Search

Your search keyword '"Jennifer E Huffman"' showing total 9 results
Start Over Author "Jennifer E Huffman" Journal nature genetics
9 results on '"Jennifer E Huffman"'

1. Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease

Author

Saiju Pyarajan, Nicholas L. Smith, Julie Lynch, Sara Lindström, Michael G. Levin, Marijana Vujkovic, Charles Kooperberg, Danish Saleheen, Qing Shao, William E. Boden, Themistocles L. Assimes, Yan V. Sun, Peter D. Reaven, Sekar Kathiresan, Peter W.F. Wilson, Andrea T. Obi, Daniel J. Rader, Scott L. DuVall, David-Alexandre Trégouët, Jeffery Haessler, Pradeep Natarajan, Christopher Kabrhel, Krishna G. Aragam, Emma Busenkell, Renae Judy, Yunfeng Huang, Mary E. Haas, Peter K. Henke, J. Michael Gaziano, Jie Huang, Scott M. Damrauer, Philip S. Tsao, Kyung Min Lee, Donald R. Miller, John Concato, Kyong-Mi Chang, Jennifer E. Huffman, Mark Chaffin, Christopher J. O'Donnell, Alexander P. Reiner, Derek Klarin, Kelly Cho, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Genome-wide association study, Coronary Artery Disease, Disease, Bioinformatics, Mice, 0302 clinical medicine, Risk Factors, cardiovascular disease, 0303 health sciences, education.field_of_study, Venous Thromboembolism, Middle Aged, 3. Good health, Stroke, Prothrombin G20210A, Female, Population, Biology, Article, Peripheral Arterial Disease, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Plasminogen Activator Inhibitor 1, Genetics, medicine, Factor V Leiden, Animals, Humans, Genetic Predisposition to Disease, Vascular Diseases, cardiovascular diseases, education, Aged, 030304 developmental biology, business.industry, Case-control study, population genetics, equipment and supplies, medicine.disease, United Kingdom, Mice, Inbred C57BL, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic epidemiology, Genetic Loci, Case-Control Studies, genome-wide association studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Personalized medicine, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Venous thromboembolism (VTE) is a significant cause of mortality1, yet its genetic determinants remain incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank testing ~13 million DNA sequence variants for association with VTE (26,066 cases; 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 VTE cases and 167,295 controls. We identified 22 novel loci, bringing the total number of VTE-associated loci to 33 and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for VTE that identifies 5% of the population at equivalent incident VTE risk to carriers of the established F5 Leiden (p.R506Q) and prothrombin G20210A mutations. Our data provide new mechanistic insights into the genetic epidemiology of VTE and suggest a greater overlap among venous and arterial cardiovascular disease than previously suggested., Editorial summary Genome-wide analysis of venous thromboembolism identifies 22 new risk loci and facilitates construction of a polygenic risk score. Comparison to arterial vascular disease highlights shared pathophysiology and potential therapeutic strategies.

Published
2019

2. A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation

Author

Marijana, Vujkovic, Shweta, Ramdas, Kim M, Lorenz, Xiuqing, Guo, Rebecca, Darlay, Heather J, Cordell, Jing, He, Yevgeniy, Gindin, Chuhan, Chung, Robert P, Myers, Carolin V, Schneider, Joseph, Park, Kyung Min, Lee, Marina, Serper, Rotonya M, Carr, David E, Kaplan, Mary E, Haas, Matthew T, MacLean, Walter R, Witschey, Xiang, Zhu, Catherine, Tcheandjieu, Rachel L, Kember, Henry R, Kranzler, Anurag, Verma, Ayush, Giri, Derek M, Klarin, Yan V, Sun, Jie, Huang, Jennifer E, Huffman, Kate Townsend, Creasy, Nicholas J, Hand, Ching-Ti, Liu, Michelle T, Long, Jie, Yao, Matthew, Budoff, Jingyi, Tan, Xiaohui, Li, Henry J, Lin, Yii-Der Ida, Chen, Kent D, Taylor, Ruey-Kang, Chang, Ronald M, Krauss, Silvia, Vilarinho, Joseph, Brancale, Jonas B, Nielsen, Adam E, Locke, Marcus B, Jones, Niek, Verweij, Aris, Baras, K Rajender, Reddy, Brent A, Neuschwander-Tetri, Jeffrey B, Schwimmer, Arun J, Sanyal, Naga, Chalasani, Kathleen A, Ryan, Braxton D, Mitchell, Dipender, Gill, Andrew D, Wells, Elisabetta, Manduchi, Yedidya, Saiman, Nadim, Mahmud, Donald R, Miller, Peter D, Reaven, Lawrence S, Phillips, Sumitra, Muralidhar, Scott L, DuVall, Jennifer S, Lee, Themistocles L, Assimes, Saiju, Pyarajan, Kelly, Cho, Todd L, Edwards, Scott M, Damrauer, Peter W, Wilson, J Michael, Gaziano, Christopher J, O'Donnell, Amit V, Khera, Struan F A, Grant, Christopher D, Brown, Philip S, Tsao, Danish, Saleheen, Luca A, Lotta, Lisa, Bastarache, Quentin M, Anstee, Ann K, Daly, James B, Meigs, Jerome I, Rotter, Julie A, Lynch, Daniel J, Rader, Benjamin F, Voight, and Kyong-Mi, Chang

Subjects
Non-alcoholic Fatty Liver Disease, Genetics, Intracellular Signaling Peptides and Proteins, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Humans, Membrane Proteins, Alanine Transaminase, Lipase, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, Article, Genome-Wide Association Study
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P < 5 × 10(−8)). External replication in histology-defined NAFLD cohorts (7,397 cases and 56,785 controls) or radiologic imaging cohorts (n = 44,289) replicated 17 single-nucleotide polymorphisms (SNPs) (P < 6.5 × 10(−4)), of which 9 were new (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH and IFI30). Pleiotropy analysis showed that 61 of 77 multiancestry and all 17 replicated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD.

