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Genetic Associations for Activated Partial Thromboplastin Time and Prothrombin Time, their Gene Expression Profiles, and Risk of Coronary Artery Disease

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AMERICAN JOURNAL OF HUMAN GENETICS 2012年第1期91卷 152-162页

作者： Tang, Weihong Schwienbacher, Christine Lopez, Lorna M. Ben-Shlomo, Yoav Oudot-Mellakh, Tiphaine Johnson, Andrew D. Samani, Nilesh J. Basu, Saonli Goegele, Martin Davies, Gail Lowe, Gordon D. O. Tregouet, David-Alexandre Tan, Adrian Pankow, James S. Tenesa, Albert Levy, Daniel Volpato, Claudia B. Rumley, Ann Gow, Alan J. Minelli, Cosetta Yarnell, John W. G. Porteous, David J. Starr, John M. Gallacher, John Boerwinkle, Eric Visscher, Peter M. Pramstaller, Peter P. Cushman, Mary Emilsson, Valur Plump, Andrew S. Matijevic, Nena Morange, Pierre-Emmanuel Deary, Ian J. Hicks, Andrew A. Folsom, Aaron R. Univ Minnesota Div Epidemiol & Community Hlth Minneapolis MN 55454 USA European Acad Bozen Bolzano EURAC Ctr Biomed I-39100 Bolzano Italy Univ Ferrara Dept Expt & Diagnost Med I-44121 Ferrara Italy Univ Edinburgh Ctr Cognit Ageing & Cognit Epidemiol Edinburgh EH8 9JZ Midlothian Scotland Univ Edinburgh Dept Psychol Edinburgh EH8 9JZ Midlothian Scotland Univ Bristol Sch Social & Community Med Bristol BS8 2PS Avon England Univ Paris 06 INSERM UMR S 937 Inst Cardiometab & Nutr ICAN F-75013 Paris France NHLBI Framingham Heart Study Framingham MA 01702 USA NHLBI Ctr Populat Studies Bethesda MD 20824 USA NHLBI Div Intramural Res Bethesda MD 20824 USA Univ Leicester Glenfield Hosp Dept Cardiovasc Sci Leicester LE3 9QP Leics England Leicester Cardiovasc Biomed Res Unit Glenfield Hosp Natl Inst Hlth Res Leicester LE3 9QP Leics England Univ Minnesota Div Biostat Minneapolis MN 55455 USA Univ Glasgow Inst Cardiovasc & Med Sci Glasgow G12 8TA Lanark Scotland Inst Genet & Mol Med Med Res Council MRC Human Genet Unit Edinburgh EH4 2XU Midlothian Scotland Univ Edinburgh Royal Dick Sch Vet Studies Roslin Inst Roslin EH25 9RG Midlothian Scotland Queens Univ Belfast Epidemiol Res Grp Belfast BT12 6BJ Antrim North Ireland Univ Edinburgh Med Genet Sect Edinburgh EH4 2XU Midlothian Scotland Univ Edinburgh Alzheimer Scotland Dementia Res Ctr Edinburgh EH8 9JZ Midlothian Scotland Cardiff Univ Sch Med Dept Primary Care & Publ Hlth Cardiff CF14 4XN S Glam Wales Univ Texas Hlth Sci Ctr Houston Ctr Human Genet Houston TX 77030 USA Univ Texas Hlth Sci Ctr Houston Human Genome Sequencing Ctr Houston TX 77030 USA Queensland Inst Med Res Brisbane Qld 4029 Australia Gen Cent Hosp Dept Neurol I-39100 Bolzano Italy Univ Lubeck Dept Neurol D-23538 Lubeck Germany Univ Vermont Dept Med Burlington VT 05405 USA Univ Vermont Dept Pathol Burlington VT 05405 USA Merck & Co Inc Mol Programming & Res Informat Rahway NJ 07065 USA Merck Res Lab Dept Cardiova

