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12,122 results on '"disease"'

2. Publisher Correction: Global estimates on the number of people blind or visually impaired by cataract: a meta-analysis from 2000 to 2020 (Eye, (2024), 10.1038/s41433-024-02961-1)

Author

Global Health, Kayode, Gbenga A., Vision Loss Expert Group of the Global Burden of Disease Study, GBD 2019 Blindness and Vision Impairment Collaborators, Global Health, Kayode, Gbenga A., Vision Loss Expert Group of the Global Burden of Disease Study, and GBD 2019 Blindness and Vision Impairment Collaborators

Published
2024

5. The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data

Author

Michael J. Fox Foundation for Parkinson's Research, Aligning Science Against Parkinson's, National Institutes of Health (US), National Institute on Aging (US), National Institute of Neurological Disorders and Stroke (US), Leonard, Hampton [0000-0003-2390-8110], Illarionova, Anastasia [0000-0002-1711-7155], Moore, Anni [0000-0003-1953-6449], Bustos, Bernabé I. [0000-0003-2679-9503], Huxford, Brook [0000-0002-5908-6983], Storm, Catherine S. [0000-0003-4957-1712], Towns, Clodagh [0000-0001-8418-6241], Yu, Eric [0000-0003-3525-4564], Elsayed, Inas [0000-0003-4646-8218], Lake, Julie [0000-0002-3441-2455], Brolin, Kajsa [0000-0003-4832-922X], Senkevich, Konstantin [0000-0003-3407-5716], Tan, Manuela M. X. [0000-0001-5835-669X], Makarious, Mary B [.0000-0002-7978-1051], Pillay, Nikita Simone [0000-0002-9058-0920], Betancor, Oswaldo Lorenzo [0000-0002-5607-8363], Real, Raquel [0000-0001-8117-742X], Reynolds, Regina H. [0000-0001-6470-7919], Scotton, William J. [0000-0003-0607-3190], Singleton, Andrew [0000-0001-5606-700X], Dey, Sumit [0000-0002-9087-4486], Blauwendraat, Cornelis [0000-0001-9358-8111], Noyce, Alastair [0000-0003-3027-5497], Leonard, Hampton, Murtadha, Ruqaya, Martínez-Carrasco, Alejandro, Jama, Alina, Müller-Nedebock, Amica Corda, Gil-Martínez, Ana Luisa, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabé I., Jadhav, Bharati, Huxford, Brook, Storm, Catherine S., Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P., Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M. X., Periñán, María Teresa, Makarious, Mary B., Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R., Álvarez Jerez, Pilar, Saini, Prabhjyot, Al-Ouran, Rami, Sivakumar, Ramiya, Real, Raquel, Reynolds, Regina H., Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C., Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J., Song, Yeajin, Singleton, Andrew, Nalls, Mike A., Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Noyce, Alastair, International Parkinson’s Disease Genomics Consortium, Global Parkinson’s Genetics Program, Michael J. Fox Foundation for Parkinson's Research, Aligning Science Against Parkinson's, National Institutes of Health (US), National Institute on Aging (US), National Institute of Neurological Disorders and Stroke (US), Leonard, Hampton [0000-0003-2390-8110], Illarionova, Anastasia [0000-0002-1711-7155], Moore, Anni [0000-0003-1953-6449], Bustos, Bernabé I. [0000-0003-2679-9503], Huxford, Brook [0000-0002-5908-6983], Storm, Catherine S. [0000-0003-4957-1712], Towns, Clodagh [0000-0001-8418-6241], Yu, Eric [0000-0003-3525-4564], Elsayed, Inas [0000-0003-4646-8218], Lake, Julie [0000-0002-3441-2455], Brolin, Kajsa [0000-0003-4832-922X], Senkevich, Konstantin [0000-0003-3407-5716], Tan, Manuela M. X. [0000-0001-5835-669X], Makarious, Mary B [.0000-0002-7978-1051], Pillay, Nikita Simone [0000-0002-9058-0920], Betancor, Oswaldo Lorenzo [0000-0002-5607-8363], Real, Raquel [0000-0001-8117-742X], Reynolds, Regina H. [0000-0001-6470-7919], Scotton, William J. [0000-0003-0607-3190], Singleton, Andrew [0000-0001-5606-700X], Dey, Sumit [0000-0002-9087-4486], Blauwendraat, Cornelis [0000-0001-9358-8111], Noyce, Alastair [0000-0003-3027-5497], Leonard, Hampton, Murtadha, Ruqaya, Martínez-Carrasco, Alejandro, Jama, Alina, Müller-Nedebock, Amica Corda, Gil-Martínez, Ana Luisa, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabé I., Jadhav, Bharati, Huxford, Brook, Storm, Catherine S., Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P., Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M. X., Periñán, María Teresa, Makarious, Mary B., Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R., Álvarez Jerez, Pilar, Saini, Prabhjyot, Al-Ouran, Rami, Sivakumar, Ramiya, Real, Raquel, Reynolds, Regina H., Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C., Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J., Song, Yeajin, Singleton, Andrew, Nalls, Mike A., Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Noyce, Alastair, International Parkinson’s Disease Genomics Consortium, and Global Parkinson’s Genetics Program

Abstract

Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.

Published
2023

6. Longitudinal plasma phosphorylated tau 181 tracks disease progression in Alzheimer’s disease

Author

Qiang Dong, Shi-Dong Chen, Xue-Ning Shen, Yu-Yuan Huang, Yu Guo, Jin-Tai Yu, Lan Tan, and Alzheimer’s Disease Neuroimaging Initiative

Subjects
0301 basic medicine, medicine.medical_specialty, tau Proteins, Neurosciences. Biological psychiatry. Neuropsychiatry, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cerebrospinal fluid, Atrophy, Neuroimaging, Alzheimer Disease, Internal medicine, mental disorders, Humans, Medicine, Dementia, Cognitive Dysfunction, Effects of sleep deprivation on cognitive performance, Biological Psychiatry, Amyloid beta-Peptides, medicine.diagnostic_test, business.industry, medicine.disease, Psychiatry and Mental health, 030104 developmental biology, Positron emission tomography, Disease Progression, Cardiology, Biomarker (medicine), business, Biomarkers, 030217 neurology & neurosurgery, Neuroscience, Alzheimer's Disease Neuroimaging Initiative, RC321-571
Abstract

To assess plasma phosphorylated tau181 (p-tau181) as a progression biomarker in Alzheimer’s disease (AD), we examined longitudinal plasma p-tau181 of 1184 participants (403 cognitively normal (CN), 560 patients with mild cognitive impairment (MCI), and 221 with AD dementia) from Alzheimer’s Disease Neuroimaging Initiative (ADNI). The plasma p-tau level was increased at baseline for MCI and AD dementia (mean: CN, 15.4 pg/mL; MCI, 18.4 pg/mL; AD dementia, 23.7 pg/mL; P P P P = 0.002) on positron emission tomography, atrophy in structure imaging (small hippocampal (P = 0.030), middle temporal (P = 0.008), and whole brain (P = 0.027) volume, and large ventricular volume (P = 0.008)), and deteriorated cognitive performance (global cognition and memory, language, executive function, and visuospatial function, all P

Published
2021

7. Mapping routine measles vaccination in low- and middle-income countries

Author

Sbarra, AN, Rolfe, S, Nguyen, JQ, Earl, L, Galles, NC, Marks, A, Abbas, KM, Abbasi-Kangevari, M, Abbastabar, H, Abd-Allah, F, Abdelalim, A, Abdollahi, M, Abegaz, KH, Abiy, HAA, Abolhassani, H, Abreu, LG, Abrigo, MRM, Abushouk, AI, Accrombessi, MMK, Adabi, M, Adebayo, OM, Adekanmbi, V, Adetokunboh, OO, Adham, D, Afarideh, M, Aghaali, M, Ahmad, T, Ahmadi, R, Ahmadi, K, Ahmed, MB, Alanezi, FM, Alanzi, TM, Alcalde-Rabanal, JE, Alemnew, BT, Ali, BA, Ali, M, Alijanzadeh, M, Alinia, C, Alipoor, R, Alipour, V, Alizade, H, Aljunid, SM, Almasi, A, Almasi-Hashiani, A, Al-Mekhlafi, HM, Altirkawi, KA, Amare, B, Amini, S, Amini-Rarani, M, Amiri, F, Amit, AML, Amugsi, DA, Ancuceanu, R, Andrei, CL, Anjomshoa, M, Ansari, F, Ansari-Moghaddam, A, Ansha, MG, Antonio, CAT, Antriyandarti, E, Anvari, D, Arabloo, J, Arab-Zozani, M, Aremu, O, Armoon, B, Aryal, KK, Arzani, A, Asadi-Aliabadi, M, Asgari, S, Atafar, Z, Ausloos, M, Awoke, N, Quintanilla, BPA, Ayanore, MA, Aynalem, YA, Azadmehr, A, Azari, S, Babaee, E, Badawi, A, Badiye, AD, Bahrami, MA, Baig, AA, Bakhtiari, A, Balakrishnan, S, Banach, M, Banik, PC, Barac, A, Baradaran-Seyed, Z, Baraki, AG, Basu, S, Bayati, M, Bayou, YT, Bedi, N, Behzadifar, M, Bell, ML, Berbada, DA, Berhe, K, Bhattarai, S, Bhutta, ZA, Bijani, A, Birhanu, M, Bisanzio, D, Biswas, A, Bohlouli, S, Bolla, SR, Borzouei, S, Brady, OJ, Bragazzi, NL, Briko, AN, Briko, NI, Nagaraja, SB, Butt, ZA, Cámera, LA, Campos-Nonato, IR, Car, J, Cárdenas, R, Carvalho, F, Castaldelli-Maia, JM, Castro, F, Chattu, VK, Chehrazi, M, Chin, KL, Chu, D-T, Cook, AJ, Cormier, NM, Cunningham, B, Dahlawi, SMA, Damiani, G, Dandona, R, Dandona, L, Danovaro, MC, Dansereau, E, Daoud, F, Darwesh, AM, Darwish, AH, Das, JK, Weaver, ND, De Neve, J-W, Demeke, FM, Demis, AB, Denova-Gutiérrez, E, Desalew, A, Deshpande, A, Desta, DM, Dharmaratne, SD, Dhungana, GP, Dianatinasab, M, Diaz, D, Dipeolu, IO, Djalalinia, S, Do, HT, Dorostkar, F, Doshmangir, L, Doyle, KE, Dunachie, SJ, Duraes, AR, Kalan, ME, Leylabadlo, HE, Edinur, HA, Effiong, A, Eftekhari, A, El, Sayed, I, El, Sayed, Zaki, M, Elema, TB, Elhabashy, HR, El-Jaafary, SI, Elsharkawy, A, Emamian, MH, Enany, S, Eshrati, B, Eskandari, K, Eskandarieh, S, Esmaeilnejad, S, Esmaeilzadeh, F, Esteghamati, A, Etisso, AE, Farahmand, M, Faraon, EJA, Fareed, M, Faridnia, R, Farioli, A, Farzadfar, F, Fattahi, N, Fazlzadeh, M, Fereshtehnejad, S-M, Fernandes, E, Filip, I, Fischer, F, Foigt, NA, Folayan, MO, Foroutan, M, Fukumoto, T, Fullman, N, Gad, MM, Geberemariyam, BS, Gebrehiwot, TT, Gebrehiwot, AM, Gebremariam, KT, Gebremedhin, KB, Gebremeskel, GG, Gebreslassie, AA, Gedefaw, GA, Gezae, KE, Ghadiri, K, Ghaffari, R, Ghaffarifar, F, Ghajarzadeh, M, Gheshlagh, RG, Ghashghaee, A, Ghiasvand, H, Gholamian, A, Gilani, SA, Gill, PS, Girmay, A, Gomes, NGM, Gopalani, SV, Goulart, BNG, Grada, A, Guimarães, RA, Guo, Y, Gupta, R, Hafezi-Nejad, N, Haj-Mirzaian, A, Handiso, DW, Hanif, A, Haririan, H, Hasaballah, AI, Hasan, MM, Hasanpoor, E, Hasanzadeh, A, Hassanipour, S, Hassankhani, H, Heidari-Soureshjani, R, Henry, NJ, Herteliu, C, Heydarpour, F, Hollerich, GI, Rad, EH, Hoogar, P, Hossain, N, Hosseini, M, Hosseinzadeh, M, Househ, M, Hu, G, Huda, TM, Humayun, A, Ibitoye, SE, Ikilezi, G, Ilesanmi, OS, Ilic, IM, Ilic, MD, Imani-Nasab, MH, Inbaraj, LR, Iqbal, U, Irvani, SSN, Islam, SMS, Islam, MM, Iwu, CJ, Iwu, CCD, Jadidi-Niaragh, F, Jafarinia, M, Jahanmehr, N, Jakovljevic, M, Jalali, A, Jalilian, F, Javidnia, J, Jenabi, E, Jha, V, Ji, JS, John, O, Johnson, KB, Joukar, F, Jozwiak, JJ, Kabir, Z, Kabir, A, Kalani, H, Kalankesh, LR, Kalhor, R, Kamal, Z, Kanchan, T, Kapoor, N, Karami, M, Matin, BK, Karch, A, Karimi, SE, Kayode, GA, Karyani, AK, Keiyoro, PN, Khader, YS, Khafaie, MA, Khammarnia, M, Khan, MS, Khan, EA, Khan, J, Khan, MN, Khatab, K, Khater, MM, Khatib, MN, Khayamzadeh, M, Khazaei, M, Khazaei, S, Khosravi, A, Khubchandani, J, Kianipour, N, Kim, YJ, Kimokoti, RW, Kinyoki, DK, Kisa, A, Kisa, S, Kolola, T, Komaki, H, Kosen, S, Koul, PA, Koyanagi, A, Kraemer, MUG, Krishan, K, Kuate Defo, B, Kumar, M, Kumar, P, Kumar, GA, Kusuma, D, La Vecchia, C, Lacey, B, Lad, SD, Lal, DK, Lam, F, Lami, FH, Lansingh, VC, Larson, HJ, Lasrado, S, Lee, SWH, Lee, PH, LeGrand, KE, Lenjebo, TL, Li, S, Liang, X, Liu, PY, Lopukhov, PD, Machado, DB, Mahasha, PW, Mahdavi, MM, Maheri, M, Mahotra, NB, Maled, V, Maleki, S, Malik, MA, Malta, DC, Mansour-Ghanaei, F, Mansouri, B, Mansourian, M, Mansournia, MA, Martins-Melo, FR, Masaka, A, Mayala, BK, Mehndiratta, MM, Mehri, F, Mehta, KM, Memiah, PTN, Mendoza, W, Menezes, RG, Mengesha, MB, Mengesha, EW, Mestrovic, T, Mihretie, KM, Miller-Petrie, MK, Mills, EJ, Milne, GJ, Mirabi, P, Mirrakhimov, EM, Mirzaei, R, Mirzaei, M, Mirzaei, HR, Mirzaei, H, Mirzaei-Alavijeh, M, Moazen, B, Moghadaszadeh, M, Mohamadi, E, Mohammad, DK, Mohammad, Y, Mohammad, KA, Mohammad Gholi Mezerji, N, Mohammadbeigi, A, Mohammadian-Hafshejani, A, Mohammadpourhodki, R, Mohammed, S, Mohammed, AS, Mohammed, H, Mohebi, F, Mokdad, AH, Monasta, L, Moosavi, MA, Moosazadeh, M, Moradi, G, Moradi, M, Moradi-Joo, M, Moradi-Lakeh, M, Moradzadeh, R, Moraga, P, Mosapour, A, Mouodi, S, Mousavi, SM, Khaneghah, AM, Mueller, UO, Muluneh, AG, Munro, SB, Murray, CJL, Murthy, GVS, Muthupandian, S, Naderi, M, Nagarajan, AJ, Naghavi, M, Nangia, V, Nansseu, JR, Nayak, VC, Nazari, J, Ndwandwe, DE, Negoi, I, Ngunjiri, JW, Nguyen, HLT, Nguyen, CTK, Nguyen, TH, Nigatu, YT, Nikbakhsh, R, Nikfar, S, Nikpoor, AR, Ningrum, DNA, Nnaji, CA, Oh, I-H, Oladnabi, M, Olagunju, AT, Olusanya, JO, Olusanya, BO, Bali, AO, Omer, MO, Onwujekwe, OE, Osgood-Zimmerman, AE, Owolabi, MO, P, A, M, Padubidri, JR, Pakshir, K, Pana, A, Pandey, A, Pando-Robles, V, Pashaei, T, Pasupula, DK, Paternina-Caicedo, AJ, Patton, GC, Pazoki Toroudi, H, Pepito, VCF, Pescarini, JM, Pigott, DM, Pilgrim, T, Pirsaheb, M, Poljak, M, Postma, MJ, Pourjafar, H, Pourmalek, F, Pourmirza, Kalhori, R, Prada, SI, Prakash, S, Quazi Syed, Z, Quintana, H, Rabiee, N, Rabiee, M, Radfar, A, Rafiei, A, Rahim, F, Rajati, F, Rameto, MA, Ramezanzadeh, K, Ranabhat, CL, Rao, SJ, Rasella, D, Rastogi, P, Rathi, P, Rawaf, S, Rawaf, DL, Rawal, L, Rawassizadeh, R, Rawat, R, Renjith, V, Renzaho, AMN, Reshmi, B, Reta, MA, Rezaei, N, Rezai, MS, Rezapour, A, Riahi, SM, Ribeiro, AI, Rickard, J, Rios-Blancas, M, Rios-González, CM, Roever, L, Rostamian, M, Rubino, S, Rwegerera, GM, Saad, AM, Saadatagah, S, Sabour, S, Sadeghi, E, Moghaddam, SS, Saeidi, S, Sagar, R, Sahebkar, A, Sahraian, MA, Sajadi, SM, Salahshoor, MR, Salam, N, Salem, H, Salem, MR, Salomon, JA, Kafil, HS, Sambala, EZ, Samy, AM, Saraswathy, SYI, Sarmiento-Suárez, R, Saroshe, S, Sartorius, B, Sarveazad, A, Sathian, B, Sathish, T, Schaeffer, LE, Schwebel, DC, Senthilkumaran, S, Shabaninejad, H, Shahabi, S, Shaheen, AA, Shaikh, MA, Shalash, AS, Shams-Beyranvand, M, Shamsi, MB, Shamsizadeh, M, Sharafi, K, Sharifi, H, Sheikh, A, Sheikhtaheri, A, Shetty, RS, Shiferaw, WS, Shigematsu, M, Shin, JI, Shirkoohi, R, Siabani, S, Siddiqi, TJ, Silverberg, JIS, Simonetti, B, Singh, JA, Sinha, DN, Sinke, AH, Soheili, A, Sokhan, A, Soltani, S, Soofi, M, Sorrie, MB, Soyiri, IN, Spotin, A, Spurlock, EE, Sreeramareddy, CT, Sudaryanto, A, Sufiyan, MB, Suleria, HAR, Abdulkader, RS, Taherkhani, A, Tapak, L, Taveira, N, Taymoori, P, Tefera, YM, Tehrani-Banihashemi, A, Teklehaimanot, BF, Tekulu, GH, Tesfay, BE, Tessema, ZT, Tessema, B, Thankappan, KR, Tohidinik, HR, Topor-Madry, R, Tovani-Palone, MR, Tran, BX, Uddin, R, Ullah, I, Umeokonkwo, CD, Unnikrishnan, B, Upadhyay, E, Usman, MS, Vaezi, M, Valadan, Tahbaz, S, Valdez, PR, Vasseghian, Y, Veisani, Y, Violante, FS, Vollmer, S, Waheed, Y, Wakefield, J, Wang, Y, Wang, Y-P, Weldesamuel, GT, Werdecker, A, Westerman, R, Wiangkham, T, Wiens, KE, Wiysonge, CS, Woldu, G, Wondafrash, DZ, Wonde, TE, Wu, A-M, Yadollahpour, A, Jabbari, SHY, Yamada, T, Yaya, S, Yazdi-Feyzabadi, V, Yeheyis, TY, Yeshaw, Y, Yilgwan, CS, Yip, P, Yonemoto, N, Younis, MZ, Yousefi, Z, Yousefifard, M, Yousefinezhadi, T, Yu, C, Yusefzadeh, H, Zadey, S, Zahirian, Moghadam, T, Zaki, L, Zaman, SB, Zamani, M, Zamanian, M, Zandian, H, Zangeneh, A, Zarei, F, Zerfu, TA, Zhang, Y, Zhang, Z-J, Zhao, X-JG, Zhou, M, Ziapour, A, Hay, SI, Lim, SS, Mosser, JF, Local Burden of Disease Vaccine Coverage Collaborators, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Microbes in Health and Disease (MHD), HUS Comprehensive Cancer Center, Clinicum, Department of Oncology, Sbarra, Alyssa N., Rolfe, Sam, Nguyen, Jason Q., Earl, Lucas, Ahmed, MB, Mosser, Jonathan F, Collaborators, Local Burden of Disease Vaccine Coverage, Bill & Melinda Gates Foundation, Alexander von Humboldt-Stiftung, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Universiti Sains Malaysia (Malasia), Panjab University (India), NIHR - Oxford Biomedical Research Centre (Reino Unido), Australian Research Council, Instituto de Saúde Pública da Universidade do Porto, Local Burden Dis Educ Attainment C, Local Burden of Disease Vaccine Coverage Collaborator, and Violante FS