Published
2020

3. Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis

Author

Marijana, Vujkovic, Jacob M, Keaton, Julie A, Lynch, Donald R, Miller, Jin, Zhou, Catherine, Tcheandjieu, Jennifer E, Huffman, Themistocles L, Assimes, Kimberly, Lorenz, Xiang, Zhu, Austin T, Hilliard, Renae L, Judy, Jie, Huang, Kyung M, Lee, Derek, Klarin, Saiju, Pyarajan, John, Danesh, Olle, Melander, Asif, Rasheed, Nadeem H, Mallick, Shahid, Hameed, Irshad H, Qureshi, Muhammad Naeem, Afzal, Uzma, Malik, Anjum, Jalal, Shahid, Abbas, Xin, Sheng, Long, Gao, Klaus H, Kaestner, Katalin, Susztak, Yan V, Sun, Scott L, DuVall, Kelly, Cho, Jennifer S, Lee, J Michael, Gaziano, Lawrence S, Phillips, James B, Meigs, Peter D, Reaven, Peter W, Wilson, Todd L, Edwards, Daniel J, Rader, Scott M, Damrauer, Christopher J, O'Donnell, Philip S, Tsao, Kyong-Mi, Chang, Benjamin F, Voight, and Sumitra, Muralidhar

Subjects
Oncology, Male, medicine.medical_specialty, endocrine system diseases, Type 2 diabetes, Disease, Biology, Polymorphism, Single Nucleotide, Risk Assessment, Article, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Genetics, medicine, Genetic predisposition, Humans, Hypoglycemic Agents, Genetic Predisposition to Disease, Genetic Association Studies, 030304 developmental biology, Genetic association, 0303 health sciences, Chromosomes, Human, X, nutritional and metabolic diseases, medicine.disease, Black or African American, Europe, Diabetes Mellitus, Type 2, Meta-analysis, Medical genetics, Female, 030217 neurology & neurosurgery, Diabetic Angiopathies, Kidney disease
Abstract

We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score (PRS) was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD) and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including coronary heart disease (CHD), CKD, PAD and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes.

Published
2019

4. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author

Wenbo Tang, Stephen B. Kritchevsky, Ian P. Hall, Alexessander Couto Alves, Henry Völzke, Kim de Jong, Sina A. Gharib, Louise V. Wain, Adaikalavan Ramasamy, John M. Starr, Tatijana Zemunik, André G. Uitterlinden, Isabelle Pin, A. Bill Musk, Lina Zgaga, Ernst Omenaas, Mi Kyeong Lee, Nadia N. Hansel, Lewis J. Smith, Dana B. Hancock, Anne Viljanen, Anneli Pouta, Erik Melén, Nora Franceschini, Susan Campbell, Alicja R. Rudnicka, Melissa E. Garcia, Jemma B. Wilk, Igor Rudan, John Beilby, Fernando Rivadeneira, Gudny Eiriksdottir, Lenore J. Launer, Kristin M. Burkart, Ozren Polasek, Pieter S. Hiemstra, Regina Hampel, Jerome I. Rotter, Markku Heliövaara, Harald Grallert, Tim D. Spector, Andrew P. Morris, Jennifer E. Huffman, Pau Navarro, Jing Hua Zhao, Robert A. Scott, Bruno H. Stricker, Christopher Oldmeadow, Yeon-Mok Oh, Christian Gieger, Tove Fall, Caroline Hayward, Rodney J. Scott, Mika Kähönen, Vilmundur Gudnason, Guy Brusselle, Stefan Karrasch, Anne B. Newman, Alan James, Ida Surakka, Peter K. Joshi, R. Graham Barr, Fien Verhamme, Alexander Teumer, Ulf Gyllensten, Joohon Sung, Marjolein J. Peters, Ryan L. Minster, Kirsi H. Pietiläinen, Ian J. Deary, Lorna M. Lopez, Matthias Wjst, Myriam Fornage, Susan Redline, Wei Gao, Taina Rantanen, David J. Lederer, Gail Davies, Mary K. Wojczynski, Kari E. North, Beate Koch, Guo Li, George T. O'Connor, Blair H. Smith, Harry Campbell, Wendy B. White, Juha Pekkanen, Eva Albrecht, Sven Gläser, Joyce B. J. van Meurs, Stephen S. Rich, Wendy L. McArdle, Deborah Jarvis, Ani Manichaikul, Pirro G. Hysi, Christopher J Hammond, Erik Ingelsson, Albert V. Smith, John Attia, O. Dale Williams, Tamara B. Harris, Susan R. Heckbert, Josée Dupuis, Bruce M. Psaty, Åsa Johansson, Xin-Qun Wang, Samuli Ripatti, Woo Jin Kim, Patricia A. Cassano, H. Marike Boezen, David J. Porteous, Esteban G. Burchard, Kurt Lohman, Ivana Kolcic, Lies Lahousse, James F. Wilson, Dirkje S. Postma, Holly Trochet, Nicholas J. Wareham, Ana Viñuela, María Soler Artigas, Lars Lind, Jennie Hui, Bharat Thyagarajan, Judith M. Vonk, Marcy F. Petrini, Bonnie R. Joubert, Marjo-Riitta Järvelin, Xiangjun Gu, Claudia Flexeder, Generation Scotland, Sarah H. Wild, Nicholas D. Hastie, Thomas Lumley, Veronique Vitart, Laura R. Loehr, Joachim Heinrich, Yongmei Liu, Akshay Sood, Tess D. Pottinger, Alan F. Wright, Albert Hofman, Rajesh Kumar, Cisca Wijmenga, Elizabeth G. Holliday, Ian Sayers, David P. Strachan, Martin D. Tobin, Stefan Enroth, Thor Aspelund, Leslie A. Lange, Qing Duan, Daan W. Loth, Ken R. Bracke, Nathan C. Gaddis, David Couper, Stephanie J. London, Alanna C. Morrison, Holger Schulz, Jaakko Kaprio, Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Otorhinolaryngology and Head and Neck Surgery, Psychiatry, Epidemiology, Public Health, and Internal Medicine