Activated partial thromboplastin time (aPTT) and prothrombin time (PT) are clinical tests commonly used to screen for coagulation-factor deficiencies. One genome-wide association study (GWAS) has been reported previously for aPTT, but no GWAS has been reported for PT. We conducted a GWAS and meta-analysis to identify genetic loci for aPTT and PT. The GWAS for aPTT was conducted in 9,240 individuals of European ancestry from the Atherosclerosis Risk in Communities (ARIC) study, and the GWAS for PT was conducted in 2,583 participants from the Genetic Study of Three Population Microisolates in South Tyrol (MICROS) and the Lothian Birth Cohorts (LBC) of 1921 and 1936. Replication was assessed in 1,041 to 3,467 individuals. For aPTT, previously reported associations with KNG1, HRG, F11, F12, and ABO were confirmed. A second independent association in ABO was identified and replicated (rs8176704, p = 4.26 x 10(-24)). Pooling the ARIC and replication data yielded two additional loci in F5 (rs6028, p = 3.22 x 10(-9)) and AGBL1 (rs2469184, p = 3.61 x 10(-8)). For PT, significant associations were identified and confirmed in F7 (rs561241, p = 3.71 x 10(-56)) and PROCR/EDEM2 (rs2295888, p = 5.25 x 10(-13)). Assessment of existing gene expression and coronary artery disease (CAD) databases identified associations of five of the GWAS loci with altered gene expression and two with CAD. In summary, eight genetic loci that account for similar to 29% of the variance in aPTT and two loci that account for similar to 14% of the variance in PT were detected and supported by functional data.

关键词： PARTIAL thromboplastin time PROTHROMBIN time GENE expression CORONARY heart disease -- Risk factors BLOOD coagulation HUMAN genome DNA replication

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Pivotal topline data from the phase 1/2 TRIDENT-1 trial of repotrectinib in patients with ROS1+advanced non-small cell lung cancer (NSCLC)

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EUROPEAN JOURNAL OF CANCER 2022年 174卷 S1-S2页

作者： Cho, B. C. Lin, J. Camidge, D. R. Velcheti, V. Solomon, B. Lu, S. Lee, K. H. Kim, S. W. Kao, S. Diadziuskzko, R. Beg, M. Nagasaka, M. Felip, E. Besse, B. Springfeld, C. Popat, S. Wolf, J. Trone, D. Stopatschinskaja, S. Drilon, A. Yonsei Univ Dept Internal Med Yonsei Canc Ctr Coll Med Seoul South Korea Harvard Med Sch Massachusetts Gen Hospital Hematol Oncol Boston MA 02115 USA Univ Colorado Med Oncol Denver Anschutz Med Campus Aurora CO USA NYU Dept Med NYU Perlmutter Canc Ctr Grossman Sch Med New York NY USA Peter MacCallum Canc Ctr Dept Med Oncol Melbourne Australia Shanghai Chest Hosp Dept Oncol Shanghai Peoples R China Chungbuk Natl Univ Hosp Dept Internal Med Cheongju South Korea Asan Med Ctr Dept Oncol Seoul South Korea Chris Obrien Lifehouse Dept Oncol Camperdown NSW Australia Med Univ Gdansk Dept Oncol & Radiotherapy Early Clin Trials Ctr Gdansk Poland UT SouthWestern Med Ctr Dept Oncol Dallas TX USA Univ Calif Irvine Hematol Oncol Sch Med Irvine CA USA Vall Hebron Univ Hosp Vall Hebron Inst Oncol VHIO Dept Oncol Barcelona Spain Univ Paris Saclay Canc Med Gustave Roussy Canc Ctr Villejuif France Univ Heidelberg Hosp Dept Med Oncol Natl Ctr Tumor Dis Heidelberg Germany Royal Marsden NHS Fdn Trust Dept Oncol London England Uniklin Koln Ctr Integrierte Onkol Dept Oncol Cologne Germany Turning Point Therapeut Inc Biostat & Programming San Diego CA USA Turning Point Therapeut Inc Clin Dev San Diego CA USA Weill Cornell Med Coll Early Drug Dev Serv Mem Sloan Kettering Canc Ctr New York NY USA

2LBA

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The Locommotion Study (MMY4001): A Prospective, Multinational Study of RealLife Current Standards of Care in Patients with Relapsed and/or Refractory Multiple Myeloma Who Received at Least 3 Prior Lines of Therapy Including PI, IMiD, and CD38 Monoclonal Antibody Treatment and Documented Disease Progression