Subjects
and promotion of well-being, Vacunación Masiva, Internationality, Disease prevention, children under 5 years old, Geographic Mapping, Rural Health, medicine.disease_cause, Cross-reactivity, 0302 clinical medicine, RA0421, Vaccination Refusal, 030212 general & internal medicine, Child, immunity patterns, Pediatric, 0303 health sciences, Public health, Multidisciplinary, biology, Vaccination, Uncertainty, IMMUNIZATION, 3142 Public health care science, environmental and occupational health, COVERAGE, 3. Good health, TIME, 3.4 Vaccines, Child, Preschool, Infectious diseases, A990 Medicine and Dentistry not elsewhere classified, Antibody, Engineering sciences. Technology, AFRICA, General Science & Technology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, 610 Medicine & health, Global Vaccine Action Plan (GVAP), Local Burden of Disease Vaccine Coverage Collaborators, Article, Vaccine Related, 03 medical and health sciences, measles vaccine, Measels, Low- and middle-income countries, Local burden of disease, Clinical Research, medicine, Humans, Healthcare Disparities, Preschool, PROGRESS, 030304 developmental biology, business.industry, MORTALITY, Developed Countries, Prevention, Comment, Vacunación, Urban Health, Prevention of disease and conditions, Virology, Coronavirus, Good Health and Well Being, Cobertura de Vacunación, biology.protein, Immunization, business, Measles
Abstract

The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2 pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children., Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

Published
2021
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8. Exome-wide age-of-onset analysis reveals exonic variants in ERN1 and SPPL2C associated with Alzheimer’s disease

Author

Alzheimer’s Disease Neuroimaging Initiative, Manolis Kellis, David A. Bennett, Alexander M. Kulminski, Liang He, Yury Loika, and Yongjin Park

Subjects
0301 basic medicine, Apolipoprotein E4, Genome-wide association study, Protein Serine-Threonine Kinases, Biology, Predictive markers, Polymorphism, Single Nucleotide, Article, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, Endoribonucleases, Exome Sequencing, Aspartic Acid Endopeptidases, Humans, Missense mutation, Exome, Genetic Predisposition to Disease, Clinical genetics, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Genetic association, Genetics, Membrane Proteins, Minor allele frequency, Psychiatry and Mental health, 030104 developmental biology, Posterior cingulate, Expression quantitative trait loci, 030217 neurology & neurosurgery, Genome-Wide Association Study, Alzheimer's Disease Neuroimaging Initiative
Abstract

Despite recent discoveries in genome-wide association studies (GWAS) of genomic variants associated with Alzheimer’s disease (AD), its underlying biological mechanisms are still elusive. The discovery of novel AD-associated genetic variants, particularly in coding regions and from APOEε4 non-carriers, is critical for understanding the pathology of AD. In this study, we carried out an exome-wide association analysis of age-of-onset of AD with ~20,000 subjects and placed more emphasis on APOEε4 non-carriers. Using Cox mixed-effects models, we find that age-of-onset shows a stronger genetic signal than AD case-control status, capturing many known variants with stronger significance, and also revealing new variants. We identified two novel variants, rs56201815, a rare synonymous variant in ERN1, and rs12373123, a common missense variant in SPPL2C in the MAPT region in APOEε4 non-carriers. Besides, a rare missense variant rs144292455 in TACR3 showed the consistent direction of effect sizes across all studies with a suggestive significant level. In an attempt to unravel their regulatory and biological functions, we found that the minor allele of rs56201815 was associated with lower average FDG uptake across five brain regions in ADNI. Our eQTL analyses based on 6198 gene expression samples from ROSMAP and GTEx revealed that the minor allele of rs56201815 was potentially associated with elevated expression of ERN1, a key gene triggering unfolded protein response (UPR), in multiple brain regions, including the posterior cingulate cortex and nucleus accumbens. Our cell-type-specific eQTL analysis using ~80,000 single nuclei in the prefrontal cortex revealed that the protective minor allele of rs12373123 significantly increased the expression of GRN in microglia, and was associated with MAPT expression in astrocytes. These findings provide novel evidence supporting the hypothesis of the potential involvement of the UPR to ER stress in the pathological pathway of AD, and also give more insights into underlying regulatory mechanisms behind the pleiotropic effects of rs12373123 in multiple degenerative diseases including AD and Parkinson’s disease.

Published
2021

9. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Neurogenetica, Cardiovasculaire Epi Team 7a, Brain, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Epidemiology & Health Economics, Cardiovasculaire Epi Team 3, Advanced Nursing, Onderzoek Precision medicine, Neurologen, PRECISE4Q Consortium, FinnGen Consortium, NINDS Stroke Genetics Network (SiGN), MEGASTROKE Consortium, SIREN Consortium, China Kadoorie Biobank Collaborative Group, VA Million Veteran Program, International Stroke Genetics Consortium (ISGC), Biobank Japan, CHARGE Consortium, GIGASTROKE Consortium, COMPASS Consortium, INVENT Consortium, Dutch Parelsnoer Initiative (PSI) Cerebrovascular Disease Study Group, Estonian Biobank, Neurogenetica, Cardiovasculaire Epi Team 7a, Brain, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Epidemiology & Health Economics, Cardiovasculaire Epi Team 3, Advanced Nursing, Onderzoek Precision medicine, Neurologen, PRECISE4Q Consortium, FinnGen Consortium, NINDS Stroke Genetics Network (SiGN), MEGASTROKE Consortium, SIREN Consortium, China Kadoorie Biobank Collaborative Group, VA Million Veteran Program, International Stroke Genetics Consortium (ISGC), Biobank Japan, CHARGE Consortium, GIGASTROKE Consortium, COMPASS Consortium, INVENT Consortium, Dutch Parelsnoer Initiative (PSI) Cerebrovascular Disease Study Group, and Estonian Biobank

Published
2022

10. A rare mutation in UNC5C predisposes to late-onset Alzheimer's disease and increases neuronal cell death

Author

Wetzel-Smith, Monica K., Hunkapiller, Julie, Bhangale, Tushar R., Srinivasan, Karpagam, Maloney, Janice A., Atwal, Jasvinder K., Sa, Susan M., Yaylaoglu, Murat B., Foreman, Oded, Ortmann, Ward, Rathore, Nisha, Hansen, David V., Tessier- Lavigne, Marc, Consortium, Alzheimers Disease Genetics, Mayeux, Richard, Pericak-Vance, Margaret, Haines, Jonathan, Farrer, Lindsay A., Schellenberg, Gerard D., Goate, Alison, Behrens, Timothy W., Cruchaga, Carlos, Watts, Ryan J., and Graham, Robert R.

Subjects
United States. National Institute on Aging, Analysis, Genetic aspects, Risk factors, Gene mutation -- Analysis, Cell death -- Analysis, Glutamate -- Analysis, Alzheimer's disease -- Genetic aspects -- Risk factors
Abstract

Although progress has been made in defining the genetic basis of Alzheimer's disease (AD), much of the heritability of AD remains to be discovered (1-12). We elected to study a [...], We have identified a rare coding mutation, T835M (rs137875858), in the UNC5C netrin receptor gene that segregated with disease in an autosomal dominant pattern in two families enriched for late-onset Alzheimer's disease and that was associated with disease across four large case-control cohorts (odds ratio = 2.15, [P.sub.meta] = 0.0095). T835M alters a conserved residue in the hinge region of UNC5C, and in vitro studies demonstrate that this mutation leads to increased cell death in human HEK293T cells and in rodent neurons. Furthermore, neurons expressing T835M UNC5C are more susceptible to cell death from multiple neurotoxic stimuli, including β-amyloid (Aβ), glutamate and staurosporine. On the basis of these data and the enriched hippocampal expression of UNC5C in the adult nervous system, we propose that one possible mechanism in which T835M UNC5C contributes to the risk of Alzheimer's disease is by increasing susceptibility to neuronal cell death, particularly in vulnerable regions of the Alzheimer's disease brain.

Published
2014

11. Single-cell multi-omics analysis of the immune response in COVID-19

Author

Stephenson, Emily, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID-19 BioResource Collaboration, Kingston, Nathalie, Owehand, Willem H., Gräf, Stefan, Allison, John, Ovington, Nigel, Stirrups, Kathleen E., Townsend, Paul, and Walker, Neil

Abstract

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy., Nature Medicine, 27 (5), ISSN:1078-8956, ISSN:1546-170X

Published
2021

13. Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome

Author

Remuzgo Martínez, Sara, Atienza Mateo, Belén, Ocejo Vinyals, J. Gonzalo, Genre, Fernanda, Pulito Cueto, Verónica, Mora Cuesta, Víctor M., Iturbe Fernández, David, Lera Gómez, Leticia, Pérez Fernández, Raquel, Prieto Peña, Diana, Irure, Juan, Romero Bueno, Fredeswinda, Sanchez Pernaute, Olga, Alonso Moralejo, Rodrigo, Nuño, Laura, Bonilla, Gema, Vicente Rabaneda, Esther F., Grafia, Ignacio, Prieto González, Sergio, Narváez, Javier, Trallero Araguas, Ernesto, Selva O’Callaghan, Albert, Ortego Centeno, Norberto, Pérez Gómez, Nair, Mera, Antonio, Martínez Barrio, Julia, Moriano, Clara, Díez, Elvira, Calvo Alén, Jaime, Balsa, Alejandro, Ussetti, María Piedad, Laporta, Rosalía, Berastegui, Cristina, Solé, Amparo, Gualillo, Oreste, Cavagna, Lorenzo, Cifrián, José M., Renzoni, Elisabetta A., Castañeda, Santos, López Mejías, Raquel, González Gay, Miguel A., Spanish Biomarkers Of Antisynthetase Syndrome Consortium, Spanish Biomarkers Of Interstitial Lung Disease Consortium, Universidad de Cantabria, Institut Català de la Salut, [Remuzgo-Martínez S, Genre F, Pulito-Cueto V] Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Diseases of the Musculoskeletal System, IDIVAL, 39011 Santander, Spain. [Atienza-Mateo B] Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Diseases of the Musculoskeletal System, IDIVAL, 39011 Santander, Spain. López Albo’ Post Residency Programme, Hospital Universitario Marqués de Valdecilla, Santander, Spain. Rheumatology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain. [Ocejo-Vinyals JG] Department of Immunology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. [Mora-Cuesta VM] Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Diseases of the Musculoskeletal System, IDIVAL, 39011 Santander, Spain. Pneumology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain. [Trallero-Araguas E] Unitat de Reumatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Selva-O'Callaghan A] Unitat de Malalties Autoimmunes Sistèmiques, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Interstitial [DISEASES], Antisynthetase syndrome, Gastroenterology, Idiopathic pulmonary fibrosis, Genètica mèdica, 0302 clinical medicine, fenómenos genéticos::variación genética::polimorfismo genético::polimorfismo de nucleótido único [FENÓMENOS Y PROCESOS], Gene Frequency, Polymorphism (computer science), Genotype, Malalties autoimmunitàries - Aspectes genètics, diagnóstico::diagnóstico diferencial [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], 0303 health sciences, Multidisciplinary, Medical genetics, Fibrosi pulmonar, Middle Aged, respiratory system, 3. Good health, Up-Regulation, medicine.anatomical_structure, Phenotype, Biomarker (medicine), Medicine, Female, Adult, medicine.medical_specialty, Pulmons - Malalties - Aspectes genètics, Science, Polymorphism, Single Nucleotide, Article, Pulmonary fibrosis, Diagnosis, Differential, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Allele, Allele frequency, Genetic Association Studies, 030304 developmental biology, 030203 arthritis & rheumatology, Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [PHENOMENA AND PROCESSES], Lung, Myositis, business.industry, Polimorfisme genètic, Mucin-1, medicine.disease, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, Cross-Sectional Studies, enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares intersticiales [ENFERMEDADES], Spain, Case-Control Studies, Diagnosis::Diagnosis, Differential [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], business, Lung Diseases, Interstitial, Idiopathic inflammatory myopathies, Biomarkers
Abstract