Subjects
Spirometry, Lung Diseases, Vital capacity, Quantitative Trait Loci, Vital Capacity, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, DISEASE, Pulmonary function testing, Cohort Studies, FEV1/FVC ratio, Idiopathic pulmonary fibrosis, SDG 3 - Good Health and Well-being, Meta-Analysis as Topic, Forced Expiratory Volume, Databases, Genetic, Genetics, medicine, Humans, Restrictive lung disease, Lung volumes, Genetic Predisposition to Disease, lung, spriometry, SNP, gene, GENE-EXPRESSION, medicine.diagnostic_test, Genome, Human, HERITABILITY, HEALTHY TWIN, MORTALITY, ta3141, respiratory system, medicine.disease, Prognosis, 3. Good health, Respiratory Function Tests, respiratory tract diseases, FAMILY, LUNG-FUNCTION, Genetic Loci, Immunology, CELLS, IDIOPATHIC PULMONARY-FIBROSIS, TRAITS, Follow-Up Studies, Genome-Wide Association Study
Abstract

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P

Published
2014

5. Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Author

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

Subjects
Genetics & Heredity, 0301 basic medicine, Netherlands Twin Register (NTR), Science & Technology, computer.internet_protocol, Million Veteran Program, Genome-wide association study, Computational biology, 06 Biological Sciences, Biology, Genetic analysis, 03 medical and health sciences, 030104 developmental biology, Genetics, Genome informatics, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Life Sciences & Biomedicine, computer, 11 Medical and Health Sciences, XML, Developmental Biology
Abstract

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

Published
2018

6. Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Author

Arthur W. Musk, Ernst Omenaas, Dana B. Hancock, Jennie Hui, John W. Holloway, Nora Franceschini, Alan F. Wright, Ma'en Obeidat, Judith M. Vonk, Norman Klopp, Shah Ebrahim, R. Graham Barr, Jerome I. Rotter, Albert Hofman, Jennifer E. Huffman, Kirsi H. Pietiläinen, John Beilby, Bruno H. Ch. Stricker, Xiangjun Gu, Fernando Rivadeneira, James F. Wilson, Fredrik Nyberg, Peter D. Sly, María Soler Artigas, Bonnie R. Joubert, Marjo-Riitta Järvelin, Medea Imboden, Veronique Vitart, Albert V. Smith, Ida Surakka, C.M. Jackson, Susan R. Heckbert, Avan Aihie Sayer, Craig E. Pennell, Matthias Wjst, Ivana Kolcic, Cyrus Cooper, Wei Ang, Ian Sayers, John Britton, George T. O'Connor, Patrick G. Holt, Anna-Liisa Hartikainen, Adaikalavan Ramasamy, Jing Hua Zhao, Jonathan Marchini, Bernd Meibohm, Laura R. Loehr, Mark Eijgelsheim, David Couper, Massimo Mangino, Santosh Dahgam, Vilmundur Gudnason, David P. Strachan, Martin D. Tobin, Rebecca Hardy, Nicole Probst-Hensch, Stephen B. Kritchevsky, George Davey Smith, Tatijana Zemunik, Toby Johnson, Samuli Ripatti, Georg Homuth, Debbie A Lawlor, Thor Aspelund, Henry Völzke, John M. Starr, Aroon D. Hingorani, Khalid A. Al Balushi, Ivan Curjuric, John Henderson, Diana Kuh, Ruth J. F. Loos, Joachim Heinrich, Ozren Polasek, Yongmei Liu, Dirkje S. Postma, Raquel Granell, Akshay Sood, Kari E. North, Beate Koch, Christian Gieger, Tamara B. Harris, Anneli Pouta, David J. Porteous, Daan W. Loth, Sarah H. Wild, Gudny Eiriksdottir, Mladen Boban, Markku Heliövaara, Jonas Brisman, Mika Kähönen, Eva Albrecht, Pirro G. Hysi, Paul Elliott, Stephanie J. London, Guy Brusselle, Myriam Fornage, Thierry Rochat, Kurt Lohman, Ani Manichaikul, David M. Evans, Florian Kronenberg, Caroline Hayward, Harry Campbell, Tricia M. McKeever, So-Youn Shin, Deborah Jarvis, Alanna C. Morrison, Nicole M. Warrington, Holger Schulz, Karen A. Jameson, Stefan Karrasch, Cisca Wijmenga, Richard W Morris, Gauti Kjartan Gislason, Lina Zgaga, Ivica Grković, Alan James, Amanda P. Henry, O. Dale Williams, Jaakko Kaprio, Gemma Cadby, Susan M. Ring, Peter H. Whincup, Thomas Lumley, Nicholas J. Wareham, Lorna M. Lopez, John L. Hankinson, Christopher J Hammond, André G. Uitterlinden, Isabelle Pin, Shona M. Kerr, Alicja R. Rudnicka, Ian J. Deary, Taina Rantanen, Sven Gläser, Wendy L. McArdle, Andrew Wong, Ins Barroso, Lenore J. Launer, S. Goya Wannamethee, Wenbo Tang, Ian P. Hall, Sina A. Gharib, Louise V. Wain, Vesna Boraska, John D Blakey, H.-Erich Wichmann, Anna-Carin Olin, Patricia A. Cassano, H. Marike Boezen, Stipan Janković, Igor Rudan, Andrew D. Morris, Jason Z. Liu, Sarah E. Harris, Clyde Francks, Michael Hunter, Kristin D. Marciante, Stephen S. Rich, Darya Gaysina, Bruce M. Psaty, Melinda C. Aldrich, Melissa E. Garcia, Jemma B. Wilk, Tim D. Spector, Lyle J. Palmer, Guangju Zhai, Epidemiology, Internal Medicine, Public Health, Medical Research Council (MRC), The International Lung Cancer Consortium, Giant consortium, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Oncology, Vital capacity, PROTEIN, Genome-wide association study, BLOOD-PRESSURE, VARIANTS, Pulmonary function testing, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Epidemiology, IMPUTATION, Child, 11 Medical and Health Sciences, POPULATION, Genetics & Heredity, RISK, 0303 health sciences, education.field_of_study, WOMEN, GENETIC-VARIATION, 3. Good health, Respiratory Function Tests, medicine.anatomical_structure, Medical genetics, Life Sciences & Biomedicine, EXPRESSION, medicine.medical_specialty, MECOM, Population, European Continental Ancestry Group, Biology, OBSTRUCTIVE PULMONARY-DISEASE, Article, White People, 03 medical and health sciences, Internal medicine, Genetics, medicine, Humans, education, METAANALYSIS, POLYMORPHISMS, 030304 developmental biology, Lung, Science & Technology, MORTALITY, GIANT consortium, International Lung Cancer Consortium, 06 Biological Sciences, 030228 respiratory system, Immunology, lung, gene, gwas, Genome-Wide Association Study, Developmental Biology
Abstract

