramón, Riitta Jarvelin, Marjo, Rodríguez-Barranco, Miguel, Scott, Robert A., Severi, Gianluca, Slagboom, P. Eline, Spector, Tim D., Tjonneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Uitterlinden, André G., van der Schouw, Yvonne T., van Duijn, Cornelia M., Weiderpass, Elisabete, Denchi, Eros Lazzerini, Matullo, Giuseppe, Butterworth, Adam S., Danesh, John, Samani, Nilesh J., Wareham, Nicholas J., Nelson, Christopher P., Langenberg, Claudia, and Codd, Veryan
Abstract: Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Published: 2020
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218. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases : a multinational cohort study

Author: Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S., Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C., Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y. N., Schmidt, Julie A., Tzoulaki, Ioanna, Tsilidis, Konstantinos K., Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H. Susan J., Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J., Gunter, Marc J., Ferrari, Pietro, Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S., Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C., Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y. N., Schmidt, Julie A., Tzoulaki, Ioanna, Tsilidis, Konstantinos K., Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H. Susan J., Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J., Gunter, Marc J., and Ferrari, Pietro
Abstract: BACKGROUND: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. METHODS: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. RESULTS: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and
Published: 2020
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219. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study

Author: Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S, Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C, Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y N, Schmidt, Julie A, Tzoulaki, Ioanna, Tsilidis, Konstantinos K, Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H Susan J, Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J, Gunter, Marc J, Ferrari, Pietro, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S, Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C, Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y N, Schmidt, Julie A, Tzoulaki, Ioanna, Tsilidis, Konstantinos K, Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H Susan J, Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J, Gunter, Marc J, and Ferrari, Pietro
Published: 2020

220. Large genome-wide association study identifies three novel risk variants for restless legs syndrome

Author: Didriksen, Maria, Nawaz, Muhammad Sulaman, Dowsett, Joseph, Bell, Steven, Erikstrup, Christian, Pedersen, Ole B., Sørensen, Erik, Jennum, Poul J., Burgdorf, Kristoffer S., Burchell, Brendan, Butterworth, Adam S., Soranzo, Nicole, Rye, David B., Trotti, Lynn Marie, Saini, Prabhjyot, Stefansdottir, Lilja, Magnusson, Sigurdur H., Thorleifsson, Gudmar, Sigmundsson, Thordur, Sigurdsson, Albert P., Van Den Hurk, Katja, Quee, Franke, Tanck, Michael W.T., Ouwehand, Willem H., Roberts, David J., Earley, Eric J., Busch, Michael P., Mast, Alan E., Page, Grier P., Danesh, John, Di Angelantonio, Emanuele, Stefansson, Hreinn, Ullum, Henrik, Stefansson, Kari, Didriksen, Maria, Nawaz, Muhammad Sulaman, Dowsett, Joseph, Bell, Steven, Erikstrup, Christian, Pedersen, Ole B., Sørensen, Erik, Jennum, Poul J., Burgdorf, Kristoffer S., Burchell, Brendan, Butterworth, Adam S., Soranzo, Nicole, Rye, David B., Trotti, Lynn Marie, Saini, Prabhjyot, Stefansdottir, Lilja, Magnusson, Sigurdur H., Thorleifsson, Gudmar, Sigmundsson, Thordur, Sigurdsson, Albert P., Van Den Hurk, Katja, Quee, Franke, Tanck, Michael W.T., Ouwehand, Willem H., Roberts, David J., Earley, Eric J., Busch, Michael P., Mast, Alan E., Page, Grier P., Danesh, John, Di Angelantonio, Emanuele, Stefansson, Hreinn, Ullum, Henrik, and Stefansson, Kari
Abstract: Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10−18), rs10068599-T (OR = 1.09, P = 6.9 × 10−10) and rs10769894-A (OR = 0.90, P = 9.4 × 10−14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed.
Published: 2020

221. Glycemic index, glycemic load, and risk of coronary heart disease:A pan-European cohort study

Author: Sieri, Sabina, Agnoli, Claudia, Grioni, Sara, Weiderpass, Elisabete, Mattiello, Amalia, Sluijs, Ivonne, Sanchez, Maria Jose, Jakobsen, Marianne Uhre, Sweeting, Michael, van der Schouw, Yvonne T., Nilsson, Lena Maria, Wennberg, Patrik, Katzke, Verena A., Kühn, Tilman, Overvad, Kim, Tong, Tammy Y.N., Conchi, Moreno Iribas, Quirós, José Ramón, García-Torrecillas, Juan Manuel, Mokoroa, Olatz, Gómez, Jesús Humberto, Tjønneland, Anne, Sonestedt, Emiliy, Trichopoulou, Antonia, Karakatsani, Anna, Valanou, Elissavet, Boer, Jolanda M.A., Monique Verschuren, W. M., Boutron-Ruault, Marie Christine, Fagherazzi, Guy, Madika, Anne Laure, Bergmann, Manuela M., Schulze, Matthias B., Ferrari, Pietro, Freisling, Heinz, Lennon, Hannah, Sacerdote, Carlotta, Masala, Giovanna, Tumino, Rosario, Riboli, Elio, Wareham, Nicholas J., Danesh, John, Forouhi, Nita G., Butterworth, Adam S., Krogh, Vittorio, Sieri, Sabina, Agnoli, Claudia, Grioni, Sara, Weiderpass, Elisabete, Mattiello, Amalia, Sluijs, Ivonne, Sanchez, Maria Jose, Jakobsen, Marianne Uhre, Sweeting, Michael, van der Schouw, Yvonne T., Nilsson, Lena Maria, Wennberg, Patrik, Katzke, Verena A., Kühn, Tilman, Overvad, Kim, Tong, Tammy Y.N., Conchi, Moreno Iribas, Quirós, José Ramón, García-Torrecillas, Juan Manuel, Mokoroa, Olatz, Gómez, Jesús Humberto, Tjønneland, Anne, Sonestedt, Emiliy, Trichopoulou, Antonia, Karakatsani, Anna, Valanou, Elissavet, Boer, Jolanda M.A., Monique Verschuren, W. M., Boutron-Ruault, Marie Christine, Fagherazzi, Guy, Madika, Anne Laure, Bergmann, Manuela M., Schulze, Matthias B., Ferrari, Pietro, Freisling, Heinz, Lennon, Hannah, Sacerdote, Carlotta, Masala, Giovanna, Tumino, Rosario, Riboli, Elio, Wareham, Nicholas J., Danesh, John, Forouhi, Nita G., Butterworth, Adam S., and Krogh, Vittorio
Abstract: Background: High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. Objectives: The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes. Methods: This large prospective study-the European Prospective Investigation into Cancer and Nutrition-consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models. Results: After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m2) =25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI <25 [HR: 1.09 (95% CI: 0.98, 1.22) per 50 g/d) (P-interaction = 0.022). The GL-CHD association did not differ between men [HR: 1.19 (95% CI: 1.08, 1.30) per 50 g/d] and women [HR: 1.22 (95% CI: 1.07, 1.40) per 50 g/d] (test for interaction not significant). GI was associated with CHD risk only in the continuous model [HR: 1.04 (95% CI: 1.00, 1.08) per 5 units/d]. High available carbohydrate was associated with greater CHD risk [HR: 1.11 (95% CI: 1.03, 1.18) per 50 g/d]. High sugar intake was associated with greater CHD risk [HR: 1.09 (95% CI: 1.02, 1.17) per 50 g/d]. Conclusions: This large pan-European study provides robust additional support for the hypothesis that a diet that induces a high glucose response is associated with greater CHD risk.
Published: 2020

222. The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke:a prospective study of 418 329 participants in the EPIC cohort across nine European countries