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BLOOD 2019年 134卷 5549-5549页

作者： Delforge, Michel Moreau, Philippe Mateos, Maria-Victoria De Stefano, Valerio Weisel, Katja San-Miguel, Jesus Einsele, Hermann Facon, Thierry Boccadoro, Mario Goldschmidt, Hartmut Cavo, Michele Rosinol, Laura Kaiser, Martin F. Gay, Francesca Scheid, Christof Broyl, Annemiek Van De Donk, Niels W. C. J. Rodriguez, Paula Potamianou, Anna Sakabedoyan, Caline Strulev, Vadim Nesheiwat, Tonia Bergmans, Paul Rizvi, Syed Pilatowicz, Arkadiusz Sonneveld, Pieter Univ Hosp UZ Leuven Dept Hematol Leuven Belgium Univ Hosp Hotel Dieu Clin Hematol Nantes France Univ Hosp Salamanca Inst Canc Mol & Cellular Biol Salamanca Spain Univ Cattolica Ist Ematol Rome Italy Univ Med Ctr Hamburg Eppendorf Dept Med 2 Hamburg Germany Clin Univ Navarra Dept Hematol CIMA IDISNA Pamplona Spain Univ Klinikum Wurzburg Med Klin & Poliklin 2 Wurzburg Germany Hop Claude Huriez Hosp Huriez Serv Malad Sang Lille France AOU Citta Salute & Sci Torino Div Hematol 1 Dept Oncol Turin Italy Heidelberg Univ Heidelberg Germany Bologna Univ Seragnoli Inst Hematol Sch Med Bologna Italy Hosp Clin Barcelona Inst Hematol & Oncol Dept Hematol IDIBAPS Barcelona Spain Inst Canc Res London England Univ Torino Div Hematol Turin Italy Univ Cologne Dept Internal Med 1 Cologne Germany Univ Cologne Ctr Integrated Oncol Cologne Bonn Cologne Germany Erasmus MC Canc Inst Dept Hematol Rotterdam Netherlands Vrije Univ Amsterdam Amsterdam UMC Dept Hematol Canc Ctr Amsterdam Amsterdam Netherlands Clin Univ Navarra Pamplona Spain Janssen Cilag EMEA Med Affairs Neuss Germany Janssen Cilag EMEA Med Affairs Beirut Lebanon Janssen Pharmaceut NV EMEA Med Affairs Beerse Belgium Legend Biotech USA Piscataway NJ USA Janssen Cilag Biostat & Programming Breda Netherlands Janssen Cilag EMEA Med Affairs Operat Warsaw Poland Erasmus MC Canc Inst Rotterdam Netherlands

5549

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MaP NATURAL HISTORY STUDY: CLINICAL AND BIOMARKER FINDINGS IN METHYLMALONIC ACIDEMIA DUE TO MUT DEFICIENCY

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MOLECULAR GENETICS AND METABOLISM 2023年第3期138卷 84-84页

作者： Schiff, Manuel Schwahn, Bernd C. Chabrol, Brigitte Merritt, J. Lawrence, II Vockley, Jerry Vernon, Hilary Berry, Gerard T. Santra, Saikat Lee, Chung Koeberl, Dwight Li, Hong Burton, Barbara De las Heras, Javier Diaz, George Faria-Urbina, Mariana Luo, Junxiang Attarwala, Husain Sikirica, Vanja Liang, Min Guey, Lin T. Lukacs, Christine Martini, Paolo G. V. Glaser, Ruchira Carrillo, Nuria Hop Necker Enfants Malad Reference Ctr Inherited Metab Disorders Paris France St Marys Hosp Manchester Manchester Ctr Genom Med Manchester Lancs England Hop La Timone Pediat Marseille France Univ Washington Seattle Childrens Hosp Pediat Seattle WA USA Univ Pittsburgh Pediat Sch Med Pittsburgh PA USA Johns Hopkins Univ Dept Genet Med Sch Med Baltimore MD USA Boston Childrens Hosp Genet Boston MA USA Birmingham Childrens Hosp Pediat Inherited Metab Med Birmingham W Midlands England Lucile Packard Childrens Hosp Stanford Div Med Genet Dept Pediat Palo Alto CA USA Duke Univ Div Med Genet Dept Pediat Sch Med Durham NC USA Emory Univ Dept Human Genet & Pediat Sch Med Atlanta GA USA Childrens Healthcare Atlanta Atlanta GA USA Ann & Robert H Lurie Childrens Hosp Chicago Genet Birth Defects & Metab Chicago IL USA Hosp Univ Cruces Unidad Metab Vizcaya Spain Icahn Sch Med Mt Sinai Dept Genet & Genom Sci New York NY USA Moderna Inc Therapeut Cambridge MA USA Moderna Inc Biostat & Programming Cambridge MA USA Moderna Inc Pharmacometr & Clin Pharmacol Cambridge MA USA Moderna Inc Rare & Autoimmune Dis Cambridge MA USA Moderna Inc Pharmacometr Cambridge MA USA Moderna Inc R&ED Cambridge MA USA Moderna Inc XRV Cambridge MA USA Moderna Inc Res & Dev Cambridge MA USA Moderna Inc Therapeut & Oncol Cambridge MA USA Moderna Inc Rare Dis Cambridge MA USA