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

Published
2011

7. Meta-analysis and imputation refines the association of 15q25 with smoking quantity

Author

Mark J. Caulfield, Paul Scheet, Ruth J. F. Loos, Ozren Polasek, Vincent Mooser, Michael Wittig, Stephen E. Epstein, James F. Wilson, Gonçalo R. Abecasis, Jennifer E. Huffman, Augusto D. Pichard, Mary Susan Burnett, Rajesh Rawal, Federica Tozzi, Nilesh J. Samani, Hans J. Grabe, Robert L. Wilensky, Miles Parkes, Jing Hua Zhao, Jaspal S. Kooner, Daniel J. Rader, Wade H. Berrettini, Per Bakke, Robert W. Mahley, Astrid Petersmann, Alan F. Wright, Kenneth M. Kent, Lowell F. Satler, Alistair S. Hall, Xin Yuan, Hakon Hakonarson, Henry Völzke, Peter Vollenweider, Xiangjun Xiao, John B. Vincent, Joseph M. Lindsay, Scott M. Grundy, Christopher G. Mathew, Caroline Hayward, Susan Campbell, John R. Thompson, Alexander Teumer, Ins Barroso, David Schlessinger, Jack Satsangi, Benjamin J. Wright, Carl A. Anderson, Fabio Busonero, James L. Kennedy, Harry Campbell, Dan Rujescu, Anne Barton, H.-Erich Wichmann, Philip J. Barter, Veronique Vitart, Antonio Terracciano, Ruth McPherson, S. Horstmann, Anna F. Dominiczak, Martin Preisig, Susanne Lucae, David St Clair, Lina Zgaga, Jane Worthington, Joseph M. Devaney, Wendy Thomson, Anne Farmer, Antero Kesäniemi, Ulrich John, Tariq Ahmad, William H. Matthai, Jason Z. Liu, Muredach P. Reilly, Ivana Kolcic, Igor Rudan, Norbert Dahmen, Martin Farrall, Anthony J. Balmforth, Nicholas J. Wareham, Steve Eyre, T. Brueckl, Kay-Tee Khaw, Liming Qu, Christopher W. Knouff, Sarah H. Wild, Patricia B. Munroe, Claudia Lamina, Dawn M. Waterworth, John Strauss, John C. Chambers, Marcus Ising, Richard O. Day, Amund Gulsvik, Gérard Waeber, Arne Schäfer, Andre Franke, Clyde Francks, Pierandrea Muglia, Mingyao Li, Peter McGuffin, Keith Matthews, Manuela Uda, Sreekumar G. Pillai, Jonathan Marchini, Lefkos T. Middleton, Ron Waksman, and Wellcome Trust Case Control Consortium

Subjects
Genetics, 0303 health sciences, education.field_of_study, Population, Single-nucleotide polymorphism, Genome-wide association study, Locus (genetics), Biology, Article, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Genome-Wide Association, Nicotine Dependence, Lung-Cancer, Susceptibility Locus, Risk-Factors, Disease, Genes, SNPS, Colaus Study, SNP, 1000 Genomes Project, Allele, education, 030217 neurology & neurosurgery, Imputation (genetics), genome-wide association study, smoking initiation, smoking quantity, 030304 developmental biology
Abstract

Smoking is a leading global cause of disease and mortality(1). We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