Author: Tong, Tammy Y. N., Appleby, Paul N., Key, Timothy J., Dahm, Christina C., Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Katzke, Verena, Kuhn, Tilman, Boeing, Heiner, Karakatsani, Anna, Peppa, Eleni, Trichopoulou, Antonia, Weiderpass, Elisabete, Masala, Giovanna, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Boer, Jolanda M. A., Verschuren, W. M. Monique, Quiros, J. Ramon, Agudo, Antonio, Rodriguez-Barranco, Miguel, Imaz, Liher, Chirlaque, Maria-Dolores, Moreno-Iribas, Conchi, Engstrom, Gunnar, Sonestedt, Emily, Lind, Marcus, Otten, Julia, Khaw, Kay-Tee, Aune, Dagfinn, Riboli, Elio, Wareham, Nicholas J., Imamura, Fumiaki, Forouhi, Nita G., di Angelantonio, Emanuele, Wood, Angela M., Butterworth, Adam S., Perez-Cornago, Aurora, Tong, Tammy Y. N., Appleby, Paul N., Key, Timothy J., Dahm, Christina C., Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Katzke, Verena, Kuhn, Tilman, Boeing, Heiner, Karakatsani, Anna, Peppa, Eleni, Trichopoulou, Antonia, Weiderpass, Elisabete, Masala, Giovanna, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Boer, Jolanda M. A., Verschuren, W. M. Monique, Quiros, J. Ramon, Agudo, Antonio, Rodriguez-Barranco, Miguel, Imaz, Liher, Chirlaque, Maria-Dolores, Moreno-Iribas, Conchi, Engstrom, Gunnar, Sonestedt, Emily, Lind, Marcus, Otten, Julia, Khaw, Kay-Tee, Aune, Dagfinn, Riboli, Elio, Wareham, Nicholas J., Imamura, Fumiaki, Forouhi, Nita G., di Angelantonio, Emanuele, Wood, Angela M., Butterworth, Adam S., and Perez-Cornago, Aurora
Abstract: Aim To investigate the associations between major foods and dietary fibre with subtypes of stroke in a large prospective cohort.Methods and results We analysed data on 418 329 men and women from nine European countries, with an average of 12.7years of follow-up. Diet was assessed using validated country-specific questionnaires which asked about habitual intake over the past year, calibrated using 24-h recalls. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HRs) for ischaemic and haemorrhagic stroke associated with consumption of red and processed meat, poultry, fish, dairy foods, eggs, cereals, fruit and vegetables, legumes, nuts and seeds, and dietary fibre. For ischaemic stroke (4281 cases), lower risks were observed with higher consumption of fruit and vegetables combined (HR; 95% CI per 200g/day higher intake, 0.87; 0.82-0.93, P-trendConclusion Risk of ischaemic stroke was inversely associated with consumption of fruit and vegetables, dietary fibre, and dairy foods, while risk of haemorrhagic stroke was positively associated with egg consumption. The apparent differences in the associations highlight the importance of examining ischaemic and haemorrhagic stroke subtypes separately.
Published: 2020

223. The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Author: Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Zheng, Ju Sheng, Luan, Jian'an, Sofianopoulou, Eleni, Sharp, Stephen J., Day, Felix R., Imamura, Fumiaki, Gundersen, Thomas E., Lotta, Luca A., Sluijs, Ivonne, Stewart, Isobel D., Shah, Rupal L., Van Der Schouw, Yvonne T., Wheeler, Eleanor, Ardanaz, Eva, Boeing, Heiner, Dorronsoro, Miren, Dahm, Christina C., Dimou, Niki, El-Fatouhi, Douae, Franks, Paul W., Fagherazzi, Guy, Grioni, Sara, Huerta, José María, Heath, Alicia K., Hansen, Louise, Jenab, Mazda, Jakszyn, Paula, Kaaks, Rudolf, Kühn, Tilman, Khaw, Kay Tee, Laouali, Nasser, Masala, Giovanna, Nilsson, Peter M., Overvad, Kim, Olsen, Anja, Panico, Salvatore, Ramón Quirós, J., Rolandsson, Olov, Rodríguez-Barranco, Miguel, Sacerdote, Carlotta, Spijkerman, Annemieke M.W., Tong, Tammy Y.N., Tumino, Rosario, Tsilidis, Konstantinos K., Danesh, John, Riboli, Elio, Butterworth, Adam S., Langenberg, Claudia, Forouhi, Nita G., Wareham, Nicholas J., Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Zheng, Ju Sheng, Luan, Jian'an, Sofianopoulou, Eleni, Sharp, Stephen J., Day, Felix R., Imamura, Fumiaki, Gundersen, Thomas E., Lotta, Luca A., Sluijs, Ivonne, Stewart, Isobel D., Shah, Rupal L., Van Der Schouw, Yvonne T., Wheeler, Eleanor, Ardanaz, Eva, Boeing, Heiner, Dorronsoro, Miren, Dahm, Christina C., Dimou, Niki, El-Fatouhi, Douae, Franks, Paul W., Fagherazzi, Guy, Grioni, Sara, Huerta, José María, Heath, Alicia K., Hansen, Louise, Jenab, Mazda, Jakszyn, Paula, Kaaks, Rudolf, Kühn, Tilman, Khaw, Kay Tee, Laouali, Nasser, Masala, Giovanna, Nilsson, Peter M., Overvad, Kim, Olsen, Anja, Panico, Salvatore, Ramón Quirós, J., Rolandsson, Olov, Rodríguez-Barranco, Miguel, Sacerdote, Carlotta, Spijkerman, Annemieke M.W., Tong, Tammy Y.N., Tumino, Rosario, Tsilidis, Konstantinos K., Danesh, John, Riboli, Elio, Butterworth, Adam S., Langenberg, Claudia, Forouhi, Nita G., and Wareham, Nicholas J.
Published: 2020

224. Glycemic index, glycemic load, and risk of coronary heart disease: a pan-European cohort study

Author: Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, UMC Utrecht, Public Health Epidemiologie, Sieri, Sabina, Agnoli, Claudia, Grioni, Sara, Weiderpass, Elisabete, Mattiello, Amalia, Sluijs, Ivonne, Sanchez, Maria Jose, Jakobsen, Marianne Uhre, Sweeting, Michael, van der Schouw, Yvonne T., Nilsson, Lena Maria, Wennberg, Patrik, Katzke, Verena A., Kuhn, Tilman, Overvad, Kim, Tong, Tammy Y. N., Conchi, Moreno-Iribas, Ramon Quiros, Jose, Manuel Garcia-Torrecillas, Juan, Mokoroa, Olatz, Gomez, Jesus-Humberto, Tjonneland, Anne, Sonestedt, Emiliy, Trichopoulou, Antonia, Karakatsani, Anna, Valanou, Elissavet, Boer, Jolanda M. A., Verschuren, W. M. Monique, Boutron-Ruault, Marie-Christine, Fagherazzi, Guy, Madika, Anne-Laure, Bergmann, Manuela M., Schulze, Matthias B., Ferrari, Pietro, Freisling, Heinz, Lennon, Hannah, Sacerdote, Carlotta, Masala, Giovanna, Tumino, Rosario, Riboli, Elio, Wareham, Nicholas J., Danesh, John, Forouhi, Nita G., Butterworth, Adam S., Krogh, Vittorio, Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, UMC Utrecht, Public Health Epidemiologie, Sieri, Sabina, Agnoli, Claudia, Grioni, Sara, Weiderpass, Elisabete, Mattiello, Amalia, Sluijs, Ivonne, Sanchez, Maria Jose, Jakobsen, Marianne Uhre, Sweeting, Michael, van der Schouw, Yvonne T., Nilsson, Lena Maria, Wennberg, Patrik, Katzke, Verena A., Kuhn, Tilman, Overvad, Kim, Tong, Tammy Y. N., Conchi, Moreno-Iribas, Ramon Quiros, Jose, Manuel Garcia-Torrecillas, Juan, Mokoroa, Olatz, Gomez, Jesus-Humberto, Tjonneland, Anne, Sonestedt, Emiliy, Trichopoulou, Antonia, Karakatsani, Anna, Valanou, Elissavet, Boer, Jolanda M. A., Verschuren, W. M. Monique, Boutron-Ruault, Marie-Christine, Fagherazzi, Guy, Madika, Anne-Laure, Bergmann, Manuela M., Schulze, Matthias B., Ferrari, Pietro, Freisling, Heinz, Lennon, Hannah, Sacerdote, Carlotta, Masala, Giovanna, Tumino, Rosario, Riboli, Elio, Wareham, Nicholas J., Danesh, John, Forouhi, Nita G., Butterworth, Adam S., and Krogh, Vittorio
Published: 2020

225. Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries

Author: Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Zheng, Ju Sheng, Sharp, Stephen J., Imamura, Fumiaki, Chowdhury, Rajiv, Gundersen, Thomas E., Steur, Marinka, Sluijs, Ivonne, Van Der Schouw, Yvonne T., Agudo, Antonio, Aune, Dagfinn, Barricarte, Aurelio, Boeing, Heiner, Chirlaque, María Dolores, Dorronsoro, Miren, Freisling, Heinz, El-Fatouhi, Douae, Franks, Paul W., Fagherazzi, Guy, Grioni, Sara, Gunter, Marc J., Kyrø, Cecilie, Katzke, Verena, Kühn, Tilman, Khaw, Kay Tee, Laouali, Nasser, Masala, Giovanna, Nilsson, Peter M., Overvad, Kim, Panico, Salvatore, Papier, Keren, Quirós, J. Ramón, Rolandsson, Olov, Redondo-Sánchez, Daniel, Ricceri, Fulvio, Schulze, Matthias B., Spijkerman, Annemieke M.W., Tjønneland, Anne, Tong, Tammy Y.N., Tumino, Rosario, Weiderpass, Elisabete, Danesh, John, Butterworth, Adam S., Riboli, Elio, Forouhi, Nita G., Wareham, Nicholas J., Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Zheng, Ju Sheng, Sharp, Stephen J., Imamura, Fumiaki, Chowdhury, Rajiv, Gundersen, Thomas E., Steur, Marinka, Sluijs, Ivonne, Van Der Schouw, Yvonne T., Agudo, Antonio, Aune, Dagfinn, Barricarte, Aurelio, Boeing, Heiner, Chirlaque, María Dolores, Dorronsoro, Miren, Freisling, Heinz, El-Fatouhi, Douae, Franks, Paul W., Fagherazzi, Guy, Grioni, Sara, Gunter, Marc J., Kyrø, Cecilie, Katzke, Verena, Kühn, Tilman, Khaw, Kay Tee, Laouali, Nasser, Masala, Giovanna, Nilsson, Peter M., Overvad, Kim, Panico, Salvatore, Papier, Keren, Quirós, J. Ramón, Rolandsson, Olov, Redondo-Sánchez, Daniel, Ricceri, Fulvio, Schulze, Matthias B., Spijkerman, Annemieke M.W., Tjønneland, Anne, Tong, Tammy Y.N., Tumino, Rosario, Weiderpass, Elisabete, Danesh, John, Butterworth, Adam S., Riboli, Elio, Forouhi, Nita G., and Wareham, Nicholas J.
Published: 2020

226. The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke: a prospective study of 418 329 participants in the EPIC cohort across nine European countries

Author: Public Health Epidemiologie, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Tong, Tammy Y N, Appleby, Paul N, Key, Timothy J, Dahm, Christina C, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Katzke, Verena, Kühn, Tilman, Boeing, Heiner, Karakatsani, Anna, Peppa, Eleni, Trichopoulou, Antonia, Weiderpass, Elisabete, Masala, Giovanna, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Boer, Jolanda M A, Verschuren, W M Monique, Quirós, J Ramón, Agudo, Antonio, Rodríguez-Barranco, Miguel, Imaz, Liher, Chirlaque, María-Dolores, Moreno-Iribas, Conchi, Engström, Gunnar, Sonestedt, Emily, Lind, Marcus, Otten, Julia, Khaw, Kay-Tee, Aune, Dagfinn, Riboli, Elio, Wareham, Nicholas J, Imamura, Fumiaki, Forouhi, Nita G, di Angelantonio, Emanuele, Wood, Angela M, Butterworth, Adam S, Perez-Cornago, Aurora, Public Health Epidemiologie, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Tong, Tammy Y N, Appleby, Paul N, Key, Timothy J, Dahm, Christina C, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Katzke, Verena, Kühn, Tilman, Boeing, Heiner, Karakatsani, Anna, Peppa, Eleni, Trichopoulou, Antonia, Weiderpass, Elisabete, Masala, Giovanna, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Boer, Jolanda M A, Verschuren, W M Monique, Quirós, J Ramón, Agudo, Antonio, Rodríguez-Barranco, Miguel, Imaz, Liher, Chirlaque, María-Dolores, Moreno-Iribas, Conchi, Engström, Gunnar, Sonestedt, Emily, Lind, Marcus, Otten, Julia, Khaw, Kay-Tee, Aune, Dagfinn, Riboli, Elio, Wareham, Nicholas J, Imamura, Fumiaki, Forouhi, Nita G, di Angelantonio, Emanuele, Wood, Angela M, Butterworth, Adam S, and Perez-Cornago, Aurora
Published: 2020

227. Genetic Determinants of Lipids and Cardiovascular Disease Outcomes: A Wide-Angled Mendelian Randomization Investigation

Author: Allara, Elias, Morani, Gabriele, Carter, Paul, Gkatzionis, Apostolos, Zuber, Verena, Foley, Christopher N, Rees, Jessica MB, Mason, Amy M, Bell, Steven, Gill, Dipender, Lindström, Sara, Butterworth, Adam S, Di Angelantonio, Emanuele, Peters, James, Burgess, Stephen, INVENT consortium, Allara, Elias [0000-0002-1634-8330], Carter, Paul [0000-0002-9146-7540], Foley, Christopher [0000-0002-0970-2610], Mason, Amy [0000-0002-8019-0777], Bell, Steven [0000-0001-6774-3149], Butterworth, Adam [0000-0002-6915-9015], Di Angelantonio, Emanuele [0000-0001-8776-6719], Burgess, Stephen [0000-0001-5365-8760], and Apollo - University of Cambridge Repository
Subjects: Adult, Male, venous thromboembolism, aortic valve stenosis, Cholesterol, LDL, Mendelian Randomization Analysis, Middle Aged, White People, lipids, Europe, Cardiovascular Diseases, Risk Factors, Mendelian randomization, Odds Ratio, Humans, epidemiology, Female, Genetic Predisposition to Disease, Triglycerides, Aged, Genome-Wide Association Study
Abstract: BACKGROUND: Evidence from randomized trials has shown that therapies that lower LDL (low-density lipoprotein)-cholesterol and triglycerides reduce coronary artery disease (CAD) risk. However, there is still uncertainty about their effects on other cardiovascular outcomes. We therefore performed a systematic investigation of causal relationships between circulating lipids and cardiovascular outcomes using a Mendelian randomization approach. METHODS: In the primary analysis, we performed 2-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188 577 participants, and genetic associations with cardiovascular outcomes from 367 703 participants in UK Biobank. RESULTS: For LDL-cholesterol, in addition to the expected positive associations with CAD risk (odds ratio [OR] per 1 SD increase, 1.45 [95% CI, 1.35-1.57]) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically predicted LDL-cholesterol with abdominal aortic aneurysm (OR, 1.75 [95% CI, 1.40-2.17]) and aortic valve stenosis (OR, 1.46 [95% CI, 1.25-1.70]). Genetically predicted triglyceride levels were positively associated with CAD (OR, 1.25 [95% CI, 1.12-1.40]), aortic valve stenosis (OR, 1.29 [95% CI, 1.04-1.61]), and hypertension (OR, 1.17 [95% CI, 1.07-1.27]), but inversely associated with venous thromboembolism (OR, 0.79 [95% CI, 0.67-0.93]) and hemorrhagic stroke (OR, 0.78 [95% CI, 0.62-0.98]). We also found positive associations of genetically predicted LDL-cholesterol and triglycerides with heart failure that appeared to be mediated by CAD. CONCLUSIONS: Lowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis but may increase thromboembolic risk.
Published: 2019

228. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author: Malik, Rainer, Chauhan, Ganesh, Anderson, Christopher D, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie L M, Tanislav, Christian, Tatlisumak, Turgut, Chong, Michael, Taylor, Kent D, Thijs, Vincent N S, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Adams, Hieab H H, Wassertheil-Smoller, Sylvia, Wilson, James G, Wiggins, Kerri L, Yang, Qiong, Yusuf, Salim, Consortium, AFGen, Epidemiology, Cohorts for Heart and Aging Research in Genomic, Pressure, International Genomics of Blood, Consortium, INVENT, STARNET, Ago, Tetsuro, Bis, Joshua C, Pastinen, Tomi, Ruusalepp, Arno, Schadt, Eric E, Koplev, Simon, Björkegren, Johan L M, Codoni, Veronica, Civelek, Mete, Smith, Nicholas L, Trégouët, David A, Almgren, Peter, Christophersen, Ingrid E, Roselli, Carolina, Lubitz, Steven A, Ellinor, Patrick T, Tai, E Shyong, Kooner, Jaspal S, Kato, Norihiro, He, Jiang, van der Harst, Pim, Elliott, Paul, Amouyel, Philippe, Chambers, John C, Takeuchi, Fumihiko, Johnson, Andrew D, Group, BioBank Japan Cooperative Hospital, Consortium, COMPASS, Consortium, EPIC-CVD, Consortium, EPIC-InterAct, Consortium, International Stroke Genetics, Consortium, METASTROKE, Consortium, Neurology Working Group of the CHARGE, Ay, Hakan, Network, NINDS Stroke Genetics, Study, UK Young Lacunar DNA, Consortium, MEGASTROKE, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez-Cadenas, Israel, Longstreth, W. T., Rolfs, Arndt, Bartz, Traci M, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Benavente, Oscar R, Fornage, Myriam, Markus, Hugh S, Howson, Joanna M M, Kamatani, Yoichiro, Debette, Stephanie, Dichgans, Martin, Traylor, Matthew, Sargurupremraj, Muralidharan, Bevan, Steve, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chasman, Daniel I, Chen, Wei-Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul I W, DeStefano, Anita L, Hoed, Marcel den, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Heckbert, Susan R, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I, Ikram, M Arfan, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei-Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O'Donnell, Martin J, Psaty, Bruce M, Pulit, Sara L, Rannikmäe, Kristiina, Reiner, Alexander P, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Ridker, Paul M, Rost, Natalia S, Rothwell, Peter M, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu-Ching, Choi, Seung Hoan, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean-François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, den Hoed, Marcel, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Liu, Yong Mei, Lopez, Oscar L, Makoto, Hirata, Martinez-Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Peddareddygari, Leema Reddy, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano-Tárraga, Carolina, Stanne, Tara, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres-Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles D A, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathology, Epidemiology, Radiology & Nuclear Medicine, Cardiovascular Centre (CVC), Universitat de Barcelona, Traylor, Matthew [0000-0001-6624-8621], Okada, Yukinori [0000-0002-0311-8472], Rutten-Jacobs, Loes [0000-0003-3223-885X], van der Laan, Sander W [0000-0001-6888-1404], Adams, Hieab HH [0000-0003-3687-2508], Almgren, Peter [0000-0002-0473-0241], Amouyel, Philippe [0000-0001-9088-234X], Correa, Adolfo [0000-0002-9501-600X], Cruchaga, Carlos [0000-0002-0276-2899], den Hoed, Marcel [0000-0001-8081-428X], Gustafsson, Stefan [0000-0001-5894-0351], Havulinna, Aki S [0000-0002-4787-8959], Ikram, M Arfan [0000-0003-0372-8585], Jukema, J Wouter [0000-0002-3246-8359], Kanai, Masahiro [0000-0001-5165-4408], Lewis, Cathryn M [0000-0002-8249-8476], Lin, Wei-Yu [0000-0002-9267-7988], Magnusson, Patrik K [0000-0002-7315-7899], Pulit, Sara L [0000-0002-2502-3669], Wiggins, Kerri L [0000-0003-2749-1279], Yang, Qiong [0000-0002-3658-1375], Schadt, Eric E [0000-0002-7892-8808], Koplev, Simon [0000-0002-8586-5614], Civelek, Mete [0000-0002-8141-0284], Trégouët, David A [0000-0001-9084-7800], Christophersen, Ingrid E [0000-0002-6141-4712], Roselli, Carolina [0000-0001-5267-6756], Ellinor, Patrick T [0000-0002-2067-0533], van der Harst, Pim [0000-0002-2713-686X], Elliott, Paul [0000-0002-7511-5684], Takeuchi, Fumihiko [0000-0003-3185-5661], Jern, Christina [0000-0002-7531-2354], Saleheen, Danish [0000-0001-6193-020X], Kamatani, Yoichiro [0000-0001-8748-5597], Dichgans, Martin [0000-0002-0654-387X], and Apollo - University of Cambridge Repository
Subjects: Male, 0301 basic medicine, COMPASS Consortium, Linkage disequilibrium, Candidate gene, UK Young Lacunar DNA Study, Genome-wide association study, SEPIA, Linkage Disequilibrium, Epigenesis, Genetic, classification [Stroke], International Stroke Genetics Consortium (ISGC), 0302 clinical medicine, INDEL Mutation, HEMORRHAGIC STROKE, Risk Factors, Pleiotropy, Databases, Genetic, Neurology Working Group of the CHARGE Consortium, WHITE-MATTER HYPERINTENSITIES, Gene Regulatory Networks, Stroke, Genetics & Heredity, Genetics, International Genomics of Blood Pressure (iGEN-BP) Consortium, physiopathology [Stroke], AFGen Consortium, 11 Medical And Health Sciences, Genomics, 3. Good health, [MEGASTROKE Consortium], ISCHEMIC-STROKE, VINTAGE, genetics [Stroke], CORONARY-ARTERY-DISEASE, Medical genetics, Female, EPIC-InterAct Consortium, MEGASTROKE Consortium, Life Sciences & Biomedicine, Gens, medicine.medical_specialty, SUSCEPTIBILITY LOCI, STARNET, INVENT Consortium, SMALL-VESSEL DISEASE, Biology, Polymorphism, Single Nucleotide, EPIC-CVD Consortium, Article, Chromosomes, HUMAN GENETIC-VARIATION, NINDS Stroke Genetics Network (SiGN), 03 medical and health sciences, ddc:570, Genetic variation, medicine, Humans, Genetic Predisposition to Disease, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Science & Technology, Models, Genetic, COMPLEX TRAITS, Computational Biology, 06 Biological Sciences, medicine.disease, METASTROKE Consortium, Human genetics, Cromosomes, BioBank Japan Cooperative Hospital Group, Genòmica, 030104 developmental biology, Genes, Genetic Loci, ATRIAL-FIBRILLATION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SUDDEN CARDIAC DEATH, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke sub-types. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.
Published: 2018

229. Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses

Author: Sun, Luanluan, primary, Pennells, Lisa, additional, Kaptoge, Stephen, additional, Nelson, Christopher P., additional, Ritchie, Scott C., additional, Abraham, Gad, additional, Arnold, Matthew, additional, Bell, Steven, additional, Bolton, Thomas, additional, Burgess, Stephen, additional, Dudbridge, Frank, additional, Guo, Qi, additional, Sofianopoulou, Eleni, additional, Stevens, David, additional, Thompson, John R., additional, Butterworth, Adam S., additional, Wood, Angela, additional, Danesh, John, additional, Samani, Nilesh J., additional, Inouye, Michael, additional, and Di Angelantonio, Emanuele, additional
Published: 2021
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230. Metabolic profiling of angiopoietin-like protein 3 and 4 inhibition: a drug-target Mendelian randomization analysis

Author: Wang, Qin, primary, Oliver-Williams, Clare, additional, Raitakari, Olli T, additional, Viikari, Jorma, additional, Lehtimäki, Terho, additional, Kähönen, Mika, additional, Järvelin, Marjo-Riitta, additional, Salomaa, Veikko, additional, Perola, Markus, additional, Danesh, John, additional, Kettunen, Johannes, additional, Butterworth, Adam S, additional, Holmes, Michael V, additional, and Ala-Korpela, Mika, additional
Published: 2020
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231. Rare and common genetic determinants of metabolic individuality and their effects on human health

Author: Surendran, Praveen, Stewart, Isobel D., Au Yeung, Victoria P. W., Pietzner, Maik, Raffler, Johannes, Wörheide, Maria A., Li, Chen, Smith, Rebecca F., Wittemans, Laura B. L., Bomba, Lorenzo, Menni, Cristina, Zierer, Jonas, Rossi, Niccolò, Sheridan, Patricia A., Watkins, Nicholas A., Mangino, Massimo, Hysi, Pirro G., Di Angelantonio, Emanuele, Falchi, Mario, Spector, Tim D., Soranzo, Nicole, Michelotti, Gregory A., Arlt, Wiebke, Lotta, Luca A., Denaxas, Spiros, Hemingway, Harry, Gamazon, Eric R., Howson, Joanna M. M., Wood, Angela M., Danesh, John, Wareham, Nicholas J., Kastenmüller, Gabi, Fauman, Eric B., Suhre, Karsten, Butterworth, Adam S., and Langenberg, Claudia
Abstract: Garrod’s concept of ‘chemical individuality’ has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant–metabolite associations (P< 1.25 × 10−11) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant–metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects (DPYDand SRD5A2). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships.
Published: 2022
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232. Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases

Author: Khoury, Muin J., primary, Bertram, Lars, additional, Boffetta, Paolo, additional, Butterworth, Adam S., additional, Chanock, Stephen J., additional, Dolan, Siobhan M., additional, Fortier, Isabel, additional, Garcia-Closas, Montserrat, additional, Gwinn, Marta, additional, Higgins, Julian P. T., additional, Janssens, A. Cecile J. W., additional, Ostell, James M., additional, Owen, Ryan P., additional, Pagon, Roberta A., additional, Rebbeck, Timothy R., additional, Rothman, Nathaniel, additional, Bernstein, Jonine L., additional, Burton, Paul R., additional, Campbell, Harry, additional, Chokkalingam, Anand P., additional, Furberg, Helena, additional, Little, Julian, additional, O’Brien, Thomas R., additional, Seminara, Daniela, additional, Vineis, Paolo, additional, Winn, Deborah M., additional, Yu, Wei, additional, and Ioannidis, John P. A., additional
Published: 2009
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233. Coronary heart disease

Author: Butterworth, Adam S., primary, Higgins, Julian P. T., additional, Sarwar, Nadeem, additional, and Danesh, John, additional
Published: 2009
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234. Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Perez-Cornago, Aurora, primary, Crowe, Francesca L, additional, Appleby, Paul N, additional, Bradbury, Kathryn E, additional, Wood, Angela M, additional, Jakobsen, Marianne Uhre, additional, Johnson, Laura, additional, Sacerdote, Carlotta, additional, Steur, Marinka, additional, Weiderpass, Elisabete, additional, Würtz, Anne Mette L, additional, Kühn, Tilman, additional, Katzke, Verena, additional, Trichopoulou, Antonia, additional, Karakatsani, Anna, additional, La Vecchia, Carlo, additional, Masala, Giovanna, additional, Tumino, Rosario, additional, Panico, Salvatore, additional, Sluijs, Ivonne, additional, Skeie, Guri, additional, Imaz, Liher, additional, Petrova, Dafina, additional, Quirós, J Ramón, additional, Yohar, Sandra Milena Colorado, additional, Jakszyn, Paula, additional, Melander, Olle, additional, Sonestedt, Emily, additional, Andersson, Jonas, additional, Wennberg, Maria, additional, Aune, Dagfinn, additional, Riboli, Elio, additional, Schulze, Matthias B, additional, di Angelantonio, Emanuele, additional, Wareham, Nicholas J, additional, Danesh, John, additional, Forouhi, Nita G, additional, Butterworth, Adam S, additional, and Key, Timothy J, additional
Published: 2020
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235. Large genome-wide association study identifies three novel risk variants for restless legs syndrome

Author: Didriksen, Maria, primary, Nawaz, Muhammad Sulaman, additional, Dowsett, Joseph, additional, Bell, Steven, additional, Erikstrup, Christian, additional, Pedersen, Ole B., additional, Sørensen, Erik, additional, Jennum, Poul J., additional, Burgdorf, Kristoffer S., additional, Burchell, Brendan, additional, Butterworth, Adam S., additional, Soranzo, Nicole, additional, Rye, David B., additional, Trotti, Lynn Marie, additional, Saini, Prabhjyot, additional, Stefansdottir, Lilja, additional, Magnusson, Sigurdur H., additional, Thorleifsson, Gudmar, additional, Sigmundsson, Thordur, additional, Sigurdsson, Albert P., additional, Van Den Hurk, Katja, additional, Quee, Franke, additional, Tanck, Michael W. T., additional, Ouwehand, Willem H., additional, Roberts, David J., additional, Earley, Eric J., additional, Busch, Michael P., additional, Mast, Alan E., additional, Page, Grier P., additional, Danesh, John, additional, Di Angelantonio, Emanuele, additional, Stefansson, Hreinn, additional, Ullum, Henrik, additional, and Stefansson, Kari, additional
Published: 2020
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236. 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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237. Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations

Author: Zheng, Ju-Sheng, primary, Luan, Jian’an, additional, Sofianopoulou, Eleni, additional, Imamura, Fumiaki, additional, Stewart, Isobel D., additional, Day, Felix R., additional, Pietzner, Maik, additional, Wheeler, Eleanor, additional, Lotta, Luca A., additional, Gundersen, Thomas E., additional, Amiano, Pilar, additional, Ardanaz, Eva, additional, Chirlaque, María-Dolores, additional, Fagherazzi, Guy, additional, Franks, Paul W., additional, Kaaks, Rudolf, additional, Laouali, Nasser, additional, Mancini, Francesca Romana, additional, Nilsson, Peter M., additional, Onland-Moret, N. Charlotte, additional, Olsen, Anja, additional, Overvad, Kim, additional, Panico, Salvatore, additional, Palli, Domenico, additional, Ricceri, Fulvio, additional, Rolandsson, Olov, additional, Spijkerman, Annemieke M.W., additional, Sánchez, María-José, additional, Schulze, Matthias B., additional, Sala, Núria, additional, Sieri, Sabina, additional, Tjønneland, Anne, additional, Tumino, Rosario, additional, van der Schouw, Yvonne T., additional, Weiderpass, Elisabete, additional, Riboli, Elio, additional, Danesh, John, additional, Butterworth, Adam S., additional, Sharp, Stephen J., additional, Langenberg, Claudia, additional, Forouhi, Nita G., additional, and Wareham, Nicholas J., additional
Published: 2020
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238. ACE inhibition and cardiometabolic risk factors, lungACE2andTMPRSS2gene expression, and plasma ACE2 levels: a Mendelian randomization study