102

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Overall survival results from the phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma (METEOR)

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EUROPEAN JOURNAL OF CANCER 2017年 72卷 S187-S188页

作者： Schmidinger, M. Motzer, R. J. Powles, T. Escudier, B. Tannir, N. M. Mainwaring, P. N. Rini, B. I. Hammers, H. J. Donscov, F. Roth, B. Peltola, K. Lee, J. L. Heng, D. Y. C. Aftab, D. T. Hessel, C. Scheffold, C. Schwab, G. Pal, S. Hutson, T. E. Choueiri, T. K. Med Univ Wien Div Oncol Vienna Austria Mem Sloan Kettering Canc Ctr Dept Med Oncol 1275 York Ave New York NY 10021 USA St Bartholomews Hosp Expt Canc Med London England Inst Gustave Roussy Dept Med Oncol Kidney Canc Villejuif France Univ Texas MD Anderson Canc Ctr Dept Genitourinary Med Oncol Houston TX 77030 USA Mater Med Ctr Haematol Clin Australia Dept Med Oncol South Brisbane Australia Mater Med Ctr Oncol Clin Australia Dept Med Oncol South Brisbane Australia Cleveland Clin Fdn Dept Hematol & Oncol Main Campus Cleveland OH USA Univ Texas Southwestern Med Ctr Dallas Kidney Canc Program Dallas TX 75390 USA Aarhus Univ Hosp Dept Oncol Aarhus Denmark Washington Univ Sch Med St Louis Div Oncol St Louis MO USA Helsingin Yliopistollinen Keskussairaala Dept Oncol Helsinki Finland Asan Med Ctr Dept Oncol Seoul South Korea Alberta Hlth Serv Tom Baker Canc Ctr Calgary AB Canada Exelixis Inc Business Operat San Francisco CA USA Exelixis Inc Biostat & Clin Data Management & Stat Programming San Francisco CA USA Exelixis Inc Clin Res San Francisco CA USA Exelixis Inc Prod Dev & Med Affairs San Francisco CA USA City Hope Natl Med Ctr Kidney Canc Program Duarte CA USA Texas Oncol PA Dept Genitourinary Med Oncol Dallas TX USA Dana Farber Canc Inst Lank Ctr Genitourinary Oncol Boston MA 02115 USA

2117

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MaP NATURAL HISTORY STUDY: CLINICAL AND BIOMARKER FINDINGS IN PROPIONIC ACIDEMIA

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MOLECULAR GENETICS AND METABOLISM 2023年第3期138卷 85-85页