Published
2010
Full Text
View/download PDF

8. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

Author

Lynne J. Hocking, Caterina Barbieri, Jenny Chang-Claude, David Karasik, Dieter Flesch-Janys, James F. Wilson, Mark S. Goldberg, Henry Voelzke, Archie Campbell, Stig E. Bojesen, David R. Weir, Ailith Pirie, Megan L. Grove, Melissa Wellons, Georg Homuth, Corrado Masciullo, Jennifer A. Brody, Hermann Brenner, Paolo Gasparini, Andrew D. Johnson, Patrick Neven, Graham G. Giles, Peter Kraft, André G. Uitterlinden, Wei Zheng, Alkes L. Price, Anja Rudolph, Arto Mannermaa, Nicholas G. Martin, Christopher A. Haiman, Massimo Mangino, Melissa C. Southey, Daniela Ruggiero, Toshiko Tanaka, Kathryn L. Lunetta, Julie E. Buring, John R. B. Perry, Robert Winqvist, Laufey Tryggvadottir, Angela Cox, Serena Sanna, Nicola Pirastu, Anna Jakubowska, Paul D.P. Pharoah, David J. Porteous, Dragana Vuckovic, Andrea D. Coviello, Giorgia Girotto, Sara Lindstroem, Patrick Sulem, Astrid Petersmann, Xin Li, Maartje J. Hooning, Lili Milani, Sven Bergmann, Marek Zygmunt, Javier Benitez, Vilmundur Gudnason, Fernando Rivadeneira, Volker Arndt, Marina Ciullo, Caroline Hayward, Sheila Ulivi, Janet E. Olson, Hoda Anton-Culver, Maria Kabisch, Sara Margolin, Vessela N. Kristensen, Patrick F. McArdle, Tanguy Corre, Nora Franceschini, Veli-Matti Kosma, Hiltrud Brauch, Roger L. Milne, Eric Boerwinkle, Matthias W. Beckmann, Charles Kooperberg, Qin Wang, Jessica D. Faul, Stephen J. Chanock, Alexander Teumer, Mark O. Goodarzi, Unnur Thorsteinsdottir, R Maegi, Paul M. Ridker, Antonis C. Antoniou, Ozren Polasek, Daniel F. Gudbjartsson, Barbara McKnight, Melissa E. Garcia, Manjeet K. Bolla, Alanna C. Morrison, Paolo Radice, Xiuqing Guo, Lude L. Franke, Michela Traglia, Marjanka K. Schmidt, Heli Nevanlinna, Teresa Nutile, Cinzia Sala, Pascal Guénel, Jennifer E. Huffman, Stephen T. Turner, Anna Murray, Carl Blomqvist, Margaux F. Keller, Samuel E. Jones, Montserrat Garcia-Closas, Ivana Kolcic, Anne B. Newman, Jan Lubinski, Albert Hofman, Isabel dos-Santos-Silva, Hilary K. Finucane, Anne Lise Børresen-Dale, Alexander P. Reiner, Tim D. Spector, Gonneke Willemsen, John D. Eicher, Douglas F. Easton, Claudia Langenberg, Anthony J. Swerdlow, Natalia Bogdanova, Alison M. Dunning, Giorgio Pistis, Tõnu Esko, Behrooz Z. Alizadeh, Martina Mueller-Nurasyid, Eleonora Porcu, Laura M. Yerges-Armstrong, Leslie J. Raffel, Laura Crisponi, Gonçalo R. Abecasis, Jerome I. Rotter, Yii-Der Ida Chen, Antonietta Robino, Katri Pylkaes, Ken K. Ong, Thibaud Boutin, Elinor J. Sawyer, Daniel I. Chasman, Brian E. Henderson, Frank B. Hu, Leslie Bernstein, Drakoulis Yannoukakos, Tamara B. Harris, Dorret I. Boomsma, Katherine S. Ruth, Jie Yao, Keith Humphreys, Jennifer A. Smith, Elisabeth Altmaier, Ulrike Peters, Doris Stoeckl, Eva Albrecht, Tatijana Zemunik, Jenny A. Visser, Minouk J. Schoemaker, Diego Vozzi, Thilo Doerk, J. Ross Chapman, Irene L. Andrulis, Joanne M. Murabito, Alan F. Wright, Lisette Stolk, Jonathan Marten, Alice M. Arnold, Paolo Peterlongo, Harry Campbell, Natalia Pervjakova, Jingmei Li, Jennifer Kriebel, Alicia Beeghly-Fadiel, Immaculata De Vivo, Jouke-Jan Hottenga, Kari Stefansson, Cornelia M. van Duijn, Brendan Bulik-Sullivan, Evelin Mihailov, Chunyan He, Joe Dennis, Nicholas J. Wareham, Yongmei Liu, Sharon L.R. Kardia, Lynda M. Rose, Felix R. Day, Georgia Chenevix-Trench, Albert V. Smith, David J. Hunter, Sandosh Padmanabhan, Christian Gieger, Konstantin Strauch, Igor Rudan, Jacques Simard, Jian'an Luan, Robert A. Scott, Kyriaki Michailidou, Bruce M. Psaty, Per Hall, Suzette J. Bielinski, Rita K. Schmutzler, Julian Peto, Ellen W. Demerath, Ursula M. Schick, Rossella Sorice, Wei Zhao, Børge G. Nordestgaard, Andres Metspalu, Jonine D. Figueroa, Julia A. Knight, Barbara Burwinkel, Thomas Bruening, Judith Manz, Anna González-Neira, Ilaria Gandin, Ian Tomlinson, Thérèse Truong, Kent D. Taylor, Amanda E. Toland, Deborah J. Thompson, Alfons Meindl, Caroline M. Seynaeve, Benjamin M. Neale, Fergus J. Couch, Mike A. Nalls, Ute Hamann, Kamila Czene, John L. Hopper, Bruce H. R. Wolffenbuttel, Grant W. Montgomery, Hatef Darabi, Daniela Toniolo, Jinyan Huang, Peter Devilee, Cathy E. Elks, David Schlessinger, Luigi Ferrucci, Frank Schmidt, Peter A. Fasching, Diether Lambrechts, Najaf Amin, Day, Felix R, Ruth, Katherine S, Thompson, Deborah J, Lunetta, Kathryn L, Pervjakova, Natalia, Chasman, Daniel I, Stolk, Lisette, Finucane, Hilary K, Sulem, Patrick, Bulik Sullivan, Brendan, Esko, Tõnu, Johnson, Andrew D, Elks, Cathy E, Franceschini, Nora, He, Chunyan, Altmaier, Elisabeth, Brody, Jennifer A, Franke, Lude L, Huffman, Jennifer E, Keller, Margaux F, Mcardle, Patrick F, Nutile, Teresa, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M, Schick, Ursula M, Smith, Jennifer A, Teumer, Alexander, Traglia, Michela, Vuckovic, Dragana, Yao, Jie, Zhao, Wei, Albrecht, Eva, Amin, Najaf, Corre, Tanguy, Hottenga, Jouke Jan, Mangino, Massimo, Smith, Albert V, Tanaka, Toshiko, Abecasis, Gonçalo R, Andrulis, Irene L, Anton Culver, Hoda, Antoniou, Antonis C, Arndt, Volker, Arnold, Alice M, Barbieri, CATERINA MARIA, Beckmann, Matthias W, Beeghly Fadiel, Alicia, Benitez, Javier, Bernstein, Leslie, Bielinski, Suzette J, Blomqvist, Carl, Boerwinkle, Eric, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Borresen Dale, Anne Lise, Boutin, Thibaud S, Brauch, Hiltrud, Brenner, Hermann, Brüning, Thoma, Burwinkel, Barbara, Campbell, Archie, Campbell, Harry, Chanock, Stephen J, Chapman, J. Ro, Chen, Yii Der Ida, Chenevix Trench, Georgia, Couch, Fergus J, Coviello, Andrea D, Cox, Angela, Czene, Kamila, Darabi, Hatef, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Devilee, Peter, Dörk, Thilo, Dos Santos Silva, Isabel, Dunning, Alison M, Eicher, John D, Fasching, Peter A, Faul, Jessica D, Figueroa, Jonine, Flesch Janys, Dieter, Gandin, Ilaria, Garcia, Melissa E, García Closas, Montserrat, Giles, Graham G, Girotto, Giorgia, Goldberg, Mark S, González Neira, Anna, Goodarzi, Mark O, Grove, Megan L, Gudbjartsson, Daniel F, Guénel, Pascal, Guo, Xiuqing, Haiman, Christopher A, Hall, Per, Hamann, Ute, Henderson, Brian E, Hocking, Lynne J, Hofman, Albert, Homuth, Georg, Hooning, Maartje J, Hopper, John L, Hu, Frank B, Huang, Jinyan, Humphreys, Keith, Hunter, David J, Jakubowska, Anna, Jones, Samuel E, Kabisch, Maria, Karasik, David, Knight, Julia A, Kolcic, Ivana, Kooperberg, Charle, Kosma, Veli Matti, Kriebel, Jennifer, Kristensen, Vessela, Lambrechts, Diether, Langenberg, Claudia, Li, Jingmei, Li, Xin, Lindström, Sara, Liu, Yongmei, Luan, Jian'An, Lubinski, Jan, Mägi, Reedik, Mannermaa, Arto, Manz, Judith, Margolin, Sara, Marten, Jonathan, Martin, Nicholas G, Masciullo, Corrado, Meindl, Alfon, Michailidou, Kyriaki, Mihailov, Evelin, Milani, Lili, Milne, Roger L, Müller Nurasyid, Martina, Nalls, Michael, Neale, Benjamin M, Nevanlinna, Heli, Neven, Patrick, Newman, Anne B, Nordestgaard, Børge G, Olson, Janet E, Padmanabhan, Sandosh, Peterlongo, Paolo, Peters, Ulrike, Petersmann, Astrid, Peto, Julian, Pharoah, Paul D. P, Pirastu, Nicola, Pirie, Ailith, Pistis, Giorgio, Polasek, Ozren, Porteous, David, Psaty, Bruce M, Pylkäs, Katri, Radice, Paolo, Raffel, Leslie J, Rivadeneira, Fernando, Rudan, Igor, Rudolph, Anja, Ruggiero, Daniela, Sala, Cinzia F, Sanna, Serena, Sawyer, Elinor J, Schlessinger, David, Schmidt, Marjanka K, Schmidt, Frank, Schmutzler, Rita K, Schoemaker, Minouk J, Scott, Robert A, Seynaeve, Caroline M, Simard, Jacque, Sorice, Rossella, Southey, Melissa C, Stöckl, Dori, Strauch, Konstantin, Swerdlow, Anthony, Taylor, Kent D, Thorsteinsdottir, Unnur, Toland, Amanda E, Tomlinson, Ian, Truong, Thérèse, Tryggvadottir, Laufey, Turner, Stephen T, Vozzi, Diego, Wang, Qin, Wellons, Melissa, Willemsen, Gonneke, Wilson, James F, Winqvist, Robert, Wolffenbuttel, Bruce B. H. R, Wright, Alan F, Yannoukakos, Drakouli, Zemunik, Tatijana, Zheng, Wei, Zygmunt, Marek, Bergmann, Sven, Boomsma, Dorret I, Buring, Julie E, Ferrucci, Luigi, Montgomery, Grant W, Gudnason, Vilmundur, Spector, Tim D, van Duijn, Cornelia M, Alizadeh, Behrooz Z, Ciullo, Marina, Crisponi, Laura, Easton, Douglas F, Gasparini, Paolo, Gieger, Christian, Harris, Tamara B, Hayward, Caroline, Kardia, Sharon L. R, Kraft, Peter, Mcknight, Barbara, Metspalu, Andre, Morrison, Alanna C, Reiner, Alex P, Ridker, Paul M, Rotter, Jerome I, Toniolo, Daniela, Uitterlinden, André G, Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J, Weir, David R, Yerges Armstrong, Laura M, Price, Alkes L, Stefansson, Kari, Visser, Jenny A, Ong, Ken K, Chang Claude, Jenny, Murabito, Joanne M, Perry, John R. B, Murray, Anna, Internal Medicine, Epidemiology, Medical Oncology, Clinical Genetics, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, PRACTICAL Consortium, kConFab Investigators, AOCS Investigators, EPIC-InterAct Consortium, LifeLines Cohort Study, Generation, Scotland, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Life Course Epidemiology (LCE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)