Study partially supported by a grant from Spanish Society of Pulmonology and Thoracic Surgery (SEPAR 474-2017) and from Euronanomed III / Instituto de Salud Carlos III (ISCIII) (AC17/00027) awarded to SC. SR-M is supported by funds of the RETICS Program (RD16/0012/0009) from the ISCIII, co-funded by the European Regional Development Fund. BA-M is recipient of a ‘López Albo’ Post-Residency Programme funded by Servicio Cántabro de Salud. VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). LL-G is supported by funds from IDIVAL (INNVAL 20/06). RP-F is supported by funds of START project (FOREUM18/34). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, ‘Investing in your future’) (CM20/00006). OG is staff personnel of Xunta de Galicia (Servizo Galego de Saude (SERGAS)) through a research-staff stabilization contract (ISCIII/SERGAS) and his work is funded by ISCIII and the European Union FEDER fund (RD16/0012/0014 (RIER) and PI17/00409). He is beneficiary of project funds from the Research Executive Agency (REA) of the European Union in the framework of MSCA-RISE Action of the H2020 Programme, Project 734899—Olive-Net. RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the ESF (CP16/00033)., Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients., European Union FEDER fund PI17/00409, Servicio Cántabro de Salud, Servizo Galego de Saude, Spanish Society of Pulmonology and Thoracic Surgery SEPAR 474-2017, European Commission EC 734899, CP16/00033, Research Executive Agency, Instituto de Salud Carlos III AC17/00027, CM20/00006, RD16/0012/0009, RD16/0012/0014, European Social Fund, European Regional Development Fund, Foundation for Research in Rheumatology, Instituto de Investigación Marqués de Valdecilla INNVAL 20/06, PREVAL 18/01, Servicio Gallego de Salud, START, Global Change System for Analysis, Research, and Training FOREUM18/34

Published
2021

14. Identification of limb-specific Lmx1b auto-regulatory modules with Nail-patella syndrome pathogenicity

Author

Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Rare Disorders Consortium Disease Network (US), Haro, Endika, Petit, Florence, Pira, Charmaine, Spady, Conor, Lucas, Sara, Yorozuya, Lauren I., Gray, Austin L., Escande, Fabienne, Jourdain, Anne-Sophie, Nguyen, Andy, Fellmann, Florence, Good, Jean-Marc, Francannet, Christine, Manouvrier-Hanu, Sylvie, Ros, María A., Oberg, Kerby C., Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Rare Disorders Consortium Disease Network (US), Haro, Endika, Petit, Florence, Pira, Charmaine, Spady, Conor, Lucas, Sara, Yorozuya, Lauren I., Gray, Austin L., Escande, Fabienne, Jourdain, Anne-Sophie, Nguyen, Andy, Fellmann, Florence, Good, Jean-Marc, Francannet, Christine, Manouvrier-Hanu, Sylvie, Ros, María A., and Oberg, Kerby C.

Abstract

LMX1B haploinsufficiency causes Nail-patella syndrome (NPS; MIM 161200), characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma. Accordingly in mice, Lmx1b has been shown to play crucial roles in the development of the limb, kidney and eye. Although one functional allele of Lmx1b appears adequate for development, Lmx1b null mice display ventral-ventral distal limbs with abnormal kidney, eye and cerebellar development, more disruptive, but fully concordant with NPS. In Lmx1b functional knockouts (KOs), Lmx1b transcription in the limb is decreased nearly 6-fold, indicating autoregulation. Herein, we report on two conserved Lmx1b-associated cis-regulatory modules (LARM1 and LARM2) that are bound by Lmx1b, amplify Lmx1b expression with unique spatial modularity in the limb, and are necessary for Lmx1b-mediated limb dorsalization. These enhancers, being conserved across vertebrates (including coelacanth, but not other fish species), and required for normal locomotion, provide a unique opportunity to study the role of dorsalization in the fin to limb transition. We also report on two NPS patient families with normal LMX1B coding sequence, but with loss-of-function variations in the LARM1/2 region, stressing the role of regulatory modules in disease pathogenesis.

Published
2021

15. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W., Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C., Naj, Adam C., Boland, Anne, Vronskaya, Maria, van der Lee, Sven J, Amlie-Wolf, Alex, Bellenguez, Celine, Frizatti, Aura, Chouraki, Vincent, Schmidt, Helena, Hakonarson, Hakon, Munger, Ron, Schmidt, Reinhold, Farrer, Lindsay A., Van Broeckhoven, Christine, O'Donovan, Michael C., Destefano, Anita L., Jones, Lesley, Haines, Jonathan L., Deleuze, Jean-Francois, Owen, Michael J., Gudnason, Vilmundur, Mayeux, Richard P., Escott-Price, Valentina, Psaty, Bruce M., Ruiz, Agustin, Ramirez, Alfredo, Wang, Li-San, van Duijn, Cornelia M., Holmans, Peter A., Seshadri, Sudha, Williams, Julie, Amouyel, Philippe, Schellenberg, Gerard D., Lambert, Jean-Charles, Pericak-Vance, Margaret A., Alzheimer's Disease Genetics Consortium (ADGC), European Alzheimer's Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in Alzheimer's Disease Consortium (GERAD/PERADES), and Morgan, Kevin

Abstract

Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer’s or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer’s disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P= 1.32 × 10−7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

Published
2019

16. Nat Genet

Author

KUNKLE, B. W., GRENIER-BOLEY, B., SIMS, R., BIS, J. C., DAMOTTE, V., NAJ, A. C., BOLAND, A., VRONSKAYA, M., VAN DER LEE, S. J., AMLIE-WOLF, A., BELLENGUEZ, C., FRIZATTI, A., CHOURAKI, V., MARTIN, E. R., SLEEGERS, K., BADARINARAYAN, N., JAKOBSDOTTIR, J., HAMILTON-NELSON, K. L., MORENO-GRAU, S., OLASO, R., RAYBOULD, R., CHEN, Y., KUZMA, A. B., HILTUNEN, M., MORGAN, T., AHMAD, S., VARDARAJAN, B. N., EPELBAUM, J., HOFFMANN, P., BOADA, M., BEECHAM, G. W., GARNIER, J. G., HAROLD, D., FITZPATRICK, A. L., VALLADARES, O., MOUTET, M. L., GERRISH, A., QU, L., BACQ, D., DENNING, N., JIAN, X., ZHAO, Y., DEL ZOMPO, M., FOX, N. C., CHOI, S. H., MATEO, I., HUGHES, J. T., ADAMS, H. H., MALAMON, J., SANCHEZ-GARCIA, F., PATEL, Y., BRODY, J. A., DOMBROSKI, B. A., NARANJO, M. C. D., DANIILIDOU, M., EIRIKSDOTTIR, G., MUKHERJEE, S., WALLON, D., UPHILL, J., ASPELUND, T., CANTWELL, L. B., GARZIA, F., GALIMBERTI, D., HOFER, E., BUTKIEWICZ, M., FIN, B., SCARPINI, E., SARNOWSKI, C., BUSH, W. S., MESLAGE, S., KORNHUBER, J., WHITE, C. C., SONG, Y., BARBER, R. C., ENGELBORGHS, S., SORDON, S., VOIJNOVIC, D., ADAMS, P. M., VANDENBERGHE, R., MAYHAUS, M., CUPPLES, L. A., ALBERT, M. S., DE DEYN, P. P., GU, W., HIMALI, J. J., BEEKLY, D., SQUASSINA, A., HARTMANN, A. M., ORELLANA, A., BLACKER, D., RODRIGUEZ-RODRIGUEZ, E., LOVESTONE, S., GARCIA, M. E., DOODY, R. S., MUNOZ-FERNADEZ, C., SUSSAMS, R., LIN, H., FAIRCHILD, T. J., BENITO, Y. A., HOLMES, C., KARAMUJIC-COMIC, H., FROSCH, M. P., THONBERG, H., MAIER, W., ROSCHUPKIN, G., GHETTI, B., GIEDRAITIS, V., KAWALIA, A., LI, S., HUEBINGER, R. M., KILANDER, L., MOEBUS, S., HERNANDEZ, I., KAMBOH, M. I., BRUNDIN, R., TURTON, J., YANG, Q., KATZ, M. J., CONCARI, L., LORD, J., BEISER, A. S., KEENE, C. D., HELISALMI, S., KLOSZEWSKA, I., KUKULL, W. A., KOIVISTO, A. M., LYNCH, A., TARRAGA, L., LARSON, E. B., HAAPASALO, A., LAWLOR, B., MOSLEY, T. H., LIPTON, R. B., SOLFRIZZI, V., GILL, M., LONGSTRETH, W. T. Jr., MONTINE, T. J., FRISARDI, V., DIEZ-FAIREN, M., RIVADENEIRA, F., PETERSEN, R. C., DERAMECOURT, V., ALVAREZ, I., SALANI, F., CIARAMELLA, A., BOERWINKLE, E., REIMAN, E. M., FIEVET, N., ROTTER, J. I., REISCH, J. S., HANON, O., CUPIDI, C., ANDRE UITTERLINDEN, A. G., ROYALL, D. R., DUFOUIL, Carole, MALETTA, R. G., DE ROJAS, I., SANO, M., BRICE, A., CECCHETTI, R., GEORGE-HYSLOP, P. S., RITCHIE, K., TSOLAKI, M., TSUANG, D. W., DUBOIS, B., CRAIG, D., WU, C. K., SOININEN, H., AVRAMIDOU, D., ALBIN, R. L., FRATIGLIONI, L., GERMANOU, A., APOSTOLOVA, L. G., KELLER, L., KOUTROUMANI, M., ARNOLD, S. E., PANZA, F., GKATZIMA, O., ASTHANA, S., HANNEQUIN, D., WHITEHEAD, P., ATWOOD, C. S., CAFFARRA, P., HAMPEL, H., QUINTELA, I., CARRACEDO, A., LANNFELT, L., RUBINSZTEIN, D. C., BARNES, L. L., PASQUIER, F., FROLICH, L., BARRAL, S., MCGUINNESS, B., BEACH, T. G., JOHNSTON, J. A., BECKER, J. T., PASSMORE, P., BIGIO, E. H., SCHOTT, J. M., BIRD, T. D., WARREN, J. D., BOEVE, B. F., LUPTON, M. K., BOWEN, J. D., PROITSI, P., BOXER, A., POWELL, J. F., BURKE, J. R., KAUWE, J. S. K., BURNS, J. M., MANCUSO, M., BUXBAUM, J. D., BONUCCELLI, U., CAIRNS, N. J., MCQUILLIN, A., CAO, C., LIVINGSTON, G., CARLSON, C. S., BASS, N. J., CARLSSON, C. M., HARDY, J., CARNEY, R. M., BRAS, J., CARRASQUILLO, M. M., GUERREIRO, R., ALLEN, M., CHUI, H. C., FISHER, E., MASULLO, C., CROCCO, E. A., DECARLI, C., BISCEGLIO, G., DICK, M., MA, L., DUARA, R., GRAFF-RADFORD, N. R., EVANS, D. A., HODGES, A., FABER, K. M., SCHERER, M., FALLON, K. B., RIEMENSCHNEIDER, M., FARDO, D. W., HEUN, R., FARLOW, M. R., KOLSCH, H., FERRIS, S., LEBER, M., FOROUD, T. M., HEUSER, I., GALASKO, D. R., GIEGLING, I., GEARING, M., HULL, M., GESCHWIND, D. H., GILBERT, J. R., GREEN, R. C., MAYO, K., GROWDON, J. H., FEULNER, T., HAMILTON, R. L., HARRELL, L. E., DRICHEL, D., HONIG, L. S., CUSHION, T. D., HUENTELMAN, M. J., HOLLINGWORTH, P., HULETTE, C. M., HYMAN, B. T., MARSHALL, R., JARVIK, G. P., MEGGY, A., ABNER, E., MENZIES, G. E., JIN, L. W., LEONENKO, G., REAL, L. M., JUN, G. R., BALDWIN, C. T., GROZEVA, D., KARYDAS, A., RUSSO, G., KAYE, J. A., KIM, R., JESSEN, F., KOWALL, N. W., VELLAS, B., KRAMER, J. H., VARDY, E., LAFERLA, F. M., JOCKEL, K. H., LAH, J. J., DICHGANS, M., LEVERENZ, J. B., MANN, D., LEVEY, A. I., PICKERING-BROWN, S., LIEBERMAN, A. P., KLOPP, N., LUNETTA, K. L., WICHMANN, H. E., LYKETSOS, C. G., MORGAN, K., MARSON, D. C., BROWN, K., MARTINIUK, F., MEDWAY, C., MASH, D. C., NOTHEN, M. M., MASLIAH, E., HOOPER, N. M., MCCORMICK, W. C., DANIELE, A., MCCURRY, S. M., BAYER, A., MCDAVID, A. N., GALLACHER, J., MCKEE, A. C., VAN DEN BUSSCHE, H., MESULAM, M., BRAYNE, C., MILLER, B. L., RIEDEL-HELLER, S., MILLER, C. A., MILLER, J. W., AL-CHALABI, A., MORRIS, J. C., SHAW, C. E., MYERS, A. J., WILTFANG, J., O'BRYANT, S., OLICHNEY, J. M., ALVAREZ, V., PARISI, J. E., SINGLETON, A. B., PAULSON, H. L., COLLINGE, J., PERRY, W. R., MEAD, S., PESKIND, E., CRIBBS, D. H., ROSSOR, M., PIERCE, A., RYAN, N. S., POON, W. W., NACMIAS, B., POTTER, H., SORBI, S., QUINN, J. F., SACCHINELLI, E., RAJ, A., SPALLETTA, G., RASKIND, M., CALTAGIRONE, C., BOSSU, P., ORFEI, M. D., REISBERG, B., CLARKE, R., REITZ, C., RINGMAN, J. M., WARDEN, D., ROBERSON, E. D., WILCOCK, G., ROGAEVA, E., BRUNI, A. C., ROSEN, H. J., GALLO, M., ROSENBERG, R. N., BEN-SHLOMO, Y., SAGER, M. A., MECOCCI, P., SAYKIN, A. J., PASTOR, P., CUCCARO, M. L., VANCE, J. M., SCHNEIDER, J. A., SCHNEIDER, L. S., SLIFER, S., SEELEY, W. W., SMITH, A. V., SONNEN, J. A., SPINA, S., STERN, R. A., SWERDLOW, R. H., TANG, M., TANZI, R. E., TROJANOWSKI, J. Q., TRONCOSO, J. C., VAN DEERLIN, V. M., VAN ELDIK, L. J., VINTERS, H. V., VONSATTEL, J. P., WEINTRAUB, S., WELSH-BOHMER, K. A., WILHELMSEN, K. C., WILLIAMSON, J., WINGO, T. S., WOLTJER, R. L., WRIGHT, C. B., YU, C. E., YU, L., SABA, Y., ALZHEIMER DISEASE GENETICS, Consortium, EUROPEAN ALZHEIMER'S DISEASE, Initiative, COHORTS FOR, Heart, AGING RESEARCH IN GENOMIC EPIDEMIOLOGY, Consortium, GENETIC ENVIRONMENTAL RISK IN AD/DEFINING GENETIC, Polygenic, ENVIRONMENTAL RISK FOR ALZHEIMER'S DISEASE, Consortium, PILOTTO, A., BULLIDO, M. J., PETERS, O., CRANE, P. K., BENNETT, D., BOSCO, P., COTO, E., BOCCARDI, V., DE JAGER, P. L., LLEO, A., WARNER, N., LOPEZ, O. L., INGELSSON, M., DELOUKAS, P., CRUCHAGA, C., GRAFF, C., GWILLIAM, R., FORNAGE, M., GOATE, A. M., SANCHEZ-JUAN, P., KEHOE, P. G., AMIN, N., ERTEKIN-TANER, N., BERR, C., DEBETTE, S., LOVE, S., LAUNER, L. J., YOUNKIN, S. G., DARTIGUES, Jean-Francois, CORCORAN, C., IKRAM, M. A., DICKSON, D. W., NICOLAS, G., CAMPION, D., TSCHANZ, J., SCHMIDT, H., HAKONARSON, H., CLARIMON, J., MUNGER, R., SCHMIDT, R., FARRER, L. A., VAN BROECKHOVEN, C., M, C. O' Donovan, DESTEFANO, A. L., JONES, L., HAINES, J. L., DELEUZE, J. F., OWEN, M. J., GUDNASON, V., MAYEUX, R., ESCOTT-PRICE, V., PSATY, B. M., RAMIREZ, A., WANG, L. S., RUIZ, A., VAN DUIJN, C. M., HOLMANS, P. A., SESHADRI, S., WILLIAMS, J., AMOUYEL, P., SCHELLENBERG, G. D., LAMBERT, J. C., and PERICAK-VANCE, M. A.