作者： Schwahn, Bernd C. Berry, Gerard T. Santra, Saikat Vernon, Hilary Li, Hong Merritt, Lawrence, II Schiff, Manuel Chabrol, Brigitte De las Heras, Javier Vockley, Jerry Lee, Chung Koeberl, Dwight Burton, Barbara Grunewald, Stephanie Morgan, Thomas Diaz, George Ficicioglu, Can Luo, Junxiang Attarwala, Husain Sikirica, Vanja Liang, Min Guey, Lin T. Lukacs, Christine Martini, Paolo G. V. Glaser, Ruchira Carrillo, Nuria St Marys Hosp Manchester Ctr Genom Med Manchester Lancs England Boston Childrens Hosp Genet Boston MA USA Birmingham Childrens Hosp Pediat Inherited Metab Med Birmingham W Midlands England Johns Hopkins Univ Hosp Dept Genet Med Baltimore MD 21287 USA Emory Univ Sch Med Dept Human Genet Atlanta GA USA Childrens Healthcare Atlanta Atlanta GA USA Univ Washington Seattle Childrens Hosp Pediat Seattle WA 98195 USA Hop Necker Enfants Malad Reference Ctr Inherited Metab Disorders Paris France Hop La Timone Pediat Marseille France Hosp Univ Cruces Unidad Metab Vizcaya Spain Univ Pittsburgh Pediat Sch Med Pittsburgh PA USA Lucile Packard Childrens Hosp Stanford Div Med Genet Dept Pediat Stanford CA USA Duke Univ Sch Med Dept Pediat Div Med Genet Durham NC USA Ann & Robert H Lurie Childrens Hosp Chicago Genet Birth Defects & Metab Chicago IL 60611 USA UCL Great Ormond St Hosp Children NIHR Biomed Res Ctr BRC Metab Unit London England Vanderbilt Univ Med Ctr Dept Pediat Nashville TN 37232 USA Icahn Sch Med Mt Sinai Dept Genet & Genom Sci New York NY 10029 USA Childrens Hosp Philadelphia Dept Pediat Philadelphia PA 19104 USA Moderna Inc Biostat & Programming Cambridge MA USA Moderna Inc Pharmacometr & Clin Pharmacol Cambridge MA USA Moderna Inc Rare & Autoimmune Dis Cambridge MA USA Moderna Inc Pharmacometr Cambridge MA USA Moderna Inc R&ED Cambridge MA USA Moderna Inc XRV Cambridge MA USA Moderna Inc Res & Dev Cambridge MA USA Moderna Inc Therapeut & Oncol Cambridge MA USA Moderna Inc Rare Dis Cambridge MA USA

103

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Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer

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ANNALS OF ONCOLOGY 2022年第12期33卷 1250-1268页