Subjects
Netherlands Twin Register (NTR), Aging, DNA Repair, LOCI, Genome-wide association study, BLOOD-PRESSURE, Disease, CHROMOSOMAL INSTABILITY, Bioinformatics, HOMOLOGOUS RECOMBINATION, PREMATURE OVARIAN FAILURE, Genotype, BRCA2 MUTATION CARRIERS, WIDE ASSOCIATION, Gene Regulatory Networks, NATURAL MENOPAUSE, Genetics, education.field_of_study, menopause, DDR, BODY-MASS INDEX, CELL-TYPES, BRCA1 Protein, Reproduction, BRCA1-mediated DNA repair, Age Factors, Obstetrics and Gynecology, General Medicine, Genomics, Middle Aged, 3. Good health, Menopause, Phenotype, Female, medicine.symptom, Signal Transduction, Delayed puberty, Adult, DNA repair, Population, Hypothalamus, Single-nucleotide polymorphism, Breast Neoplasms, Biology, Lower risk, DDR, Article, Breast cancer, SDG 3 - Good Health and Well-being, Mendelian randomization, medicine, Humans, Genetic Predisposition to Disease, Allele, education, Genetic association, Models, Genetic, business.industry, Genetic Variation, medicine.disease, Aging/genetics, BRCA1 Protein/genetics, Breast Neoplasms/genetics, Gene Regulatory Networks/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study/methods, Genomics/methods, Hypothalamus/metabolism, Menopause/genetics, Reproduction/genetics, Signal Transduction/genetics, business, Genome-Wide Association Study
Abstract