Published
2019

17. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates A beta, tau, immunity and lipid processing

Author

KUNKLE, B. W., GRENIER-BOLEY, B., SIMS, R., BIS, J. C., DAMOTTE, V., NAJ, A. C., BOLAND, A., VRONSKAYA, M., VAN DER LEE, S. J., AMLIE-WOLF, A., BELLENGUEZ, C., FRIZATTI, A., CHOURAKI, V., MARTIN, E. R., SLEEGERS, K., BADARINARAYAN, N., JAKOBSDOTTIR, J., HAMILTON-NELSON, K. L., MORENO-GRAU, S., OLASO, R., RAYBOULD, R., CHEN, Y., KUZMA, A. B., HILTUNEN, M., MORGAN, T., AHMAD, S., VARDARAJAN, B. N., EPELBAUM, J., HOFFMANN, P., BOADA, M., BEECHAM, G. W., GARNIER, J. G., HAROLD, D., FITZPATRICK, A. L., VALLADARES, O., MOUTET, M. L., GERRISH, A., SMITH, A. V., QU, L., BACQ, D., DENNING, N., JIAN, X., ZHAO, Y., DEL ZOMPO, M., FOX, N. C., CHOI, S. H., MATEO, I., HUGHES, J. T., ADAMS, H. H., MALAMON, J., SANCHEZ-GARCIA, F., PATEL, Y., BRODY, J. A., DOMBROSKI, B. A., NARANJO, M. C. D., DANIILIDOU, M., EIRIKSDOTTIR, G., MUKHERJEE, S., WALLON, D., UPHILL, J., ASPELUND, T., CANTWELL, L. B., GARZIA, F., GALIMBERTI, D., HOFER, E., BUTKIEWICZ, M., FIN, B., SCARPINI, E., SARNOWSKI, C., BUSH, W. S., MESLAGE, S., KORNHUBER, J., WHITE, C. C., SONG, Y., BARBER, R. C., ENGELBORGHS, S., SORDON, S., VOIJNOVIC, D., ADAMS, P. M., VANDENBERGHE, R., MAYHAUS, M., CUPPLES, L. A., ALBERT, M. S., DE DEYN, P. P., GU, W., HIMALI, J. J., BEEKLY, D., SQUASSINA, A., HARTMANN, A. M., ORELLANA, A., BLACKER, D., RODRIGUEZ-RODRIGUEZ, E., LOVESTONE, S., GARCIA, M. E., DOODY, R. S., MUNOZ-FERNADEZ, C., SUSSAMS, R., LIN, H., FAIRCHILD, T. J., BENITO, Y. A., HOLMES, C., KARAMUJIC-COMIC, H., FROSCH, M. P., THONBERG, H., MAIER, W., ROSCHUPKIN, G., GHETTI, B., GIEDRAITIS, V., KAWALIA, A., LI, S., HUEBINGER, R. M., KILANDER, L., MOEBUS, S., HERNANDEZ, I., KAMBOH, M. I., BRUNDIN, R., TURTON, J., YANG, Q., KATZ, M. J., CONCARI, L., LORD, J., BEISER, A. S., KEENE, C. D., HELISALMI, S., KLOSZEWSKA, I., KUKULL, W. A., KOIVISTO, A. M., LYNCH, A., TARRAGA, L., LARSON, E. B., HAAPASALO, A., LAWLOR, B., MOSLEY, T. H., LIPTON, R. B., SOLFRIZZI, V., GILL, M., LONGSTRETH, W. T. Jr., MONTINE, T. J., FRISARDI, V., DIEZ-FAIREN, M., RIVADENEIRA, F., PETERSEN, R. C., DERAMECOURT, V., ALVAREZ, I., SALANI, F., CIARAMELLA, A., BOERWINKLE, E., REIMAN, E. M., FIEVET, N., ROTTER, J. I., REISCH, J. S., HANON, O., CUPIDI, C., ANDRE UITTERLINDEN, A. G., ROYALL, D. R., DUFOUIL, Carole, MALETTA, R. G., DE ROJAS, I., SANO, M., BRICE, A., CECCHETTI, R., GEORGE-HYSLOP, P. S., RITCHIE, K., TSOLAKI, M., TSUANG, D. W., DUBOIS, B., CRAIG, D., WU, C. K., SOININEN, H., AVRAMIDOU, D., ALBIN, R. L., FRATIGLIONI, L., GERMANOU, A., APOSTOLOVA, L. G., KELLER, L., KOUTROUMANI, M., ARNOLD, S. E., PANZA, F., GKATZIMA, O., ASTHANA, S., HANNEQUIN, D., WHITEHEAD, P., ATWOOD, C. S., CAFFARRA, P., HAMPEL, H., QUINTELA, I., CARRACEDO, A., LANNFELT, L., RUBINSZTEIN, D. C., BARNES, L. L., PASQUIER, F., FROLICH, L., BARRAL, S., MCGUINNESS, B., BEACH, T. G., JOHNSTON, J. A., BECKER, J. T., PASSMORE, P., BIGIO, E. H., SCHOTT, J. M., BIRD, T. D., WARREN, J. D., BOEVE, B. F., LUPTON, M. K., BOWEN, J. D., PROITSI, P., BOXER, A., POWELL, J. F., BURKE, J. R., KAUWE, J. S. K., BURNS, J. M., MANCUSO, M., BUXBAUM, J. D., BONUCCELLI, U., CAIRNS, N. J., MCQUILLIN, A., CAO, C., LIVINGSTON, G., CARLSON, C. S., BASS, N. J., CARLSSON, C. M., HARDY, J., CARNEY, R. M., BRAS, J., CARRASQUILLO, M. M., GUERREIRO, R., ALLEN, M., CHUI, H. C., FISHER, E., MASULLO, C., CROCCO, E. A., DECARLI, C., BISCEGLIO, G., DICK, M., MA, L., DUARA, R., GRAFF-RADFORD, N. R., EVANS, D. A., HODGES, A., FABER, K. M., SCHERER, M., FALLON, K. B., RIEMENSCHNEIDER, M., FARDO, D. W., HEUN, R., FARLOW, M. R., KOLSCH, H., FERRIS, S., LEBER, M., FOROUD, T. M., HEUSER, I., GALASKO, D. R., GIEGLING, I., GEARING, M., HULL, M., GESCHWIND, D. H., GILBERT, J. R., MORRIS, J., GREEN, R. C., MAYO, K., GROWDON, J. H., FEULNER, T., HAMILTON, R. L., HARRELL, L. E., DRICHEL, D., HONIG, L. S., CUSHION, T. D., HUENTELMAN, M. J., HOLLINGWORTH, P., HULETTE, C. M., HYMAN, B. T., MARSHALL, R., JARVIK, G. P., MEGGY, A., ABNER, E., MENZIES, G. E., JIN, L. W., LEONENKO, G., REAL, L. M., JUN, G. R., BALDWIN, C. T., GROZEVA, D., KARYDAS, A., RUSSO, G., KAYE, J. A., KIM, R., JESSEN, F., KOWALL, N. W., VELLAS, B., KRAMER, J. H., VARDY, E., LAFERLA, F. M., JOCKEL, K. H., LAH, J. J., DICHGANS, M., LEVERENZ, J. B., MANN, D., LEVEY, A. I., PICKERING-BROWN, S., LIEBERMAN, A. P., KLOPP, N., LUNETTA, K. L., WICHMANN, H. E., LYKETSOS, C. G., MORGAN, K., MARSON, D. C., BROWN, K., MARTINIUK, F., MEDWAY, C., MASH, D. C., NOTHEN, M. M., MASLIAH, E., HOOPER, N. M., MCCORMICK, W. C., DANIELE, A., MCCURRY, S. M., BAYER, A., MCDAVID, A. N., GALLACHER, J., MCKEE, A. C., VAN DEN BUSSCHE, H., MESULAM, M., BRAYNE, C., MILLER, B. L., RIEDEL-HELLER, S., MILLER, C. A., MILLER, J. W., AL-CHALABI, A., MORRIS, J. C., SHAW, C. E., MYERS, A. J., WILTFANG, J., O'BRYANT, S., OLICHNEY, J. M., ALVAREZ, V., PARISI, J. E., SINGLETON, A. B., PAULSON, H. L., COLLINGE, J., PERRY, W. R., MEAD, S., PESKIND, E., CRIBBS, D. H., ROSSOR, M., PIERCE, A., RYAN, N. S., POON, W. W., NACMIAS, B., POTTER, H., SORBI, S., QUINN, J. F., SACCHINELLI, E., RAJ, A., SPALLETTA, G., RASKIND, M., CALTAGIRONE, C., BOSSU, P., ORFEI, M. D., REISBERG, B., CLARKE, R., REITZ, C., SMITH, A. D., RINGMAN, J. M., WARDEN, D., ROBERSON, E. D., WILCOCK, G., ROGAEVA, E., BRUNI, A. C., ROSEN, H. J., GALLO, M., ROSENBERG, R. N., BEN-SHLOMO, Y., SAGER, M. A., MECOCCI, P., SAYKIN, A. J., PASTOR, P., CUCCARO, M. L., VANCE, J. M., SCHNEIDER, J. A., SCHNEIDER, L. S., SLIFER, S., SEELEY, W. W., SMITH, A. G., SONNEN, J. A., SPINA, S., STERN, R. A., SWERDLOW, R. H., TANG, M., TANZI, R. E., TROJANOWSKI, J. Q., TRONCOSO, J. C., VAN DEERLIN, V. M., VAN ELDIK, L. J., VINTERS, H. V., VONSATTEL, J. P., WEINTRAUB, S., WELSH-BOHMER, K. A., WILHELMSEN, K. C., WILLIAMSON, J., WINGO, T. S., WOLTJER, R. L., WRIGHT, C. B., YU, C. E., YU, L., SABA, Y., ALZHEIMER DISEASE GENETICS, Consortium, EUROPEAN ALZHEIMER'S DISEASE, Initiative, COHORTS FOR, Heart, AGING RESEARCH IN GENOMIC EPIDEMIOLOGY, Consortium, GENETIC ENVIRONMENTAL RISK IN AD/DEFINING GENETIC, Polygenic, ENVIRONMENTAL RISK FOR ALZHEIMER'S DISEASE, Consortium, PILOTTO, A., BULLIDO, M. J., PETERS, O., CRANE, P. K., BENNETT, D., BOSCO, P., COTO, E., BOCCARDI, V., DE JAGER, P. L., LLEO, A., WARNER, N., LOPEZ, O. L., INGELSSON, M., DELOUKAS, P., CRUCHAGA, C., GRAFF, C., GWILLIAM, R., FORNAGE, M., GOATE, A. M., SANCHEZ-JUAN, P., KEHOE, P. G., AMIN, N., ERTEKIN-TANER, N., BERR, C., DEBETTE, Stephanie, LOVE, S., LAUNER, L. J., YOUNKIN, S. G., DARTIGUES, Jean-Francois, CORCORAN, C., IKRAM, M. A., DICKSON, D. W., NICOLAS, G., CAMPION, D., TSCHANZ, J., SCHMIDT, H., HAKONARSON, H., CLARIMON, J., MUNGER, R., SCHMIDT, R., FARRER, L. A., VAN BROECKHOVEN, C., M, C. O' Donovan, DESTEFANO, A. L., JONES, L., HAINES, J. L., DELEUZE, J. F., OWEN, M. J., GUDNASON, V., MAYEUX, R., ESCOTT-PRICE, V., PSATY, B. M., RAMIREZ, A., WANG, L. S., RUIZ, A., VAN DUIJN, C. M., HOLMANS, P. A., SESHADRI, S., WILLIAMS, J., AMOUYEL, P., SCHELLENBERG, G. D., LAMBERT, J. C., PERICAK-VANCE, M. A., Epidemiology, Internal Medicine, Neurology, Radiology & Nuclear Medicine, Amsterdam Reproduction & Development (AR&D), Clinical sciences, Pathologic Biochemistry and Physiology, 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, Medizin, Gene Expression, genetics [Alzheimer Disease], Genome-wide association study, methods [Genome-Wide Association Study], SEPIA, Genome-wide association studies, genetic meta-analysis, 0302 clinical medicine, genetics [Immunity], genetics [Amyloid beta-Peptides], genetics, tau, genetics [Genetic Predisposition to Disease], new risk loci, Aβ, Genetics, Medicine(all), 0303 health sciences, medicine.diagnostic_test, Alzheimer's disease, Lipids, 3. Good health, Settore MED/26 - NEUROLOGIA, VINTAGE, Female, Amyloid beta, methods [Genetic Testing], Tau protein, lipid processing, tau Proteins, genetics [Genetic Loci], Biology, Article, FR, 03 medical and health sciences, Alzheimer Disease, ddc:570, genetics [Haplotypes], medicine, Genetic predisposition, Humans, Dementia, Genetic Predisposition to Disease, Genetic Testing, LOAD, genetics [Lipids], Risk factor, immunity, Aged, 030304 developmental biology, Genetic testing, Amyloid beta-Peptides, Lipid Metabolism, medicine.disease, Gene expression, genetics [tau Proteins], Haplotypes, Genetic Loci, Case-Control Studies, genetics [Lipid Metabolism], genome-wide association studies, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, 030217 neurology & neurosurgery, Genome-Wide Association Study, dementia
Abstract

Risk for late-onset Alzheimers disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimers or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimers disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 ׫2009»10−7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

Published
2019
Full Text
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18. Mapping disparities in education across low- and middle-income countries

Author

Local Burden of Disease Educational Attainment Collaborators

Abstract

Educational attainment is an important social determinant of maternal, newborn, and child health 1-3 . As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting 4-6 . The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness 7,8 ; however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health 9-11 . Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but-to our knowledge-no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries 12-14 . By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations.

Published
2020

20. MRI phenotypes of the brain are related to future stroke and mortality in patients with manifest arterial disease: The SMART-MR study

Author

Researchgr. Neuroradiologie, Brain, MS Radiologie, Circulatory Health, Cancer, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 7a, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Second Manifestations of ARTerial Disease (SMART) Study Group., Researchgr. Neuroradiologie, Brain, MS Radiologie, Circulatory Health, Cancer, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 7a, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, and Second Manifestations of ARTerial Disease (SMART) Study Group.