Author: Gill, Dipender, primary, Arvanitis, Marios, additional, Carter, Paul, additional, Hernández Cordero, Ana I., additional, Jo, Brian, additional, Karhunen, Ville, additional, Larsson, Susanna C., additional, Li, Xuan, additional, Lockhart, Sam M., additional, Mason, Amy, additional, Pashos, Evanthia, additional, Saha, Ashis, additional, Tan, Vanessa Y., additional, Zuber, Verena, additional, Bossé, Yohan, additional, Fahle, Sarah, additional, Hao, Ke, additional, Jiang, Tao, additional, Joubert, Philippe, additional, Lunt, Alan C., additional, Ouwehand, Willem Hendrik, additional, Roberts, David J., additional, Timens, Wim, additional, van den Berge, Maarten, additional, Watkins, Nicholas A., additional, Battle, Alexis, additional, Butterworth, Adam S., additional, Danesh, John, additional, Di Angelantonio, Emanuele, additional, Engelhardt, Barbara E., additional, Peters, James E., additional, Sin, Don D., additional, and Burgess, Stephen, additional
Published: 2020
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239. Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals

Author: Folkersen, Lasse, primary, Gustafsson, Stefan, additional, Wang, Qin, additional, Hansen, Daniel Hvidberg, additional, Hedman, Åsa K., additional, Schork, Andrew, additional, Page, Karen, additional, Zhernakova, Daria V., additional, Wu, Yang, additional, Peters, James, additional, Eriksson, Niclas, additional, Bergen, Sarah E., additional, Boutin, Thibaud S., additional, Bretherick, Andrew D., additional, Enroth, Stefan, additional, Kalnapenkis, Anette, additional, Gådin, Jesper R., additional, Suur, Bianca E., additional, Chen, Yan, additional, Matic, Ljubica, additional, Gale, Jeremy D., additional, Lee, Julie, additional, Zhang, Weidong, additional, Quazi, Amira, additional, Ala-Korpela, Mika, additional, Choi, Seung Hoan, additional, Claringbould, Annique, additional, Danesh, John, additional, Davey Smith, George, additional, de Masi, Federico, additional, Elmståhl, Sölve, additional, Engström, Gunnar, additional, Fauman, Eric, additional, Fernandez, Celine, additional, Franke, Lude, additional, Franks, Paul W., additional, Giedraitis, Vilmantas, additional, Haley, Chris, additional, Hamsten, Anders, additional, Ingason, Andres, additional, Johansson, Åsa, additional, Joshi, Peter K., additional, Lind, Lars, additional, Lindgren, Cecilia M., additional, Lubitz, Steven, additional, Palmer, Tom, additional, Macdonald-Dunlop, Erin, additional, Magnusson, Martin, additional, Melander, Olle, additional, Michaelsson, Karl, additional, Morris, Andrew P., additional, Mägi, Reedik, additional, Nagle, Michael W., additional, Nilsson, Peter M., additional, Nilsson, Jan, additional, Orho-Melander, Marju, additional, Polasek, Ozren, additional, Prins, Bram, additional, Pålsson, Erik, additional, Qi, Ting, additional, Sjögren, Marketa, additional, Sundström, Johan, additional, Surendran, Praveen, additional, Võsa, Urmo, additional, Werge, Thomas, additional, Wernersson, Rasmus, additional, Westra, Harm-Jan, additional, Yang, Jian, additional, Zhernakova, Alexandra, additional, Ärnlöv, Johan, additional, Fu, Jingyuan, additional, Smith, J. Gustav, additional, Esko, Tõnu, additional, Hayward, Caroline, additional, Gyllensten, Ulf, additional, Landen, Mikael, additional, Siegbahn, Agneta, additional, Wilson, James F., additional, Wallentin, Lars, additional, Butterworth, Adam S., additional, Holmes, Michael V., additional, Ingelsson, Erik, additional, and Mälarstig, Anders, additional
Published: 2020
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240. Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases

Author: Zheng, Jie, primary, Haberland, Valeriia, additional, Baird, Denis, additional, Walker, Venexia, additional, Haycock, Philip C., additional, Hurle, Mark R., additional, Gutteridge, Alex, additional, Erola, Pau, additional, Liu, Yi, additional, Luo, Shan, additional, Robinson, Jamie, additional, Richardson, Tom G., additional, Staley, James R., additional, Elsworth, Benjamin, additional, Burgess, Stephen, additional, Sun, Benjamin B., additional, Danesh, John, additional, Runz, Heiko, additional, Maranville, Joseph C., additional, Martin, Hannah M., additional, Yarmolinsky, James, additional, Laurin, Charles, additional, Holmes, Michael V., additional, Liu, Jimmy Z., additional, Estrada, Karol, additional, Santos, Rita, additional, McCarthy, Linda, additional, Waterworth, Dawn, additional, Nelson, Matthew R., additional, Smith, George Davey, additional, Butterworth, Adam S., additional, Hemani, Gibran, additional, Scott, Robert A., additional, and Gaunt, Tom R., additional
Published: 2020
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241. Glycemic index, glycemic load, and risk of coronary heart disease: a pan-European cohort study

Author: Sieri, Sabina, primary, Agnoli, Claudia, additional, Grioni, Sara, additional, Weiderpass, Elisabete, additional, Mattiello, Amalia, additional, Sluijs, Ivonne, additional, Sanchez, Maria Jose, additional, Jakobsen, Marianne Uhre, additional, Sweeting, Michael, additional, van der Schouw, Yvonne T, additional, Nilsson, Lena Maria, additional, Wennberg, Patrik, additional, Katzke, Verena A, additional, Kühn, Tilman, additional, Overvad, Kim, additional, Tong, Tammy YN, additional, Conchi, Moreno-Iribas, additional, Quirós, José Ramón, additional, García-Torrecillas, Juan Manuel, additional, Mokoroa, Olatz, additional, Gómez, Jesús-Humberto, additional, Tjønneland, Anne, additional, Sonestedt, Emiliy, additional, Trichopoulou, Antonia, additional, Karakatsani, Anna, additional, Valanou, Elissavet, additional, Boer, Jolanda MA, additional, Verschuren, WM Monique, additional, Boutron-Ruault, Marie-Christine, additional, Fagherazzi, Guy, additional, Madika, Anne-Laure, additional, Bergmann, Manuela M, additional, Schulze, Matthias B, additional, Ferrari, Pietro, additional, Freisling, Heinz, additional, Lennon, Hannah, additional, Sacerdote, Carlotta, additional, Masala, Giovanna, additional, Tumino, Rosario, additional, Riboli, Elio, additional, Wareham, Nicholas J, additional, Danesh, John, additional, Forouhi, Nita G, additional, Butterworth, Adam S, additional, and Krogh, Vittorio, additional
Published: 2020
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242. Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