Menopause timing has a major impact on infertility and risk of disease. Younger age at natural (nonsurgical) menopause (ANM) is associated with a higher risk of osteoporosis, cardiovascular disease, and type 2 diabetes and a lower risk of breast cancer. Late menopause is associated with a higher risk of breast cancer. It is well known that the age at which women go through menopause is partly determined by genes, but the underlying mechanisms are poorly understood. Genome-wide association studies have identified 18 common genetic variants associated with ANM. These variants explain less than 5% of the variation in ANM compared with the 21% explained by all common variants on genome-wide association study arrays. This genome-wide association study was the collaborative effort of researchers from 177 institutions worldwide. The study was designed to investigate genetic variants associated with timing of menopause among a population of approximately 70,000 women of European ancestry. A dual strategy was used to identify both common and, for the first time, low-frequency coding variants associated with ANM. The causal relationship between ANM and breast cancer was investigated using a Mendelian randomization approach. Combined analysis identified 1208 single-nucleotide polymorphisms (SNPs) of a total of approximately 2.6 million that reached the genome-wide significance threshold for association with ANM. Forty-four regions with common variants were identified; among these 44 loci were 2 rare low-frequency missense alleles of large effect. A majority of ANM SNPs were enriched in DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal relationship between delayed ANM and breast cancer risk; there was approximately 6% increase in risk per year; P = 3 × 10-14); increased risk with delayed menopause appeared to be mediated primarily by prolonged sex hormone exposure in a woman’s lifetime, not DDR mechanisms. This is the first study to confirm the link between early and late menopause and breast cancer risk using genetic information. Age at natural menopause genetic variants influence breast cancer risk primarily through variation in menopause timing. Although carrying higher numbers of ANM-increasing variants and enrichment in DDR genes are associated with a modest increase in breast cancer risk, the major mechanism for increased risk appears to be prolonged estrogen and/or progesterone exposure due to delayed menopause.