Published
2020

21. Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy

Author

Bodossaki Foundation, AXA Research Fund, Hellenic Foundation for Research and Innovation, European Commission, Fondazione Umberto Veronesi, Japan Society for the Promotion of Science, Telethon Italia, Ministero della Salute, Ministero dell'Istruzione, dell'Università e della Ricerca, Fondation Leducq, European Research Council, General Secretariat of Research and Technology (Greece), International Foundation for Optic Nerve Disease, Palikaras, Konstantinos[0000-0001-6992-5560], Naon, Deborah [0000-0002-9726-4664], Quintana-Cabrera, Ruben [0000-0002-0601-349X], Tavernarakis, Nektarios [0000-0002-5253-1466], Scorrano, Luca [0000-0002-8515-8928], Zaninello, Marta, Palikaras, Konstantinos, Naon, Deborah, Iwata, keiko, Herkenne, Stephanie, Quintana-Cabrera, Ruben, Semenzato, Martina, Grespi, Francesca, Ross-Cisneros, Fred N., Carelli, Valerio, Sadun, Alfredo A., Tavernarakis, Nektarios, Scorrano, Luca, Bodossaki Foundation, AXA Research Fund, Hellenic Foundation for Research and Innovation, European Commission, Fondazione Umberto Veronesi, Japan Society for the Promotion of Science, Telethon Italia, Ministero della Salute, Ministero dell'Istruzione, dell'Università e della Ricerca, Fondation Leducq, European Research Council, General Secretariat of Research and Technology (Greece), International Foundation for Optic Nerve Disease, Palikaras, Konstantinos[0000-0001-6992-5560], Naon, Deborah [0000-0002-9726-4664], Quintana-Cabrera, Ruben [0000-0002-0601-349X], Tavernarakis, Nektarios [0000-0002-5253-1466], Scorrano, Luca [0000-0002-8515-8928], Zaninello, Marta, Palikaras, Konstantinos, Naon, Deborah, Iwata, keiko, Herkenne, Stephanie, Quintana-Cabrera, Ruben, Semenzato, Martina, Grespi, Francesca, Ross-Cisneros, Fred N., Carelli, Valerio, Sadun, Alfredo A., Tavernarakis, Nektarios, and Scorrano, Luca

Abstract

In autosomal dominant optic atrophy (ADOA), caused by mutations in the mitochondrial cristae biogenesis and fusion protein optic atrophy 1 (Opa1), retinal ganglion cell (RGC) dysfunction and visual loss occur by unknown mechanisms. Here, we show a role for autophagy in ADOA pathogenesis. In RGCs expressing mutated Opa1, active 5’ AMP-activated protein kinase (AMPK) and its autophagy effector ULK1 accumulate at axonal hillocks. This AMPK activation triggers localized hillock autophagosome accumulation and mitophagy, ultimately resulting in reduced axonal mitochondrial content that is restored by genetic inhibition of AMPK and autophagy. In C. elegans, deletion of AMPK or of key autophagy and mitophagy genes normalizes the axonal mitochondrial content that is reduced upon mitochondrial dysfunction. In conditional, RGC specific Opa1-deficient mice, depletion of the essential autophagy gene Atg7 normalizes the excess autophagy and corrects the visual defects caused by Opa1 ablation. Thus, our data identify AMPK and autophagy as targetable components of ADOA pathogenesis.

Published
2020

22. Non-coding variability at the APOE locus contributes to the Alzheimer’s risk

Author

Fu, A.K.Y., Kwok, T.C.Y., Mok, V.C.T., Ip, F.C., Sullivan, P.F., Mullapudi, N., Hardy, J., Chen, Y., Giusti-Rodríguez, P., Alzheimer's Disease Neuroimaging Initiative, Li, Y., Mok, K.Y., Ip, N.Y., Zhou, X., and Guo, Q.

Abstract

Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.

Published
2019
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23. Distribution and impact on quality of life of the pain modalities assessed by the King's Parkinson's disease pain scale

Author

Martinez-Martin, Pablo, Manuel Rojo-Abuin, Jose, Rizos, Alexandra, Rodriguez-Blazquez, Carmen, Trenkwalder, Claudia, Perkins, Lauren, Sauerbier, Anna, Odin, Per, Antonini, Angelo, Chaudhuri, Kallol Ray, International Parkinson's Disease Non-Motor Group (PDNMG), EUROPAR Study Group, King's Parkinson's Disease Pain Scale (KPPS), Parkinson's UK, National Institute for Health Research (Reino Unido), NIHR - Mental Health Biomedical Research Centre (Reino Unido), South London and Maudsley NHS Foundation Trust (Reino Unido), Imperial College London (Reino Unido), NIHR - Mental Health Biomedical Research Centre, NHS - Foundation Trust, and King ’s College London

Subjects
0301 basic medicine, Quality of life, medicine.medical_specialty, Parkinson's disease, Neurology, Disease, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, RC346-429, Pain modalities, Modalities, business.industry, Pain scale, Burning mouth syndrome, medicine.disease, 030104 developmental biology, Physical therapy, Pain catastrophizing, Neurology (clinical), Neurology. Diseases of the nervous system, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

In Parkinson’s disease, pain is a prevalent and complex symptom of diverse origin. King’s Parkinson’s disease pain scale, assesses different pain syndromes, thus allowing exploration of its differential prevalence and influence on the health-related quality of life of patients. Post hoc study 178 patients and 83 matched controls participating in the King’s Parkinson’s disease pain scale validation study were used. For determining the respective distribution, King’s Parkinson’s disease pain scale items and domains scores = 0 meant absence and ≥1 presence of the symptom. The regular scores were used for the other analyses. Health-related quality of lifewas evaluated with EQ-5D-3L and PDQ-8 questionnaires. Parkinson’s disease patients experienced more pain modalities than controls. In patients, Pain around joints (King’s Parkinson’s disease pain scale item 1) and Pain while turning in bed (item 8) were the most prevalent types of pain, whereas Burning mouth syndrome (item 11) and Pain due to grinding teeth (item 10) showed the lowest frequency. The total number of experienced pain modalities closely correlated with the PDQ-8 index, but not with other variables. For all pain types except Pain around joints (item 1) and pain related to Periodic leg movements/RLS (item 7), patients with pain had significantly worse health-related quality of life. The influence of pain, as a whole, on the health-related quality of life was not remarkable after adjustment by other variables. When the particular types of pain were considered, adjusted by sex, age, and Parkinson’s disease duration, pain determinants were different for EQ-5D-3L and PDQ-8. King’s Parkinson’s disease pain scale allows exploring the distribution of the diverse syndromic pain occurring in Parkinson’s disease and its association with health-related quality of life., Pain: Under-appreciated impact on quality of life Researchers confirm that the pain experienced by patients with Parkinson disease (PD) is a key determinant of health-related quality of life. Pain is a common non-motor symptom that is often underacknowledged and undertreated. Using data from the recently validated pain scale for PD, Pablo Martinez-Martin (Carlos III Institute of Health in Madrid, Spain) and colleagues explored the impact of specific pain modalities on patients’ quality of life. They found that patients with PD reported experiencing twice as many types of pain than controls, with pain around the joints and pain while moving in bed being the most prevalent. Furthermore, there was a close correlation between the number of experienced pain modalities and quality of life as evaluated with the PD questionnaire PDQ-8. Understanding the different types of pain in PD will aid the provision of effective pain relief and greatly improve patients’wellbeing.

Published
2017

24. Multimodal Hippocampal Subfield Grading For Alzheimer's Disease Classification

Author

Universitat Politècnica de València. Departamento de Física Aplicada - Departament de Física Aplicada, Pfizer, National Institute on Aging, EEUU, National Institutes of Health, EEUU, Agence Nationale de la Recherche, Francia, National Institute of Neurological Disorders and Stroke, EEUU, National Institute of Biomedical Imaging and Bioengineering, EEUU, Hett, Kilian, Ta, Vinh-Thong, Catheline, Gwenaelle, Tourdias, Thomas, Manjón Herrera, José Vicente, Coupé, Pierrick, Alzheimers Disease Neuroimaging Initiative, Universitat Politècnica de València. Departamento de Física Aplicada - Departament de Física Aplicada, Pfizer, National Institute on Aging, EEUU, National Institutes of Health, EEUU, Agence Nationale de la Recherche, Francia, National Institute of Neurological Disorders and Stroke, EEUU, National Institute of Biomedical Imaging and Bioengineering, EEUU, Hett, Kilian, Ta, Vinh-Thong, Catheline, Gwenaelle, Tourdias, Thomas, Manjón Herrera, José Vicente, Coupé, Pierrick, and Alzheimers Disease Neuroimaging Initiative

Abstract

[EN] Numerous studies have proposed biomarkers based on magnetic resonance imaging (MRI) to detect and predict the risk of evolution toward Alzheimer's disease (AD). Most of these methods have focused on the hippocampus, which is known to be one of the earliest structures impacted by the disease. To date, patch-based grading approaches provide among the best biomarkers based on the hippocampus. However, this structure is complex and is divided into different subfields, not equally impacted by AD. Former in-vivo imaging studies mainly investigated structural alterations of these subfields using volumetric measurements and microstructural modifications with mean diffusivity measurements. The aim of our work is to improve the current classification performances based on the hippocampus with a new multimodal patch-based framework combining structural and diffusivity MRI. The combination of these two MRI modalities enables the capture of subtle structural and microstructural alterations. Moreover, we propose to study the efficiency of this new framework applied to the hippocampal subfields. To this end, we compare the classification accuracy provided by the different hippocampal subfields using volume, mean diffusivity, and our novel multimodal patch-based grading framework combining structural and diffusion MRI. The experiments conducted in this work show that our new multimodal patch-based method applied to the whole hippocampus provides the most discriminating biomarker for advanced AD detection while our new framework applied into subiculum obtains the best results for AD prediction, improving by two percentage points the accuracy compared to the whole hippocampus.

Published
2019

25. Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders

Author

de Lange, Siemon C., Scholtens, Lianne H., van den Berg, Leonard H., Boks, Marco P., Bozzali, Marco, Cahn, Wiepke, Dannlowski, Udo, Durston, Sarah, Geuze, Elbert, van Haren, Neeltje E.M., Hillegers, Manon H.J., Koch, Kathrin, Jurado, María Ángeles, Mancini, Matteo, Marqués-Iturria, Idoia, Meinert, Susanne, Ophoff, Roel A., Reess, Tim J., Repple, Jonathan, Kahn, René S., van den Heuvel, Martijn P., Alzheimer’s Disease Neuroimaging Initiative, de Lange, Siemon C., Scholtens, Lianne H., van den Berg, Leonard H., Boks, Marco P., Bozzali, Marco, Cahn, Wiepke, Dannlowski, Udo, Durston, Sarah, Geuze, Elbert, van Haren, Neeltje E.M., Hillegers, Manon H.J., Koch, Kathrin, Jurado, María Ángeles, Mancini, Matteo, Marqués-Iturria, Idoia, Meinert, Susanne, Ophoff, Roel A., Reess, Tim J., Repple, Jonathan, Kahn, René S., van den Heuvel, Martijn P., and Alzheimer’s Disease Neuroimaging Initiative

Published
2019

26. Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders

Author

UMC Utrecht, Projectafdeling ALS, ZL Neuromusculaire Ziekten Medisch, Brain, Regenerative Medicine and Stem Cells, Onderzoeksgroep 2, Onderzoek, Ontwikkelingsstoornissen Ond., MGGZ, Onderzoeksgroep 1, Diagnostiek & Vroege Psychose Medisch, de Lange, Siemon C., Scholtens, Lianne H., van den Berg, Leonard H., Boks, Marco P., Bozzali, Marco, Cahn, Wiepke, Dannlowski, Udo, Durston, Sarah, Geuze, Elbert, van Haren, Neeltje E.M., Hillegers, Manon H.J., Koch, Kathrin, Jurado, María Ángeles, Mancini, Matteo, Marqués-Iturria, Idoia, Meinert, Susanne, Ophoff, Roel A., Reess, Tim J., Repple, Jonathan, Kahn, René S., van den Heuvel, Martijn P., Alzheimer's Disease Neuroimaging Initiative, UMC Utrecht, Projectafdeling ALS, ZL Neuromusculaire Ziekten Medisch, Brain, Regenerative Medicine and Stem Cells, Onderzoeksgroep 2, Onderzoek, Ontwikkelingsstoornissen Ond., MGGZ, Onderzoeksgroep 1, Diagnostiek & Vroege Psychose Medisch, de Lange, Siemon C., Scholtens, Lianne H., van den Berg, Leonard H., Boks, Marco P., Bozzali, Marco, Cahn, Wiepke, Dannlowski, Udo, Durston, Sarah, Geuze, Elbert, van Haren, Neeltje E.M., Hillegers, Manon H.J., Koch, Kathrin, Jurado, María Ángeles, Mancini, Matteo, Marqués-Iturria, Idoia, Meinert, Susanne, Ophoff, Roel A., Reess, Tim J., Repple, Jonathan, Kahn, René S., van den Heuvel, Martijn P., and Alzheimer's Disease Neuroimaging Initiative

Published
2019

27. Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson’s disease pathogenesis

Author

Instituto de Salud Carlos III, European Commission, Parkinson's Disease Society (UK), Ministerio de Economía y Competitividad (España), Michael J. Fox Foundation for Parkinson's Research, Fundación la Caixa, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Fundación Tatiana Pérez de Guzmán el Bueno, Generalitat de Catalunya, Carballo-Carbajal, Iria, Laguna, Ariadna, Romero-Giménez, Jordi, Cuadros, Thais, Bové, Jordi, Martinez-Vicente, Marta, Parent, Annabelle, González-Sepúlveda, Marta, Peñuelas, Nuria, Torra, Albert, Rodríguez-Galván, Beatriz, Ballabio, Andrea, Hasegawa, Takafumi, Bortolozzi, Analía, Gelpi, Ellen, Vila, Miquel, Instituto de Salud Carlos III, European Commission, Parkinson's Disease Society (UK), Ministerio de Economía y Competitividad (España), Michael J. Fox Foundation for Parkinson's Research, Fundación la Caixa, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Fundación Tatiana Pérez de Guzmán el Bueno, Generalitat de Catalunya, Carballo-Carbajal, Iria, Laguna, Ariadna, Romero-Giménez, Jordi, Cuadros, Thais, Bové, Jordi, Martinez-Vicente, Marta, Parent, Annabelle, González-Sepúlveda, Marta, Peñuelas, Nuria, Torra, Albert, Rodríguez-Galván, Beatriz, Ballabio, Andrea, Hasegawa, Takafumi, Bortolozzi, Analía, Gelpi, Ellen, and Vila, Miquel

Abstract

In Parkinson’s disease (PD) there is a selective degeneration of neuromelanin-containing neurons, especially substantia nigra dopaminergic neurons. In humans, neuromelanin accumulates with age, the latter being the main risk factor for PD. The contribution of neuromelanin to PD pathogenesis remains unknown because, unlike humans, common laboratory animals lack neuromelanin. Synthesis of peripheral melanins is mediated by tyrosinase, an enzyme also present at low levels in the brain. Here we report that overexpression of human tyrosinase in rat substantia nigra results in age-dependent production of human-like neuromelanin within nigral dopaminergic neurons, up to levels reached in elderly humans. In these animals, intracellular neuromelanin accumulation above a specific threshold is associated to an age-dependent PD phenotype, including hypokinesia, Lewy body-like formation and nigrostriatal neurodegeneration. Enhancing lysosomal proteostasis reduces intracellular neuromelanin and prevents neurodegeneration in tyrosinase-overexpressing animals. Our results suggest that intracellular neuromelanin levels may set the threshold for the initiation of PD.