Author: Chen, Ming-Huei, primary, Raffield, Laura M., additional, Mousas, Abdou, additional, Sakaue, Saori, additional, Huffman, Jennifer E., additional, Moscati, Arden, additional, Trivedi, Bhavi, additional, Jiang, Tao, additional, Akbari, Parsa, additional, Vuckovic, Dragana, additional, Bao, Erik L., additional, Zhong, Xue, additional, Manansala, Regina, additional, Laplante, Véronique, additional, Chen, Minhui, additional, Lo, Ken Sin, additional, Qian, Huijun, additional, Lareau, Caleb A., additional, Beaudoin, Mélissa, additional, Hunt, Karen A., additional, Akiyama, Masato, additional, Bartz, Traci M., additional, Ben-Shlomo, Yoav, additional, Beswick, Andrew, additional, Bork-Jensen, Jette, additional, Bottinger, Erwin P., additional, Brody, Jennifer A., additional, van Rooij, Frank J.A., additional, Chitrala, Kumaraswamynaidu, additional, Cho, Kelly, additional, Choquet, Hélène, additional, Correa, Adolfo, additional, Danesh, John, additional, Di Angelantonio, Emanuele, additional, Dimou, Niki, additional, Ding, Jingzhong, additional, Elliott, Paul, additional, Esko, Tõnu, additional, Evans, Michele K., additional, Floyd, James S., additional, Broer, Linda, additional, Grarup, Niels, additional, Guo, Michael H., additional, Greinacher, Andreas, additional, Haessler, Jeff, additional, Hansen, Torben, additional, Howson, Joanna M.M., additional, Huang, Qin Qin, additional, Huang, Wei, additional, Jorgenson, Eric, additional, Kacprowski, Tim, additional, Kähönen, Mika, additional, Kamatani, Yoichiro, additional, Kanai, Masahiro, additional, Karthikeyan, Savita, additional, Koskeridis, Fotis, additional, Lange, Leslie A., additional, Lehtimäki, Terho, additional, Lerch, Markus M., additional, Linneberg, Allan, additional, Liu, Yongmei, additional, Lyytikäinen, Leo-Pekka, additional, Manichaikul, Ani, additional, Martin, Hilary C., additional, Matsuda, Koichi, additional, Mohlke, Karen L., additional, Mononen, Nina, additional, Murakami, Yoshinori, additional, Nadkarni, Girish N., additional, Nauck, Matthias, additional, Nikus, Kjell, additional, Ouwehand, Willem H., additional, Pankratz, Nathan, additional, Pedersen, Oluf, additional, Preuss, Michael, additional, Psaty, Bruce M., additional, Raitakari, Olli T., additional, Roberts, David J., additional, Rich, Stephen S., additional, Rodriguez, Benjamin A.T., additional, Rosen, Jonathan D., additional, Rotter, Jerome I., additional, Schubert, Petra, additional, Spracklen, Cassandra N., additional, Surendran, Praveen, additional, Tang, Hua, additional, Tardif, Jean-Claude, additional, Trembath, Richard C., additional, Ghanbari, Mohsen, additional, Völker, Uwe, additional, Völzke, Henry, additional, Watkins, Nicholas A., additional, Zonderman, Alan B., additional, Wilson, Peter W.F., additional, Li, Yun, additional, Butterworth, Adam S., additional, Gauchat, Jean-François, additional, Chiang, Charleston W.K., additional, Li, Bingshan, additional, Loos, Ruth J.F., additional, Astle, William J., additional, Evangelou, Evangelos, additional, van Heel, David A., additional, Sankaran, Vijay G., additional, Okada, Yukinori, additional, Soranzo, Nicole, additional, Johnson, Andrew D., additional, Reiner, Alexander P., additional, Auer, Paul L., additional, and Lettre, Guillaume, additional
Published: 2020
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243. The Polygenic and Monogenic Basis of Blood Traits and Diseases

Author: Vuckovic, Dragana, primary, Bao, Erik L., additional, Akbari, Parsa, additional, Lareau, Caleb A., additional, Mousas, Abdou, additional, Jiang, Tao, additional, Chen, Ming-Huei, additional, Raffield, Laura M., additional, Tardaguila, Manuel, additional, Huffman, Jennifer E., additional, Ritchie, Scott C., additional, Megy, Karyn, additional, Ponstingl, Hannes, additional, Penkett, Christopher J., additional, Albers, Patrick K., additional, Wigdor, Emilie M., additional, Sakaue, Saori, additional, Moscati, Arden, additional, Manansala, Regina, additional, Lo, Ken Sin, additional, Qian, Huijun, additional, Akiyama, Masato, additional, Bartz, Traci M., additional, Ben-Shlomo, Yoav, additional, Beswick, Andrew, additional, Bork-Jensen, Jette, additional, Bottinger, Erwin P., additional, Brody, Jennifer A., additional, van Rooij, Frank J.A., additional, Chitrala, Kumaraswamy N., additional, Wilson, Peter W.F., additional, Choquet, Hélène, additional, Danesh, John, additional, Di Angelantonio, Emanuele, additional, Dimou, Niki, additional, Ding, Jingzhong, additional, Elliott, Paul, additional, Esko, Tõnu, additional, Evans, Michele K., additional, Felix, Stephan B., additional, Floyd, James S., additional, Broer, Linda, additional, Grarup, Niels, additional, Guo, Michael H., additional, Guo, Qi, additional, Greinacher, Andreas, additional, Haessler, Jeff, additional, Hansen, Torben, additional, Howson, Joanna M.M., additional, Huang, Wei, additional, Jorgenson, Eric, additional, Kacprowski, Tim, additional, Kähönen, Mika, additional, Kamatani, Yoichiro, additional, Kanai, Masahiro, additional, Karthikeyan, Savita, additional, Koskeridis, Fotios, additional, Lange, Leslie A., additional, Lehtimäki, Terho, additional, Linneberg, Allan, additional, Liu, Yongmei, additional, Lyytikäinen, Leo-Pekka, additional, Manichaikul, Ani, additional, Matsuda, Koichi, additional, Mohlke, Karen L., additional, Mononen, Nina, additional, Murakami, Yoshinori, additional, Nadkarni, Girish N., additional, Nikus, Kjell, additional, Pankratz, Nathan, additional, Pedersen, Oluf, additional, Preuss, Michael, additional, Psaty, Bruce M., additional, Raitakari, Olli T., additional, Rich, Stephen S., additional, Rodriguez, Benjamin A.T., additional, Rosen, Jonathan D., additional, Rotter, Jerome I., additional, Schubert, Petra, additional, Spracklen, Cassandra N., additional, Surendran, Praveen, additional, Tang, Hua, additional, Tardif, Jean-Claude, additional, Ghanbari, Mohsen, additional, Völker, Uwe, additional, Völzke, Henry, additional, Watkins, Nicholas A., additional, Weiss, Stefan, additional, Cai, Na, additional, Kundu, Kousik, additional, Watt, Stephen B., additional, Walter, Klaudia, additional, Zonderman, Alan B., additional, Cho, Kelly, additional, Li, Yun, additional, Loos, Ruth J.F., additional, Knight, Julian C., additional, Georges, Michel, additional, Stegle, Oliver, additional, Evangelou, Evangelos, additional, Okada, Yukinori, additional, Roberts, David J., additional, Inouye, Michael, additional, Johnson, Andrew D., additional, Auer, Paul L., additional, Astle, William J., additional, Reiner, Alexander P., additional, Butterworth, Adam S., additional, Ouwehand, Willem H., additional, Lettre, Guillaume, additional, Sankaran, Vijay G., additional, and Soranzo, Nicole, additional
Published: 2020
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244. Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians

Author: Wang, Minxian, primary, Menon, Ramesh, additional, Mishra, Sanghamitra, additional, Patel, Aniruddh P., additional, Chaffin, Mark, additional, Tanneeru, Deepak, additional, Deshmukh, Manjari, additional, Mathew, Oshin, additional, Apte, Sanika, additional, Devanboo, Christina S., additional, Sundaram, Sumathi, additional, Lakshmipathy, Praveena, additional, Murugan, Sakthivel, additional, Sharma, Krishna Kumar, additional, Rajendran, Karthikeyan, additional, Santhosh, Sam, additional, Thachathodiyl, Rajesh, additional, Ahamed, Hisham, additional, Balegadde, Aniketh Vijay, additional, Alexander, Thomas, additional, Swaminathan, Krishnan, additional, Gupta, Rajeev, additional, Mullasari, Ajit S., additional, Sigamani, Alben, additional, Kanchi, Muralidhar, additional, Peterson, Andrew S., additional, Butterworth, Adam S., additional, Danesh, John, additional, Di Angelantonio, Emanuele, additional, Naheed, Aliya, additional, Inouye, Michael, additional, Chowdhury, Rajiv, additional, Vedam, Ramprasad L., additional, Kathiresan, Sekar, additional, Gupta, Ravi, additional, and Khera, Amit V., additional
Published: 2020
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245. Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries

Author: Zheng, Ju-Sheng, primary, Sharp, Stephen J, additional, Imamura, Fumiaki, additional, Chowdhury, Rajiv, additional, Gundersen, Thomas E, additional, Steur, Marinka, additional, Sluijs, Ivonne, additional, van der Schouw, Yvonne T, additional, Agudo, Antonio, additional, Aune, Dagfinn, additional, Barricarte, Aurelio, additional, Boeing, Heiner, additional, Chirlaque, María-Dolores, additional, Dorronsoro, Miren, additional, Freisling, Heinz, additional, El-Fatouhi, Douae, additional, Franks, Paul W, additional, Fagherazzi, Guy, additional, Grioni, Sara, additional, Gunter, Marc J, additional, Kyrø, Cecilie, additional, Katzke, Verena, additional, Kühn, Tilman, additional, Khaw, Kay-Tee, additional, Laouali, Nasser, additional, Masala, Giovanna, additional, Nilsson, Peter M, additional, Overvad, Kim, additional, Panico, Salvatore, additional, Papier, Keren, additional, Quirós, J Ramón, additional, Rolandsson, Olov, additional, Redondo-Sánchez, Daniel, additional, Ricceri, Fulvio, additional, Schulze, Matthias B, additional, Spijkerman, Annemieke M W, additional, Tjønneland, Anne, additional, Tong, Tammy Y N, additional, Tumino, Rosario, additional, Weiderpass, Elisabete, additional, Danesh, John, additional, Butterworth, Adam S, additional, Riboli, Elio, additional, Forouhi, Nita G, additional, and Wareham, Nicholas J, additional
Published: 2020
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246. Lipoprotein(a) in Alzheimer, Atherosclerotic, Cerebrovascular, Thrombotic, and Valvular Disease

Author: Larsson, Susanna C., primary, Gill, Dipender, additional, Mason, Amy M., additional, Jiang, Tao, additional, Bäck, Magnus, additional, Butterworth, Adam S., additional, and Burgess, Stephen, additional
Published: 2020
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247. Effects of adiposity on the human plasma proteome: Observational and Mendelian randomization estimates

Author: Goudswaard, Lucy J., primary, Bell, Joshua A., additional, Hughes, David A., additional, Corbin, Laura J., additional, Walter, Klaudia, additional, Smith, George Davey, additional, Soranzo, Nicole, additional, Danesh, John, additional, Di Angelantonio, Emanuele, additional, Ouwehand, Willem H., additional, Watkins, Nicholas A., additional, Roberts, David J., additional, Butterworth, Adam S., additional, Hers, Ingeborg, additional, and Timpson, Nicholas J., additional
Published: 2020
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248. ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study

Author: Gill, Dipender, primary, Arvanitis, Marios, additional, Carter, Paul, additional, Hernández Cordero, Ana I., additional, Jo, Brian, additional, Karhunen, Ville, additional, Larsson, Susanna C., additional, Li, Xuan, additional, Lockhart, Sam M., additional, Mason, Amy, additional, Pashos, Evanthia, additional, Saha, Ashis, additional, Tan, Vanessa Y., additional, Zuber, Verena, additional, Bossé, Yohan, additional, Fahle, Sarah, additional, Hao, Ke, additional, Jiang, Tao, additional, Joubert, Philippe, additional, Lunt, Alan C., additional, Ouwehand, Willem Hendrik, additional, Roberts, David J., additional, Timens, Wim, additional, van den Berge, Maarten, additional, Watkins, Nicholas A., additional, Battle, Alexis, additional, Butterworth, Adam S., additional, Danesh, John, additional, Engelhardt, Barbara E., additional, Peters, James E., additional, Sin, Don D., additional, and Burgess, Stephen, additional
Published: 2020
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249. Genomic evaluation of circulating proteins for drug target characterisation and precision medicine

Author: Folkersen, Lasse, primary, Gustafsson, Stefan, additional, Wang, Qin, additional, Hansen, Daniel Hvidberg, additional, Hedman, Åsa K, additional, Schork, Andrew, additional, Page, Karen, additional, Zhernakova, Daria V, additional, Wu, Yang, additional, Peters, James, additional, Ericsson, Niclas, additional, Bergen, Sarah E, additional, Boutin, Thibaud, additional, Bretherick, Andrew D, additional, Enroth, Stefan, additional, Kalnapenkis, Anettne, additional, Gådin, Jesper R, additional, Suur, Bianca, additional, Chen, Yan, additional, Matic, Ljubica, additional, Gale, Jeremy D, additional, Lee, Julie, additional, Zhang, Weidong, additional, Quazi, Amira, additional, Ala-Korpela, Mika, additional, Choi, Seung Hoan, additional, Claringbould, Annique, additional, Danesh, John, additional, Davey-Smith, George, additional, de Masi, Federico, additional, Elmståhl, Sölve, additional, Engström, Gunnar, additional, Fauman, Eric, additional, Fernandez, Celine, additional, Franke, Lude, additional, Franks, Paul, additional, Giedraitis, Vilmantas, additional, Haley, Chris, additional, Hamsten, Anders, additional, Ingason, Andres, additional, Johansson, Åsa, additional, Joshi, Peter K, additional, Lind, Lars, additional, Lindgren, Cecilia M., additional, Lubitz, Steven, additional, Palmer, Tom, additional, Macdonald-Dunlop, Erin, additional, Magnusson, Martin, additional, Melander, Olle, additional, Michaelsson, Karl, additional, Morris, Andrew P., additional, Mägi, Reedik, additional, Nagle, Michael, additional, Nilsson, Peter M, additional, Nilsson, Jan, additional, Orho-Melander, Marju, additional, Polasek, Ozren, additional, Prins, Bram, additional, Pålsson, Erik, additional, Qi, Ting, additional, Sjögren, Marketa, additional, Sundström, Johan, additional, Surendran, Praveen, additional, Võsa, Urmo, additional, Werge, Thomas, additional, Wernersson, Rasmus, additional, Westra, Harm-Jan, additional, Yang, Jian, additional, Zhernakova, Alexandra, additional, Ärnlöv, Johan, additional, Fu, Jingyuan, additional, Smith, Gustav, additional, Esko, Tonu, additional, Hayward, Caroline, additional, Gyllensten, Ulf, additional, Landen, Mikael, additional, Siegbahn, Agneta, additional, Wilson, Jim F, additional, Wallentin, Lars, additional, Butterworth, Adam S, additional, Holmes, Michael V, additional, Ingelsson, Erik, additional, and Mälarstig, Anders, additional
Published: 2020
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250. Correction: Lipoprotein signatures of cholesteryl ester transfer protein and HMG-CoA reductase inhibition

Author: Kettunen, Johannes, primary, Holmes, Michael V., additional, Allara, Elias, additional, Anufrieva, Olga, additional, Ohukainen, Pauli, additional, Oliver-Williams, Clare, additional, Wang, Qin, additional, Tillin, Therese, additional, Hughes, Alun D., additional, Kähönen, Mika, additional, Lehtimäki, Terho, additional, Viikari, Jorma, additional, Raitakari, Olli T., additional, Salomaa, Veikko, additional, Järvelin, Marjo-Riitta, additional, Perola, Markus, additional, Smith, George Davey, additional, Chaturvedi, Nish, additional, Danesh, John, additional, Di Angelantonio, Emanuele, additional, Butterworth, Adam S., additional, and Ala-Korpela, Mika, additional
Published: 2020
Full Text: View/download PDF

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