作者： Geyer, C. E., Jr. Garber, J. E. Gelber, R. D. Yothers, G. Taboada, M. Ross, L. Rastogi, P. Cui, K. Arahmani, A. Aktan, G. Armstrong, A. C. Arnedos, M. Balmana, J. Bergh, J. Bliss, J. Delaloge, S. Domchek, S. M. Eisen, A. Elsafy, F. Fein, L. E. Fielding, A. Ford, J. M. Friedman, S. Gelmon, K. A. Gianni, L. Gnant, M. Hollingsworth, S. J. Im, S-A Jager, A. Lakhani, S. R. Janni, W. Linderholm, B. Liu, T-W Loman, N. Korde, L. Loibl, S. Lucas, P. C. Marme, F. de Duenas, E. Martinez McConnell, R. Phillips, K-A Piccart, M. Rossi, G. Schmutzler, R. Senkus, E. Shao, Z. Sharma, P. Singer, C. F. Spanic, T. Stickeler, E. Toi, M. Traina, T. A. Viale, G. Zoppoli, G. Park, Y. H. Yerushalmi, R. Yang, H. Pang, D. Jung, K. H. Mailliez, A. Fan, Z. Tennevet, I Zhang, J. Nagy, T. Sonke, G. S. Sun, Q. Parton, M. Colleoni, M. A. Schmidt, M. Brufsky, A. M. Razaq, W. Kaufman, B. Cameron, D. Campbell, C. Tutt, A. N. J. Johannsson, O. Th NRG Oncol NSABP Fdn Pittsburgh PA USA UPMC Hillman Canc Ctr Dept Med Pittsburgh PA USA Harvard Med Sch Dana Farber Canc Inst Boston MA 02115 USA Harvard TH Chan Sch Publ Hlth Boston MA USA Frontier Sci Fdn Boston MA USA Univ Pittsburgh Dept Biostat Pittsburgh PA 15261 USA AstraZeneca Oncol Biometr Dept Macclesfield Cheshire England Frontier Sci Scotland Dept Data Management Kincraig Scotland AstraZeneca Dept Oncol R&D Gaithersburg MD USA Breast Int Grp Res Operat Dept Brussels Belgium Merck & Co Inc Global Oncol Clin Dev Rahway NJ 07065 USA Christie Hosp NHS Fdn Trust Dept Med Oncol Manchester Lancs England European Org Res & Treatment EORTC Brussels Belgium Inst Bergonie Dept Med Oncol Bordeaux France Vall dHebron Inst Oncol Med Oncol Dept Barcelona Spain Vall dHebron Univ Hosp Barcelona Spain Karolinska Inst Dept Oncol Pathol Swedish Breast Canc Grp Stockholm Sweden Karolinska Univ Hosp Breast Canc Ctr Stockholm Sweden Karolinska Comprehens Canc Ctr Stockholm Sweden Inst Canc Res Dept Clin Trials London England Inst Canc Res Stat Unit ICR CTSU London England Inst Gustave Roussy Dept Canc Med Paris France Unicanc Breast Grp Paris France Univ Penn Basser Ctr BRCA Abramson Canc Ctr Dept Med Philadelphia PA USA Univ Toronto Odette Canc Ctr Dept Med Toronto ON Canada Inst Oncol Rosario Dept Clin Res Santa Fe Argentina Stanford Univ Sch Med Dept Med Oncol Stanford CA 94305 USA Facing Our Risk Canc Empowered Tampa FL USA BC Canc Dept Med Oncol Vancouver BC Canada Int Breast Canc Study Grp Dept Oncol Bern Switzerland Osped Infermi AUSL Romagna Dept Med Oncol Rimini Italy Med Univ Vienna Comprehens Canc Ctr Vienna Austria AstraZeneca Dept Late Dev Oncol Cambridge England Seoul Natl Univ Seoul Natl Univ Hosp Coll Med Canc Res InstDept Internal Med Seoul South Korea Dutch Breast Canc Res Grp Dept Med Oncol Utrecht Netherlands Landsp Tali Univ Hosp Iceland Dept Med Oncol Iceland Breast Canc Grp Reykjavik Iceland

Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68;98.5% confidence interval (CI) 0.47-0.97;P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically

关键词： breast cancer BRCA1/2 PARP inhibition olaparib adjuvant therapy

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Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

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LANCET PUBLIC HEALTH 2022年第8期7卷 E657-E669页

作者： Peden, Amy E. Cullen, Patricia Francis, Kate Louise Moeller, Holger Peden, Margaret M. Ye, Pengpeng Tian, Maoyi Zou, Zhiyong Sawyer, Susan M. Aali, Amirali Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Mohsen Abdelmasseh, Michael Abdoun, Meriem Abd-Rabu, Rami Abdulah, Deldar Morad Abdurehman, Ame Mehadi Abebe, Getachew Abebe, Ayele Mamo Abedi, Aidin Abidi, Hassan Aboagye, Richard Gyan Ali, Hiwa Abubaker Abu-Gharbieh, Eman Adane, Denberu Eshetie Adane, Tigist Demssew Addo, Isaac Yeboah Adewole, Ololade Grace Adhikari, Sangeet Adnan, Mohammad Adnani, Qorinah Estiningtyas Sakilah Afolabi, Aanuoluwapo Adeyimika Bachelor Afzal, Saira Afzal, Muhammad Sohail Aghdam, Zahra Babaei Ahinkorah, Bright Opoku Ahmad, Araz Ramazan Ahmad, Tauseef Ahmad, Sajjad Ahmadi, Ali Ahmed, Haroon Ahmed, Muktar Beshir Ahmed, Ali Ahmed, Ayman Ahmed, Jivan Qasim Rashid, Tarik Ahmed Aithala, Janardhana P. Aji, Budi Akhlaghdoust, Meisam Alahdab, Fares Alanezi, Fahad Mashhour Alemayehu, Astawus Al Hamad, Hanadi Ali, Syed Shujait Ali, Liaqat Alimohamadi, Yousef Alipour, Vahid Aljunid, Syed Mohamed Almidani, Louay Almustanyir, Sami Altirkawi, Khalid A. Alvis-Zakzuk, Nelson J. Ameyaw, Edward Kwabena Amin, Tarek Tawfik Amir-Behghadami, Mehrdad Amiri, Sohrab Amiri, Hoda Anagaw, Tadele Fentabil Andrei, Tudorel Andrei, Catalina Liliana Anvari, Davood Anwar, Sumadi Lukman Anyasodor, Anayochukwu Edward Arabloo, Jalal Arab-Zozani, Morteza Arja, Asrat Arulappan, Judie Arumugam, Ashokan Aryannejad, Armin Asgary, Saeed Ashraf, Tahira Athari, Seyyed Shamsadin Atreya, Alok Attia, Sameh Aujayeb, Avinash Awedew, Atalel Fentahun Azadnajafabad, Sina Azangou-Khyavy, Mohammadreza Azari, Samad Jafari, Amirhossein Azari Azizi, Hosein Azzam, Ahmed Y. Badiye, Ashish D. Baghcheghi, Nayereh Bagherieh, Sara Baig, Atif Amin Bakkannavar, Shankar M. Balta, Asaminew Birhanu Banach, Maciej Banik, Palash Chandra Bansal, Hansi Bardhan, Mainak Barone-Adesi, Francesco Barrow, Amadou Bashiri, Azadeh Baskaran, Pritish Basu, Saurav Bayileyegn, Nebiyou Simegnew Bekel, Abebe Ayalew Bekele, UNSW Sydney Kensington NSW 2052 Australia Univ New South Wales Sch Publ Hlth & Community Med Sydney NSW Australia Univ New South Wales Populat Hlth Dept Sydney NSW Australia Univ New South Wales Sch Populat Hlth Sydney NSW Australia Univ New South Wales George Inst Global Hlth Sydney NSW Australia Univ New South Wales Ctr Social Res Hlth Sydney NSW Australia James Cook Univ Sch Publ Hlth Med & Vet Sci Townsville NSW Australia George Inst Global Hlth Global Womens Hlth Div Newtown NSW Australia George Inst Global Hlth Injury Div Newtown NSW Australia George Inst Global Hlth Dept Injury Newtown NSW Australia Murdoch Childrens Res Inst Ctr Adolescent Hlth Melbourne Vic Australia Imperial Coll London Sch Publ Hlth London England Imperial Coll London Dept Primary Care & Publ Hlth London England Imperial Coll London WHO Collaborating Ctr Publ Hlth Educ & Training London England George Inst Global Hlth TGI UK London England Chinese Ctr Dis Control & Prevent Natl Ctr Chron & Noncommunicable Dis Control & Pr Beijing Peoples R China Harbin Med Univ Sch Publ Hlth Harbin Peoples R China Peking Univ Inst Child & Adolescent Hlth Beijing Peoples R China Univ Melbourne Dept Paediat Parkville Vic Australia Murdoch Childrens Res Inst Ctr Adolescent Hlth Parkville Vic Australia Mashhad Univ Med Sci Fac Med Mashhad Razavi Khorasan Iran Mashhad Univ Med Sci E Learning Ctr Mashhad Razavi Khorasan Iran Mashhad Univ Med Sci Dept Nursing Mashhad Razavi Khorasan Iran Mashhad Univ Med Sci Dept Med Informat Mashhad Razavi Khorasan Iran Mashhad Univ Med Sci Clinial Res Dev Unit Mashhad Razavi Khorasan Iran Shiraz Univ Med Sci Hlth Policy Res Ctr Shiraz Iran Shiraz Univ Med Sci Hlth Informat Management Dept Shiraz Iran Shiraz Univ Med Sci Dept Epidemiol Shiraz Iran Shiraz Univ Med Sci Dept Phys Therapy Shiraz Iran Shahid Beheshti Univ Med Sci Social Determinants Hlth Res Ctr Tehran Iran Shahid Beheshti Univ Med Sci Dept Epidemiol Tehra

Background Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10-24 years during the past three decades. Methods Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10-14, 15-19, and 20-24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings In 2019, 369 061 deaths (of which 214337 [58%] were transport related) and 31.1 million DALYs (of which 16.2 million [52%] were transport related) among adolescents aged 10-24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34.4% (from 17.5 to 11.5 per 100 000) for transport injuries, and by 47.7% (from 15.9 to 8.3 per 100000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80.5% to 42 774 for transport injuries and by 39.4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010-19, the

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