Published
2019

28. Progress towards non-invasive diagnosis and follow-up of celiac disease in children; a prospective multicentre study to the usefulness of plasma I-FABP

Author

Adriaanse, Marlou P. M., Mubarak, A, Riedl, R G, Ten Kate, F J W, Damoiseaux, J G M C, Buurman, Wim A., Houwen, R H J, Vreugdenhil, A C E, Celiac Disease Study Group, Promovendi NTM, RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: DA CDL Algemeen (9), RS: NUTRIM - R4 - Gene-environment interaction, Surgery, Kindergeneeskunde, MUMC+: MA Medische Staf Kindergeneeskunde (9), RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, and RS: NUTRIM - R1 - Metabolic Syndrome

Subjects
Male, Pediatrics, Biopsy, Disease, Gastroenterology, Coeliac disease, 0302 clinical medicine, HLA Antigens, Intestine, Small, Prospective Studies, Prospective cohort study, Child, chemistry.chemical_classification, DAMAGE, Multidisciplinary, medicine.diagnostic_test, biology, Prognosis, 030220 oncology & carcinogenesis, Child, Preschool, Medicine, 030211 gastroenterology & hepatology, lipids (amino acids, peptides, and proteins), Female, Antibody, SENSITIVITY, medicine.medical_specialty, Genotype, Science, VILLOUS ATROPHY, Fatty Acid-Binding Proteins, Article, 03 medical and health sciences, Diet, Gluten-Free, Internal medicine, medicine, Humans, Autoantibodies, GLUTEN, business.industry, Non invasive, Infant, ADULTS, medicine.disease, Gluten, GENE, Molecular Typing, Celiac Disease, chemistry, MARKER, ANTIBODIES, biology.protein, Gluten free, business, Biomarkers, Follow-Up Studies
Abstract

This prospective study investigates whether measurement of plasma intestinal-fatty acid binding protein (I-FABP), a sensitive marker for small intestinal epithelial damage, improves non-invasive diagnosing of celiac disease (CD), and whether I-FABP levels are useful to evaluate mucosal healing in patients on a gluten-free diet (GFD). Ninety children with elevated tTG-IgA titres and HLA-DQ2/DQ8 positivity were included (study group). Duodenal biopsies were taken, except in those fulfilling the ESPGHAN criteria. Plasma I-FABP levels and tTG-IgA titres were assessed sequentially during six months of follow-up. Eighty children with normal tTG-IgA titres served as control group. In 61/90 (67.8%) of the children in the study group an increased I-FABP level was found; in all these children CD diagnosis was confirmed. Interestingly, in 14/30 (46.7%) children with slightly elevated tTG-IgA titres (

Published
2017

29. Erratum : Grams ME, Sang Y, Ballew SH, et al, for the Chronic Kidney Disease Prognosis Consortium. Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int. 2018;93:1442–1451 (Kidney International (2018) 93(6) (1442–1451), (S0085253818300978) (10.1016/j.kint.2018.01.009))

Author

Astor, Brad, Appel, Lawrence J., Levin, Adeera, Tang, Mila, Djurdjev, Ognjenka, Navaneethan, Sankar D., Jolly, Stacey E., Schold, Jesse D., Nally, Joseph V., Wheeler, David C., Emberson, Jonathan, Townend, John, Landray, Martin, Feldman, Harold I., Hsu, Chi yuan, Lash, James P., Kalra, Philip A., Ritchie, James P., Maharajan, Raman, Middleton, Rachel J., O'Donoghue, Donal J., Eckardt, Kai Uwe, Schneider, Markus P., Köttgen, Anna, Kronenberg, Florian, Bärthlein, Barbara, Chang, Alex R., Green, Jamie A., Kirchner, H. Lester, Ho, Kevin, Marks, Angharad, Black, Corri, Prescott, Gordon J., Fluck, Nick, Nakayama, Masaaki, Miyazaki, Mariko, Yamamoto, Tae, Yamada, Gen, Wang, Angela Yee Moon, Cheung, Sharon, Wong, Sharon, Chu, Jessie, Wu, Henry, Garg, Amit X., McArthur, Eric, Nash, Danielle M., Blankestijn, Peter J., van Zuilen, Arjan D., Visseren, Frank L.J., van der Graaf, Yolanda, Chronic Kidney Disease Prognosis Consortium, Astor, Brad, Appel, Lawrence J., Levin, Adeera, Tang, Mila, Djurdjev, Ognjenka, Navaneethan, Sankar D., Jolly, Stacey E., Schold, Jesse D., Nally, Joseph V., Wheeler, David C., Emberson, Jonathan, Townend, John, Landray, Martin, Feldman, Harold I., Hsu, Chi yuan, Lash, James P., Kalra, Philip A., Ritchie, James P., Maharajan, Raman, Middleton, Rachel J., O'Donoghue, Donal J., Eckardt, Kai Uwe, Schneider, Markus P., Köttgen, Anna, Kronenberg, Florian, Bärthlein, Barbara, Chang, Alex R., Green, Jamie A., Kirchner, H. Lester, Ho, Kevin, Marks, Angharad, Black, Corri, Prescott, Gordon J., Fluck, Nick, Nakayama, Masaaki, Miyazaki, Mariko, Yamamoto, Tae, Yamada, Gen, Wang, Angela Yee Moon, Cheung, Sharon, Wong, Sharon, Chu, Jessie, Wu, Henry, Garg, Amit X., McArthur, Eric, Nash, Danielle M., Blankestijn, Peter J., van Zuilen, Arjan D., Visseren, Frank L.J., van der Graaf, Yolanda, and Chronic Kidney Disease Prognosis Consortium

Published
2018

30. Erratum: Grams ME, Sang Y, Ballew SH, et al, for the Chronic Kidney Disease Prognosis Consortium. Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int. 2018;93:1442–1451 (Kidney International (2018) 93(6) (1442–1451), (S0085253818300978) (10.1016/j.kint.2018.01.009))

Author

MS Nefrologie, Circulatory Health, Interne Geneeskunde Vasculaire, Cardiovasculaire Epi Team 5, Astor, Brad, Appel, Lawrence J., Levin, Adeera, Tang, Mila, Djurdjev, Ognjenka, Navaneethan, Sankar D., Jolly, Stacey E., Schold, Jesse D., Nally, Joseph V., Wheeler, David C., Emberson, Jonathan, Townend, John, Landray, Martin, Feldman, Harold I., Hsu, Chi yuan, Lash, James P., Kalra, Philip A., Ritchie, James P., Maharajan, Raman, Middleton, Rachel J., O'Donoghue, Donal J., Eckardt, Kai Uwe, Schneider, Markus P., Köttgen, Anna, Kronenberg, Florian, Bärthlein, Barbara, Chang, Alex R., Green, Jamie A., Kirchner, H. Lester, Ho, Kevin, Marks, Angharad, Black, Corri, Prescott, Gordon J., Fluck, Nick, Nakayama, Masaaki, Miyazaki, Mariko, Yamamoto, Tae, Yamada, Gen, Wang, Angela Yee Moon, Cheung, Sharon, Wong, Sharon, Chu, Jessie, Wu, Henry, Garg, Amit X., McArthur, Eric, Nash, Danielle M., Blankestijn, Peter J., van Zuilen, Arjan D., Visseren, Frank L.J., van der Graaf, Yolanda, Chronic Kidney Disease Prognosis Consortium, MS Nefrologie, Circulatory Health, Interne Geneeskunde Vasculaire, Cardiovasculaire Epi Team 5, Astor, Brad, Appel, Lawrence J., Levin, Adeera, Tang, Mila, Djurdjev, Ognjenka, Navaneethan, Sankar D., Jolly, Stacey E., Schold, Jesse D., Nally, Joseph V., Wheeler, David C., Emberson, Jonathan, Townend, John, Landray, Martin, Feldman, Harold I., Hsu, Chi yuan, Lash, James P., Kalra, Philip A., Ritchie, James P., Maharajan, Raman, Middleton, Rachel J., O'Donoghue, Donal J., Eckardt, Kai Uwe, Schneider, Markus P., Köttgen, Anna, Kronenberg, Florian, Bärthlein, Barbara, Chang, Alex R., Green, Jamie A., Kirchner, H. Lester, Ho, Kevin, Marks, Angharad, Black, Corri, Prescott, Gordon J., Fluck, Nick, Nakayama, Masaaki, Miyazaki, Mariko, Yamamoto, Tae, Yamada, Gen, Wang, Angela Yee Moon, Cheung, Sharon, Wong, Sharon, Chu, Jessie, Wu, Henry, Garg, Amit X., McArthur, Eric, Nash, Danielle M., Blankestijn, Peter J., van Zuilen, Arjan D., Visseren, Frank L.J., van der Graaf, Yolanda, and Chronic Kidney Disease Prognosis Consortium

Published
2018

31. 22 Years of predictive testing for Huntington's disease: the experience of the UK Huntington's Prediction Consortium

Author

Sheharyar S Baig, Mark Strong, Elisabeth Rosser, Nicola V Taverner, Ruth Glew, Zosia Miedzybrodzka, Angus Clarke, David Craufurd, UK Huntington's Disease Prediction Consortium, and Oliver W Quarrell

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Population, Disease, 030105 genetics & heredity, Article, 03 medical and health sciences, Huntington's disease, Predictive Value of Tests, Internal medicine, medicine, Prevalence, Genetics, Humans, Genetic Testing, education, Predictive testing, Genetics (clinical), Genetic testing, education.field_of_study, medicine.diagnostic_test, business.industry, Public health, Middle Aged, medicine.disease, United Kingdom, Huntington Disease, Predictive value of tests, Mutation, Medical genetics, Female, business, Corrigendum
Abstract

Huntington's disease (HD) is a progressive neurodegenerative condition. At-risk individuals have accessed predictive testing via direct mutation testing since 1993. The UK Huntington's Prediction Consortium has collected anonymised data on UK predictive tests, annually, from 1993 to 2014: 9407 predictive tests were performed across 23 UK centres. Where gender was recorded, 4077 participants were male (44.3%) and 5122 were female (55.7%). The median age of participants was 37 years. The most common reason for predictive testing was to reduce uncertainty (70.5%). Of the 8441 predictive tests on individuals at 50% prior risk, 4629 (54.8%) were reported as mutation negative and 3790 (44.9%) were mutation positive, with 22 (0.3%) in the database being uninterpretable. Using a prevalence figure of 12.3 × 10(-5), the cumulative uptake of predictive testing in the 50% at-risk UK population from 1994 to 2014 was estimated at 17.4% (95% CI: 16.9-18.0%). We present the largest study conducted on predictive testing in HD. Our findings indicate that the vast majority of individuals at risk of HD (80%) have not undergone predictive testing. Future therapies in HD will likely target presymptomatic individuals; therefore, identifying the at-risk population whose gene status is unknown is of significant public health value.