Published
2015

9. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Dragana Vuckovic, Mariaelisa Graff, M. Arfan Ikram, Marit E. Jørgensen, Lia E. Bang, Gerome Breen, Torben Jørgensen, Matthias Blüher, Ivan Brandslund, Hester M. den Ruijter, Ian Ford, Timo A. Lakka, Jennifer Wessel, J. Wouter Jukema, Adam S. Butterworth, Iris M. Heid, Xiuqing Guo, Shuai Wang, Paul L. Auer, Tamuno Alfred, Katja K.H. Aben, Inês Barroso, Gail Davies, Helen Griffiths, Heather M. Highland, Myriam Fornage, Claudia Langenberg, Daniel R. Witte, Ilaria Gandin, Kent D. Taylor, Patrick T. Ellinor, Matti Uusitupa, Laura M. Yerges-Armstrong, Fotios Drenos, Lars Wallentin, Joanna M. M. Howson, Jaakko Tuomilehto, Andrew D. Morris, Lawrence F. Bielak, Mengmeng Du, Andrew J. Lotery, Ailith Pirie, Francis S. Collins, Eva Rabing Brix Petersen, Carolina Medina-Gomez, Manuel A. Rivas, Maria Karaleftheri, Jan-Håkan Jansson, Peter Kovacs, Jaspal S. Kooner, Markku Laakso, Fredrik Karpe, Markus Perola, Anubha Mahajan, Heather M. Stringham, Rohit Varma, Alex W. Hewitt, Chris J. Packard, Andrew C. Heath, Claudia Schurmann, Nele Friedrich, David Lamparter, Vanisha Mistry, Renée de Mutsert, Unnur Thorsteinsdottir, Naveed Sattar, Jennifer E. Huffman, Dale R. Nyholt, Johanna Kuusisto, Angela L. Mazul, Hanieh Yaghootkar, George Dedoussis, Yadav Sapkota, Elizabeth K. Speliotes, Amanda J. Cox, Jane Gibson, Christian Theil Have, Penny Gordon-Larsen, Alisa K. Manning, Jaakko Kaprio, Sita H. Vermeulen, Stella Trompet, Yucheng Jia, Dennis O. Mook-Kanamori, Torben Hansen, Kathleen Stirrups, Jean Ferrières, Douglas F. Easton, Ruth J. F. Loos, Gerard Pasterkamp, John M. Starr, Tellervo Korhonen, Betina H. Thuesen, Olov Rolandsson, Veikko Salomaa, Eric B. Larson, Thomas F. Vogt, John Danesh, Honghuang Lin, Gaëlle Marenne, Timothy M. Frayling, Anette Varbo, Daniel I. Chasman, Aliki-Eleni Farmaki, Lorraine Southam, Martina Müller-Nurasyid, Katharine R. Owen, Paul Mitchell, Ching-Ti Liu, Massimiliano Cocca, Anette P. Gjesing, Charles Kooperberg, Rebecca S. Fine, Wei Gan, Amy J. Swift, Gerard Tromp, Krina T. Zondervan, Henrik Vestergaard, Katherine S. Ruth, Angela D'Eustacchio, Uwe Völker, Beverley Balkau, Hayato Tada, Ingrid B. Borecki, Xueling Sim, Gudmar Thorleifsson, Wei Zhou, Yiqin Wang, Eleftheria Zeggini, Cora E. Lewis, Michael Boehnke, Evangelos Evangelou, Gabriel Cuellar-Partida, Sven Bergmann, Tinca J. C. Polderman, Philippe Amouyel, Roberta McKean-Cowdin, Ellen W. Demerath, Marco Brumat, Kjell Nikus, Anneke I den Hollander, Stefan Gustafsson, Allan Linneberg, Peter T. Campbell, Weihua Zhang, Leslie A. Lange, Gina M. Peloso, Jonathan P. Bradfield, Cornelia M. van Duijn, Xiaowei Zhan, Marie-Pierre Dubé, Liang He, André G. Uitterlinden, Anne Tybjærg-Hansen, Yingchang Lu, Wei Zhao, Liang Sun, Yii-Der Ida Chen, Paul I. W. de Bakker, Børge G. Nordestgaard, Karina Meidtner, Carsten A. Böger, Lynne E. Wagenknecht, Eric Kim, Pang Yao, Olli T. Raitakari, Nanette R. Lee, René S. Kahn, Lili Milani, Tessel E. Galesloot, Jussi Hernesniemi, Valgerdur Steinthorsdottir, Jie Yao, Eulalia Catamo, Kerrin S. Small, Sara M. Willems, Marcelo P. Segura-Lepe, Cecilia M. Lindgren, Asif Rasheed, Gonçalo R. Abecasis, Adam E. Locke, Konstantin Strauch, Albert V. Smith, Anke R. Hammerschlag, Frida Renström, Zoltán Kutalik, Giovanni Veronesi, Paul M. Ridker, David J. Carey, Yao Hu, Jaana Lindström, John Andrew Pospisilik, Mike A. Nalls, Erik Ingelsson, Colin N. A. Palmer, Mary F. Feitosa, John R. B. Perry, Anne E. Justice, Ele Ferrannini, Shuang Feng, Helen R. Warren, David J. Roberts, Igor Rudan, Jeffrey R. O'Connel, Alison Pattie, Christopher P. Nelson, Lars Lind, Feijie Wang, Tamara B. Harris, Keng-Hung Lin, Jerome I. Rotter, Matthew A. Allison, Robin Young, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Stefan Johansson, Alexander P. Reiner, Jing Hua Zhao, Poorva Mudgal, Tim D. Spector, Paul W. Franks, Loes M. Olde Loohuis, Harvey D. White, Pirjo Komulainen, Michelle L. O'Donoghue, Todd L. Edwards, Ozren Polasek, Andrew R. Wood, Dermot F. Reilly, Myriam Rheinberger, Cramer Christensen, G. Kees Hovingh, Hidetoshi Kitajima, Kristin L. Young, Audrey Y. Chu, Megan L. Grove, Suthesh Sivapalaratnam, Lisa Bastarache, Martin den Heijer, Oddgeir L. Holmen, Vilmundur Gudnason, Sameer E. Al-Harthi, Dewan S. Alam, Robert E. Schoen, Jin Li, Sascha Fauser, Janie Corley, Paolo Gasparini, Niels Grarup, Guillaume Lettre, Thomas N. Person, Mark I. McCarthy, Joel N. Hirschhorn, Ying Wu, Pia R. Kamstrup, Nilesh J. Samani, Panos Deloukas, Ethan M. Lange, Helena Kuivaniemi, Mika Kähönen, Michiel L. Bots, Annette Peters, Peggy L. Peissig, Wayne Huey-Herng Sheu, Steven A. Lubitz, Stefania Cappellani, Mauno Vanhala, Andrew P. Morris, Struan F.A. Grant, Mark Walker, Trevor A. Mori, Jian'an Luan, Matthias B. Schulze, Josh C. Denny, Sarah E. Medland, Sander W. van der Laan, Maggie C.Y. Ng, Eric Boerwinkle, Tibor V. Varga, Øyvind Helgeland, Anke Tönjes, Jessica van Setten, James P. Cook, Patricia B. Munroe, Heiner Boeing, Robert A. Scott, Karen L. Mohlke, Leena Moilanen, Ayush Giri, Andrew J. Slater, Andrew T. Hattersley, Mark J. Caulfield, Tõnu Esko, Mark C. H. Groot, Nancy L. Heard-Costa, Narisu Narisu, Danish Saleheen, Valérie Turcot, Lambertus A. Kiemeney, Nicholas G. D. Masca, Ruifang Li-Gao, Jean-Claude Tardif, Xu Lin, Kathleen Mullan Harris, Antonietta Robino, Alison M. Dunning, Jonathan Tyrer, Audrey E. Hendricks, Linda Broer, Patricia A. Peyser, Jessica D. Faul, Jose C. Florez, Anne U. Jackson, Eirini Marouli, Jette Bork-Jensen, John C. Chambers, Jordi Corominas Galbany, Ruth Frikke-Schmidt, David S. Crosslin, Bratati Kahali, Stavroula Kanoni, Gorm B. Jensen, Nicholas J. Wareham, Paul Elliott, Tune H. Pers, James A. Perry, Tugce Karaderi, Matt J. Neville, Marianne Benn, Svati H. Shah, Mathias Gorski, Michael Stumvoll, David Ellinghaus, Amber A. Burt, Kari E. North, Jeffrey Haessler, Rajiv Chowdhury, Folkert W. Asselbergs, Marie Moitry, Aniruddh P. Patel, Pamela J. Schreiner, Frank Kee, Donald W. Bowden, Sune F. Nielsen, Oluf Pedersen, John D. Rioux, Rainer Rauramaa, Satu Männistö, Deborah J. Thompson, Cristen J. Willer, Andre Franke, Kari Kuulasmaa, Nienke van Leeuwen, Carmel Moore, Sharon L.R. Kardia, Neil R. Robertson, Sekar Kathiresan, Erin B. Ware, Dawn M. Waterworth, James G. Wilson, Sandosh Padmanabhan, Emmanouil Tsafantakis, Hakon Hakonarson, Dajiang J. Liu, Digna R. Velez Edwards, Artitaya Lophatananon, Craig E. Pennell, Gail P. Jarvik, Adelheid Lempradl, Anu Loukola, Joe Dennis, Hans-Jörgen Grabe, Oscar H. Franco, Yongmei Liu, I. Sadaf Farooqi, Hannu Puolijoki, Huaixing Li, Caroline Hayward, Rudolf Uher, Veronique Vitart, Murray H. Brilliant, Kari Stefansson, Alexander Teumer, Nicholette D. Palmer, Vilmantas Giedraitis, Roel A. Ophoff, Sailaja Vedantam, Emanuele Di Angelantonio, Ken S. Lo, Grant W. Montgomery, Paul L. Huang, Praveen Surendran, Terho Lehtimäki, Katherine E. Tansey, Li-An Lin, Pål R. Njølstad, Thomas W. Winkler, Ian J. Deary, Erwin P. Bottinger, Carol A. Wang, Biological Psychology, Complex Trait Genetics, and Amsterdam Neuroscience - Complex Trait Genetics

Subjects
0301 basic medicine, 2. Zero hunger, 0303 health sciences, ComputerSystemsOrganization_COMPUTERSYSTEMIMPLEMENTATION, Published Erratum, Computational biology, Biology, medicine.disease, Obesity, Genealogy, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, ddc:570, Genetics, medicine, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Biological sciences, Body mass index, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.

Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results