Published
2016

32. Identification of common variants associated with human hippocampal and intracranial volumes

Author

Stein, Jason L, Medland, Sarah E, Bernard, Manon, Nauck, Matthias, Nöthen, Markus M., Olvera, Rene L, Pandolfo, Massimo, Pike, G Bruce, Puls, Ralf, Reinvang, Ivar, Rentería, Miguel E, Rietschel, Marcella, Roffman, Joshua L, Brown, Andrew A, Royle, Natalie A, Rujescu, Dan, Savitz, Jonathan, Schnack, Hugo G, Schnell, Knut, Seiferth, Nina, Smith, Colin, Steen, Vidar M, Valdés Hernández, Maria C, Van den Heuvel, Martijn, Cannon, Dara M, van der Wee, Nic J, Van Haren, Neeltje E M, Veltman, Joris A, Völzke, Henry, Walker, Robert, Westlye, Lars T, Whelan, Christopher D, Agartz, Ingrid, Boomsma, Dorret I, Cavalleri, Gianpiero L, Chakravarty, M Mallar, Dale, Anders M, Djurovic, Srdjan, Drevets, Wayne C, Hagoort, Peter, Hall, Jeremy, Heinz, Andreas, Jack, Clifford R, Foroud, Tatiana M, Le Hellard, Stephanie, Macciardi, Fabio, Christoforou, Andrea, Montgomery, Grant W, Poline, Jean Baptiste, Porteous, David J, Sisodiya, Sanjay M, Starr, John M, Sussmann, Jessika, Toga, Arthur W, Veltman, Dick J, Walter, Henrik, Weiner, Michael W, Domin, Martin, Initiative, Alzheimer's Disease Neuroimaging, Consortium, EPIGEN, Consortium, IMAGEN, Group, Saguenay Youth Study, Bis, Joshua C, Ikram, M Arfan, Smith, Albert V, Gudnason, Vilmundur, Tzourio, Christophe, Vernooij, Meike W, Grimm, Oliver, Launer, Lenore J, DeCarli, Charles, Seshadri, Sudha, Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology, Andreassen, Ole A, Apostolova, Liana G, Bastin, Mark E, Blangero, John, Brunner, Han G, Buckner, Randy L, Hollinshead, Marisa, Cichon, Sven, Coppola, Giovanni, de Zubicaray, Greig I, Deary, Ian J, Donohoe, Gary, de Geus, Eco J C, Espeseth, Thomas, Fernández, Guillén, Glahn, David C, Grabe, Hans J, Holmes, Avram J, Hardy, John, Hulshoff Pol, Hilleke E, Jenkinson, Mark, Kahn, René S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Meyer-Lindenberg, Andreas, Morris, Derek W, Homuth, Georg, Müller-Myhsok, Bertram, Nichols, Thomas E, Ophoff, Roel A, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W, Potkin, Steven G, Sämann, Philipp G, Saykin, Andrew J, Schumann, Gunter, Vasquez, Alejandro Arias, Hottenga, Jouke-Jan, Smoller, Jordan W, Wardlaw, Joanna M, Weale, Michael E, Martin, Nicholas G, Franke, Barbara, Wright, Margaret J, Thompson, Paul M, Consortium, Enhancing Neuro Imaging Genetics through Meta-Analysis, Weiner, Michael, Aisen, Paul, Langan, Camilla, Petersen, Ronald, Jagust, William, Trojanowki, John Q, Beckett, Laurel, Green, Robert C, Morris, John, Liu, Enchi, Lopez, Lorna M, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Hansell, Narelle K, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Hwang, Kristy S, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Kim, Sungeun, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Laje, Gonzalo, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lee, Phil H, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Liu, Xinmin, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Carroll, Maria, Loth, Eva, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Hibar, Derrek P, Lourdusamy, Anbarasu, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, Mattingsdal, Morten, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Coleman, R Edward, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Hardy, Peter, Mohnke, Sebastian, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Mulnard, Ruth A, Thai, Gaby, Maniega, Susana Muñoz, Mc-Adams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Nho, Kwangsik, Lah, James J, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Lu, Po H, Bartzokis, George, Silverman, Daniel H S, Graff-Radford, Neill R, Nugent, Allison C, Parfitt, Francine, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, van Dyck, Christopher H, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, O'Brien, Carol, Bergman, Howard, Hosei, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Papmeyer, Martina, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristina, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Pütz, Benno, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Ramasamy, Adaikalavan, Taylor, Joy L, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Senstad, Rudy E, Rasmussen, Jerod, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Bwayo, Salome K, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Rijpkema, Mark, Olichney, John, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Risacher, Shannon L, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Roddey, J Cooper, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Santulli, Robert B, Schwartz, Eben S, Sink, Kaycee M, Rose, Emma J, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Ryten, Mina, Miller, Bruce L, Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Finger, Elizabeth, Rachinsky, Irina, Drost, Dick, Cavalleri, Gianpiero, Alhusaini, Saud, Delanty, Norman, Whelan, Christopher, Sisodiya, Sanjay, Kasperaviciute, Dalia, Matarin, Mar, Depondt, Chantal, Goldstein, David B, Heinzen, Erin L, Shianna, Kevin, Sprooten, Emma, Radtke, Rodney, Ottmann, Ruth, Sergievsky, G. H., Schumann, G., Conrod, P., Reed, L., Barker, G., Williams, S., Loth, E., Struve, M., Strengman, Eric, Lourdusamy, A., Cattrell, A., Nymberg, C., Topper, L., Smith, L., Havatzias, S., Stueber, K., Mallik, C., Stacey, D., Wong, C Peng, Teumer, Alexander, Werts, H., Andrew, C., Desrivieres, S., Heinz, A., Gallinat, J., Häke, I., Ivanov, N., Klär, A., Reuter, J., Winkler, Anderson M, Trabzuni, Daniah, Palafox, C., Hohmann, C., Schilling, C., Lüdemann, K., Romanowski, A., Ströhle, A., Wolff, E., Rapp, M., Ittermann, B., Brühl, R., Turner, Jessica, Ihlenfeld, A., Walaszek, B., Schubert, F., Garavan, H., Connolly, C., Jones, J., Lalor, E., McCabe, E., Ní Shiothcháin, A., Whelan, R., van Eijk, Kristel, Spanagel, R., Leonardi-Essmann, F., Sommer, W., Flor, H., Vollstaedt-Klein, S., Nees, F., Banaschewski, T., Poustka, L., Steiner, S., Mann, K., van Erp, Theo G M, Buehler, M., Rietschel, M., Stolzenburg, E., Schmal, C., Schirmbeck, F., Paus, T., Gowland, P., Heym, N., Lawrence, C., Newman, C., van Tol, Marie-Jose, Pausova, Z., Smolka, M., Huebner, T., Ripke, S., Mennigen, E., Muller, K., Ziesch, V., Büchel, C., Bromberg, U., Fadai, T., Wittfeld, Katharina, Lueken, L., Yacubian, J., Finsterbusch, J., Martinot, J. L., Artiges, E., Bordas, N., de Bournonville, S., Bricaud, Z., Gollier Briand, F., Lemaitre, H., Wolf, Christiane, Massicotte, J., Miranda, R., Paillère Martinot, M. L., Penttilä, J., Poline, J. B., Barbot, A., Schwartz, Y., Lalanne, C., Frouin, V., Thyreau, B., Woudstra, Saskia, Dalley, J., Mar, A., Robbins, T., Subramaniam, N., Theobald, D., Richmond, N., de Rover, M., Molander, A., Jordan, E., Robinson, E., Aleman, Andre, Hipolata, L., Moreno, M., Arroyo, M., Stephens, D., Ripley, T., Crombag, H., Pena, Y., Lathrop, M., Zelenika, D., Heath, S., Lanzerath, D., Heinrichs, B., Spranger, T., Fuchs, B., Speiser, C., Resch, F., Haffner, J., Parzer, P., Brunner, R., Klaassen, A., Toro, Roberto, Almasy, Laura, Klaassen, I., Constant, P., Mignon, X., Thomsen, T., Zysset, S., Vestboe, A., Ireland, J., Rogers, J., Binder, Elisabeth B, Chakravarty, Mallar, Smith, Albert Vernon, van der Lijn, Fedde, Crivello, Fabrice, Fornage, Myriam, Shulman, Joshua M, Brohawn, David G, Schmidt, Helena, Srikanth, Velandai, Schuur, Maaike, Yu, Lei, Choi, Seung-Hoan, Sigurdsson, Sigurdur, Verhaaren, Benjamin F J, DeStefano, Anita L, Lambert, Jean-Charles, Cantor, Rita M, Struchalin, Maksim, Stankovich, Jim, Ibrahim-Verbaas, Carla A, Fleischman, Debra, Zijdenbos, Alex, den Heijer, Tom, Mazoyer, Bernard, Coker, Laura H, Enzinger, Christian, Danoy, Patrick, Carless, Melanie A, Amin, Najaf, Arfanakis, Konstantinos, van Buchem, Mark A, de Bruijn, Renée F A G, Beiser, Alexa, Dufouil, Carole, Huang, Juebin, Cavalieri, Margherita, Thomson, Russell, Niessen, Wiro J, Corvin, Aiden, Chibnik, Lori B, Gislason, Gauti K, Hofman, Albert, Pikula, Aleksandra, Amouyel, Philippe, Freeman, Kevin B, Phan, Thanh G, Oostra, Ben A, Nalls, Michael A, Uitterlinden, Andre G, Czisch, Michael, Au, Rhoda, Elbaz, Alexis, Beare, Richard J, van Swieten, John C, Lopez, Oscar, Harris, Tamara B, Chouraki, Vincent, Breteler, Monique M B, De Jager, Philip L, Becker, James T, Curran, Joanne E, Knopman, David, Fazekas, Franz, Wolf, Philip A, van der Lugt, Aad, Longstreth, W. T., Brown, Mathew A, Bennett, David A, van Duijn, Cornelia M, Davies, Gail, Mosley, Thomas H, Schmidt, Reinhold, de Almeida, Marcio A A, Appel, Katja, Duggirala, Ravi, Dyer, Thomas D, Erk, Susanne, Fagerness, Jesen, Fox, Peter T, Freimer, Nelson B, Gill, Michael, Göring, Harald H H, Bartecek, Richard, Hagler, Donald J, Hoehn, David, Holsboer, Florian, Hoogman, Martine, Hosten, Norbert, Jahanshad, Neda, Johnson, Matthew P, Kent, Jack W, Kochunov, Peter, Bergmann, Ørjan, Lancaster, Jack L, Lawrie, Stephen M, Liewald, David C, Mandl, René, Mattheisen, Manuel, Meisenzahl, Eva, Melle, Ingrid, Moses, Eric K, Mühleisen, Thomas W, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Queensland Institute of Medical Research, Radboud University Medical Center [Nijmegen], Yale University School of Medicine, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Universität Greifswald - University of Greifswald, Universität Heidelberg [Heidelberg], University Medical Center [Utrecht], University of Oslo (UiO), University of Toronto, National University of Ireland [Galway] (NUI Galway), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], University of Bergen (UiB), Harvard University [Cambridge], VU University Amsterdam, University of Edinburgh, Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], National Institutes of Health [Bethesda] (NIH), Department of Forensic and Neurodevelopmental Sciences, King‘s College London, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Georgia State University, University System of Georgia (USG), Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), Leiden University Medical Center (LUMC), Dundee Technopole, CXR Biosciences Ltd, University of Groningen [Groningen], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Department of Genetics, Southwest Foundation for Biomedical Research, Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, The University of Texas Health Science Center at Houston (UTHealth), Center for Neurobehavioral Genetics, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Computer Science, Durham University, Laboratoire des symbioses tropicales et méditerranéennes (UMR LSTM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of California, Institute of Neurology [London], University College of London [London] (UCL), University of California [San Francisco] (UCSF), Department of Medicine, University of Washington [Seattle], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre Émile Durkheim (CED), Sciences Po Bordeaux - Institut d'études politiques de Bordeaux (IEP Bordeaux)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Salermo, Università degli Studi di Salerno (UNISA), School of Psychology, University of Queensland, University of Queensland [Brisbane], Hartford Hospital, Lancaster University, Centre for Advanced Imaging, McConnell Brain Imaging Centre (MNI), McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Stanley Center for Psychiatric Research, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Faculteit Medische Wetenschappen/UMCG, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Biological Psychology, Neuroscience Campus Amsterdam - Brain Imaging, EMGO+ - Mental Health, EPIGEN Consortium, IMAGENConsortium, Saguenay Youth Study Group, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium, Psychiatry, NCA - Brain Imaging, EMGO - Mental health, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Virology, Epidemiology, Clinical Chemistry, Erasmus MC other, Radiology & Nuclear Medicine, University of California (UC)-University of California (UC), Yale School of Medicine [New Haven, Connecticut] (YSM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg] = Heidelberg University, Harvard University, Vrije Universiteit Amsterdam [Amsterdam] (VU), University of California [Irvine] (UC Irvine), Universiteit Leiden, University of California (UC), University of California [San Francisco] (UC San Francisco), Università degli Studi di Salerno = University of Salerno (UNISA), University of Iceland [Reykjavik], McGill University, University of Bergen (UIB), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Bijvoet Center of Biomolecular Research, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, UMR5116, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and McGill University-McGill University

Subjects
Netherlands Twin Register (NTR), Pathology, 110 012 Social cognition of verbal communication, [SDV]Life Sciences [q-bio], Hippocampus, Genome-wide association study, DCN PAC - Perception action and control, Hippocampal formation, physiopathology [Brain], Bioinformatics, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, TEMPORAL-LOBE EPILEPSY, 110 014 Public activities, Renal disorder [IGMD 9], 0303 health sciences, medicine.diagnostic_test, Translational research Immune Regulation [ONCOL 3], Brain, Human brain, Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3], ALZHEIMERS-DISEASE, medicine.anatomical_structure, Brain size, genetics [Chromosomes, Human, Pair 12], genetics [Polymorphism, Single Nucleotide], Biomarker (medicine), NA+/H+ EXCHANGER, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Genetic Markers, medicine.medical_specialty, 110 000 Neurocognition of Language, DCN MP - Plasticity and memory, A neurocomputational model for the Processing of Linguistic Utterances based on the Unification-Space architecture [110 007 PLUS], BRAIN VOLUME, UNIFIED APPROACH, 110 013 Binding and the MUC-model, Neuroimaging, Biology, GENOTYPE IMPUTATION, Polymorphism, Single Nucleotide, Article, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], 03 medical and health sciences, AUTOMATED SEGMENTATION, Meta-Analysis as Topic, SDG 3 - Good Health and Well-being, ddc:570, FUNCTIONAL IMPLICATIONS, Genetics, medicine, Humans, GENOME-WIDE ASSOCIATION, 030304 developmental biology, Chromosomes, Human, Pair 12, Magnetic resonance imaging, Genetic Loci, physiopathology [Hippocampus], 110 009 The human brain and Chinese prosody, Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6], HUMAN HEIGHT, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Contains fulltext : 108202.pdf (Publisher’s version ) (Closed access) Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 x 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 x 10(-7)). 01 mei 2012

Published
2012
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33. Progress towards non-invasive diagnosis and follow-up of celiac disease in children: a prospective multicentre study to the usefulness of plasma I-FABP

Author

MDL onderzoek 1, Pathologie Pathologen staf, MDL patientenzorg, Child Health, Adriaanse, Marlou P. M., Mubarak, A, Riedl, R G, Ten Kate, F J W, Damoiseaux, J G M C, Buurman, Wim A., Houwen, R H J, Vreugdenhil, A C E, Celiac Disease Study Group, MDL onderzoek 1, Pathologie Pathologen staf, MDL patientenzorg, Child Health, Adriaanse, Marlou P. M., Mubarak, A, Riedl, R G, Ten Kate, F J W, Damoiseaux, J G M C, Buurman, Wim A., Houwen, R H J, Vreugdenhil, A C E, and Celiac Disease Study Group

Published
2017

34. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

Author

Chambers, John C., Zhang, Weihua, Sehmi, Joban, Li, Xinzhong, Wass, Mark N., Van der Harst, Pim, Holm, Hilma, Sanna, Serena, Kavousi, Maryam, Baumeister, Sebastian E., Coin, Lachlan J., Deng, Guohong, Gieger, Christian, Heard-Costa, Nancy L., Hottenga, Jouke-Jan, Kühnel, Brigitte, Kumar, Vinod, Lagou, Vasiliki, Liang, Liming, Luan, Jian'an, Vidal, Pedro Marques, Mateo Leach, Irene, O'Reilly, Paul F., Peden, John F., Rahmioglu, Nilufer, Soininen, Pasi, Speliotes, Elizabeth K., Yuan, Xin, Thorleifsson, Gudmar, Alizadeh, Behrooz Z., Atwood, Larry D., Borecki, Ingrid B., Brown, Morris J., Charoen, Pimphen, Cucca, Francesco, Das, Debashish, de Geus, Eco J. C., Dixon, Anna L., Döring, Angela, Ehret, Georg, Eyjolfsson, Gudmundur I., Farrall, Martin, Forouhi, Nita G., Friedrich, Nele, Goessling, Wolfram, Gudbjartsson, Daniel F., Harris, Tamara B., Hartikainen, Anna-Liisa, Heath, Simon, Hirschfield, Gideon M., Hofman, Albert, Homuth, Georg, Hyppönen, Elina, Janssen, Harry L. A., Johnson, Toby, Kangas, Antti J., Kema, Ido P., Kühn, Jens P., Lai, Sandra, Lathrop, Mark, Lerch, Markus M., Li, Yun, Liang, T. Jake, Lin, Jing-Ping, Loos, Ruth J. F., Martin, Nicholas G., Moffatt, Miriam F., Montgomery, Grant W., Munroe, Patricia B., Musunuru, Kiran, Nakamura, Yusuke, O'Donnell, Christopher J., Olafsson, Isleifur, Penninx, Brenda W., Pouta, Anneli, Prins, Bram P., Prokopenko, Inga, Puls, Ralf, Ruokonen, Aimo, Savolainen, Markku J., Schlessinger, David, Schouten, Jeoffrey N. L., Seedorf, Udo, Sen-Chowdhry, Srijita, Siminovitch, Katherine A., Smit, Johannes H., Spector, Timothy D., Tan, Wenting, Teslovich, Tanya M., Tukiainen, Taru, Uitterlinden, Andre G., Van der Klauw, Melanie M., Vasan, Ramachandran S., Wallace, Chris, Wallaschofski, Henri, Wichmann, H-Erich, Willemsen, Gonneke, Würtz, Peter, Xu, Chun, Yerges-Armstrong, Laura M., Alcohol Genome-wide Association Consortium, Diabetes Genetics Replication, Meta-analyses Study, Genetic Investigation of Anthropometric Traits Consortium, Global Lipids Genetics Consortium, Genetics of Liver Disease Consortium, International Consortium for Blood Pressure, Meta-analyses of Glucose, Insulin-Related Traits Consortium, Abecasis, Goncalo R., Ahmadi, Kourosh R., Boomsma, Dorret I., Caulfield, Mark, Cookson, William O., van Duijn, Cornelia M., Froguel, Philippe, Matsuda, Koichi, McCarthy, Mark I., Meisinger, Christa, Mooser, Vincent, Pietiläinen, Kirsi H., Schumann, Gunter, Snieder, Harold, Sternberg, Michael J. E., Stolk, Ronald P., Thomas, Howard C., Thorsteinsdottir, Unnur, Uda, Manuela, Waeber, Gérard, Wareham, Nicholas J., Waterworth, Dawn M., Watkins, Hugh, Whitfield, John B., Witteman, Jacqueline C. M., Wolffenbuttel, Bruce H. R., Fox, Caroline S., Ala-Korpela, Mika, Stefansson, Kari, Vollenweider, Peter, Völzke, Henry, Schadt, Eric E., Scott, James, Järvelin, Marjo-Riitta, Elliott, Paul, and Kooner, Jaspal S.

Published
2011
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35. Genome-wide association identifies three new susceptibility loci for Paget's disease of bone

Author

Albagha, O, Wani, S., Visconti, M., Alonso, N., Goodman, K., Genetic Determinants Of Paget's Disease Consortium., (gdpd), Verbruggen, Leon, and Internal Medicine Specializations

Subjects
Asian Continental Ancestry Group, PDB, chromosomes, Genetic, Paget's disease, Osteitis Deformans, bone
Abstract

Paget's disease of bone (PDB) is a common disorder characterized by focal abnormalities of bone remodeling. We previously identified variants at the CSF1, OPTN and TNFRSF11A loci as risk factors for PDB by genome-wide association study. Here we extended this study, identified three new loci and confirmed their association with PDB in 2,215 affected individuals (cases) and 4,370 controls from seven independent populations. The new associations were with rs5742915 within PML on 15q24 (odds ratio (OR) = 1.34, P = 1.6 × 10(-14)), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 × 10(-11)) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 × 10(-10)). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 × 10(-17)) with PDB. These seven loci explained ?13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.

Published
2011

36. Clustering of target organ damage increases mortality after acute coronary syndromes in patients with arterial hypertension

Author

Cordero A, Morillas P, Bertomeu-Gonzalez V, Quiles J, Mazon P, Guindo J, Soria F, Llacer A, Lekuona I, Gonzalez-Juanatey JR, Bertomeu V, and Prevalence of Peripheral Arterial Disease in Patients with Acute Coronary Syndro

Subjects
ankle-brachial index, prognosis, acute coronary syndrome
Abstract

The impact of target organ damage (TOD) clustering in hypertensive patients with established cardiovascular disease has not been clearly defined. Multicentre, observational and prospective study of 1054 consecutive patients with acute coronary syndromes (ACSs). The objective was describing the impact of TOD on first-year mortality. Ankle-brachial index (ABI), left ventricular hypertrophy and renal dysfunction were assessed during hospital stay. Hypertensive patients accounted for 80% of the cohort and had slightly higher mean age, higher prevalence of risk factors, previous cardiovascular disease and TOD. During follow-up, mean time 387.9 (7.2) days and median 382 (364.0-430.0) days, mortality rate tended to be higher in hypertensive patients (6.1 versus 3.5%; P = 0.16). Cox regression survival analysis identified pathological ABI as the only TOD independently associated with mortality. When assessed globally, the presence of at least one TOD predicted mortality only in patients with hypertension and differences in mortality rate appeared very early in the follow-up. A linear increase in mortality rate was observed with the clustering of TOD: 2.0%, if no TOD was present, 7.6% in one TOD, 11.1% in two TODs and 20.0%, if three TODs were present. An increased risk in the combined end point of ischaemic events was observed in hypertensive patients without TOD (odds ratio (OR): 3.18; 95% confidence interval (CI): 1.31-7.70; P = 0.01) and was still higher in patients with hypertension and TOD (OR: 4.61; 95% CI: 1.90-11.80; P < 0.01). TOD predicts mortality and ischaemic events of hypertensive patients after ACS. Journal of Human Hypertension (2011) 25, 600-607; doi:10.1038/jhh.2010.109; published online 16 December 2010

Published
2011

37. World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010

Author

LS IRAS VPH MBR (microbiol.risico sch.), Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA2, Havelaar, Arie H, Kirk, Martyn D, Torgerson, Paul R, Gibb, Herman J, Hald, Tine, Lake, Robin J, Praet, Nicolas, Bellinger, David C, de Silva, Nilanthi R, Gargouri, Neyla, Speybroeck, Niko, Cawthorne, Amy, Mathers, Colin, Stein, Claudia, Angulo, Frederick J, Devleesschauwer, Brecht, World Health Organization Foodborne Disease Burden Epidemiology Reference Group, LS IRAS VPH MBR (microbiol.risico sch.), Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA2, Havelaar, Arie H, Kirk, Martyn D, Torgerson, Paul R, Gibb, Herman J, Hald, Tine, Lake, Robin J, Praet, Nicolas, Bellinger, David C, de Silva, Nilanthi R, Gargouri, Neyla, Speybroeck, Niko, Cawthorne, Amy, Mathers, Colin, Stein, Claudia, Angulo, Frederick J, Devleesschauwer, Brecht, and World Health Organization Foodborne Disease Burden Epidemiology Reference Group

Published
2015

38. Mapping child growth failure across low- and middle-income countries

Author

Kinyoki,, D.K, Osgood-Zimmerman,, A.E, Pickering,, B.V., Ahmadi, Keivan, Local Burden of Disease Child Growth Failure Collaborators, Kassebaum,, N.J, Hay,, S.I, Kinyoki,, D.K, Osgood-Zimmerman,, A.E, Pickering,, B.V., Ahmadi, Keivan, Local Burden of Disease Child Growth Failure Collaborators, Kassebaum,, N.J, and Hay,, S.I

Abstract

Childhood malnutrition is associated with high morbidity and mortality globally. Undernourished children are more likely to experience cognitive, physical, and metabolic developmental impairments that can lead to later cardiovascular disease, reduced intellectual ability and school attainment, and reduced economic productivity in adulthood. Child growth failure (CGF), expressed as stunting, wasting, and underweight in children under fve years of age (0–59 months), is a specifc subset of undernutrition characterized by insufcient height or weight against age-specifc growth reference standards. The prevalence of stunting, wasting, or underweight in children under fve is the proportion of children with a height-for-age, weight-for-height, or weight-for-age z-score, respectively, that is more than two standard deviations below the World Health Organization’s median growth reference standards for a healthy population. Subnational estimates of CGF report substantial heterogeneity within countries, but are available primarily at the frst administrative level (for example, states or provinces); the uneven geographical distribution of CGF has motivated further calls for assessments that can match the local scale of many public health programmes. Building from our previous work mapping CGF in Africa, here we provide the frst, to our knowledge, mapped highspatial-resolution estimates of CGF indicators from 2000 to 2017 across 105 low- and middle-income countries (LMICs), where 99% of afected children live, aggregated topolicy-relevant frst and second (for example, districts or counties) administrativelevel units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the ambitious World Health Organization Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and progress exist across and within countries; our maps identify high-prevalence areas even within nations othe

39. Mapping routine measles vaccination in low- and middle-income countries

Author

Vaccine Coverage Collaborators including, Local Burden of Disease, Ahmadi, Keivan, Vaccine Coverage Collaborators including, Local Burden of Disease, and Ahmadi, Keivan

Abstract

The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1,2,3,4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5,6,7,8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2 pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.

40. Hippocampal transcriptome-wide association study and pathway analysis of mitochondrial solute carriers in Alzheimer’s disease

Author

Jing Tian, Kun Jia, Tienju Wang, Lan Guo, Zhenyu Xuan, Elias K. Michaelis, Russell H. Swerdlow, Alzheimer’s Disease Neuroimaging Initiative, and Heng Du

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract The etiopathogenesis of late-onset Alzheimer’s disease (AD) is increasingly recognized as the result of the combination of the aging process, toxic proteins, brain dysmetabolism, and genetic risks. Although the role of mitochondrial dysfunction in the pathogenesis of AD has been well-appreciated, the interaction between mitochondrial function and genetic variability in promoting dementia is still poorly understood. In this study, by tissue-specific transcriptome-wide association study (TWAS) and further meta-analysis, we examined the genetic association between mitochondrial solute carrier family (SLC25) genes and AD in three independent cohorts and identified three AD-susceptibility genes, including SLC25A10, SLC25A17, and SLC25A22. Integrative analysis using neuroimaging data and hippocampal TWAS-predicted gene expression of the three susceptibility genes showed an inverse correlation of SLC25A22 with hippocampal atrophy rate in AD patients, which outweighed the impacts of sex, age, and apolipoprotein E4 (ApoE4). Furthermore, SLC25A22 downregulation demonstrated an association with AD onset, as compared with the other two transcriptome-wide significant genes. Pathway and network analysis related hippocampal SLC25A22 downregulation to defects in neuronal function and development, echoing the enrichment of SLC25A22 expression in human glutamatergic neurons. The most parsimonious interpretation of the results is that we have identified AD-susceptibility genes in the SLC25 family through the prediction of hippocampal gene expression. Moreover, our findings mechanistically yield insight into the mitochondrial cascade hypothesis of AD and pave the way for the future development of diagnostic tools for the early prevention of AD from a perspective of precision medicine by targeting the mitochondria-related genes.

Published
2024
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41. Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-β 42/40 positivity

Author

Jung-Min Pyun, Young Ho Park, Young Chul Youn, Min Ju Kang, Kyu Hwan Shim, Jae-Won Jang, Jihwan You, Kwangsik Nho, SangYun Kim, and the Alzheimer’s Disease Neuroimaging Initiative

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Various plasma biomarkers for amyloid-β (Aβ) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma Aβ42/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as Aβ plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma Aβ42/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET−/plasma−, PET−/plasma+, PET+/plasma−, PET+/plasma+) using Alzheimer’s Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET−/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET−/plasma+ showed intermediate changes between PET−/plasma− and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma− represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma Aβ42/40 than IA-Elc. IA-Elc showed more plasma Aβ42/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET−/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.

Published
2024
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42. A multimodal deep learning approach for the prediction of cognitive decline and its effectiveness in clinical trials for Alzheimer’s disease

Author

Caihua Wang, Hisateru Tachimori, Hiroyuki Yamaguchi, Atsushi Sekiguchi, Yuanzhong Li, Yuichi Yamashita, and for Alzheimer’s Disease Neuroimaging Initiative

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Alzheimer’s disease is one of the most important health-care challenges in the world. For decades, numerous efforts have been made to develop therapeutics for Alzheimer’s disease, but most clinical trials have failed to show significant treatment effects on slowing or halting cognitive decline. Among several challenges in such trials, one recently noticed but unsolved is biased allocation of fast and slow cognitive decliners to treatment and placebo groups during randomization caused by the large individual variation in the speed of cognitive decline. This allocation bias directly results in either over- or underestimation of the treatment effect from the outcome of the trial. In this study, we propose a stratified randomization method using the degree of cognitive decline predicted by an artificial intelligence model as a stratification index to suppress the allocation bias in randomization and evaluate its effectiveness by simulation using ADNI data set.

Published
2024
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43. Higher immune-related gene expression in major depression is independent of CRP levels: results from the BIODEP study

Author

Luca Sforzini, Annamaria Cattaneo, Clarissa Ferrari, Lorinda Turner, Nicole Mariani, Daniela Enache, Caitlin Hastings, Giulia Lombardo, Maria A. Nettis, Naghmeh Nikkheslat, Courtney Worrell, Zuzanna Zajkowska, Melisa Kose, Nadia Cattane, Nicola Lopizzo, Monica Mazzelli, Linda Pointon, Philip J. Cowen, Jonathan Cavanagh, Neil A. Harrison, Declan Jones, Wayne C. Drevets, Valeria Mondelli, Edward T. Bullmore, Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium, and Carmine M. Pariante

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Compelling evidence demonstrates that some individuals suffering from major depressive disorder (MDD) exhibit increased levels of inflammation. Most studies focus on inflammation-related proteins, such as serum or plasma C-reactive protein (CRP). However, the immune-related modifications associated with MDD may be not entirely captured by CRP alone. Analysing mRNA gene expression levels, we aimed to identify broader molecular immune-related phenotypes of MDD. We examined 168 individuals from the non-interventional, case–control, BIODEP study, 128 with a diagnosis of MDD and 40 healthy controls. Individuals with MDD were further divided according to serum high-sensitivity (hs)CRP levels (n = 59 with CRP 3 mg/L). We isolated RNA from whole blood and performed gene expression analyses using RT-qPCR. We measured the expression of 16 immune-related candidate genes: A2M, AQP4, CCL2, CXCL12, CRP, FKBP5, IL-1-beta, IL-6, ISG15, MIF, GR, P2RX7, SGK1, STAT1, TNF-alpha and USP18. Nine of the 16 candidate genes were differentially expressed in MDD cases vs. controls, with no differences between CRP-based groups. Only CRP mRNA was clearly associated with serum CRP. In contrast, plasma (proteins) IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-16, IL-17A, IFN-gamma and TNF-alpha, and neutrophils counts, were all differentially regulated between CRP-based groups (higher in CRP >3 vs. CRP

Published
2023
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44. Posttraumatic stress symptom severity predicts cognitive decline beyond the effect of Alzheimer’s disease biomarkers in Veterans

Author

Sarah Prieto, Kate E. Nolan, Jena N. Moody, Scott M. Hayes, Jasmeet P. Hayes, and for the Department of Defense Alzheimer’s Disease Neuroimaging Initiative

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Chronic stress is a risk factor for dementia but whether it explains unique variance in cognitive decline in older adults above Alzheimer’s disease (AD) biomarkers is unknown. In a preclinical cohort of Vietnam Veterans, we examined the relationship between posttraumatic stress disorder (PTSD) symptom severity, AD biomarkers of beta-amyloid (Aβ) and tau, and change in cognitive performance on two widely-used screeners, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Analyses indicated that PTSD symptom severity was associated with a greater decline on the MMSE (p

Published
2023
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45. Distinct spatiotemporal subtypes of amyloid deposition are associated with diverging disease profiles in cognitively normal and mild cognitive impairment individuals

Author

Yuqing Sun, Yuxin Zhao, Ke Hu, Meng Wang, Yong Liu, Bing Liu, and for the Alzheimer’s Disease Neuroimaging Initiative

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract We aimed to investigate the relationship between spatiotemporal changes of amyloid deposition and Alzheimer’s disease (AD) profiles in cognitively normal (CN) and those with mild cognitive impairment (MCI). Using a data-driven method and amyloid-PET data, we identified and validated two subtypes in two independent datasets (discovery dataset: N = 548, age = 72.4 ± 6.78, 49% female; validation dataset: N = 348, age = 74.9 ± 8.16, 47% female) from the Alzheimer’s Disease Neuroimaging Initiative across a range of individuals who were CN or had MCI. The two subtypes showed distinct regional progression patterns and presented distinct genetic, clinical and biomarker characteristics. The cortex-priority subtype was more likely to show typical clinical syndromes of symptomatic AD and vice versa. Furthermore, the regional progression patterns were associated with clinical and biomarker profiles. In sum, our findings suggest that the spatiotemporal variants of amyloid depositions are in close association with disease trajectories; these findings may provide insight into the disease monitoring and enrollment of therapeutic trials in AD.

Published
2023
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46. Prediction model for short-term mortality after palliative radiotherapy for patients having advanced cancer: a cohort study from routine electronic medical data

Author

Chuk Kwan Ng, Hollis Luk, Aray Wong, Shing Fung Lee, Miguel Angel Luque-Fernandez, Frank Chi Sing Wong, [Lee,SF, Luk,H, Wong,A, Ng,CK, Wong,FCS] Department of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, Hong Kong. [Luque-Fernandez,MA] Department of Non-Communicable Disease and Cancer Epidemiology, Institute de Investigacion Biosanitaria de Granada (ibs.GRANADA), University of Granada, Granada, Spain. [Luque-Fernandez,MA] Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK., and There was no explicit funding for the development of this project. MALF is supported by a Miguel Servet I Investigator Award (grant CP17/00206 EU-FEDER) from the National Institute of Health, Carlos III (ISCIII), Madrid, Spain. His funders had no role in the study design, data collection, dataanalysis, data interpretation, or writing of the report.

Subjects
Male, medicine.medical_treatment, lcsh:Medicine, Logistic regression, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Palliative Care [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Palliative radiotherapy, Risk Factors, Neoplasms, Odds Ratio, Electronic Health Records, 030212 general & internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], lcsh:Science, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Cancer, Multidisciplinary, Palliative Care, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Prognosis, Cuidados paliativos, Neoplasias, Oncology, Outcomes research, 030220 oncology & carcinogenesis, Female, Cohort study, medicine.medical_specialty, Estudios de cohortes, Check Tags::Male [Medical Subject Headings], Article, 03 medical and health sciences, Radioterapia, Prediction model, Internal medicine, medicine, Humans, Mortality, Lung cancer, Aged, Radiotherapy, business.industry, lcsh:R, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, medicine.disease, Confidence interval, Radiation therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Records as Topic::Medical Records::Medical Records Systems, Computerized::Electronic Health Records [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Mortalidad, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], lcsh:Q, business
Abstract

We developed a predictive score system for 30-day mortality after palliative radiotherapy by using predictors from routine electronic medical record. Patients with metastatic cancer receiving first course palliative radiotherapy from 1 July, 2007 to 31 December, 2017 were identified. 30-day mortality odds ratios and probabilities of the death predictive score were obtained using multivariable logistic regression model. Overall, 5,795 patients participated. Median follow-up was 39.6 months (range, 24.5–69.3) for all surviving patients. 5,290 patients died over a median 110 days, of whom 995 (17.2%) died within 30 days of radiotherapy commencement. The most important mortality predictors were primary lung cancer (odds ratio: 1.73, 95% confidence interval: 1.47–2.04) and log peripheral blood neutrophil lymphocyte ratio (odds ratio: 1.71, 95% confidence interval: 1.52–1.92). The developed predictive scoring system had 10 predictor variables and 20 points. The cross-validated area under curve was 0.81 (95% confidence interval: 0.79–0.82). The calibration suggested a reasonably good fit for the model (likelihood-ratio statistic: 2.81, P = 0.094), providing an accurate prediction for almost all 30-day mortality probabilities. The predictive scoring system accurately predicted 30-day mortality among patients with stage IV cancer. Oncologists may use this to tailor palliative therapy for patients.

Published
2020
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47. The impact of increasing levels of blood C-reactive protein on the inflammatory loci SPI1 and CD33 in Alzheimer’s disease

Author

Jinghan Huang, Qiushan Tao, Ting Fang Alvin Ang, John Farrell, Congcong Zhu, Yixuan Wang, Thor D. Stein, Kathryn L. Lunetta, Joseph Massaro, Jesse Mez, Rhoda Au, Lindsay A. Farrer, Wei Qiao Qiu, Xiaoling Zhang, and For the Alzheimer’s Disease Neuroimaging Initiative

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Apolipoprotein ε4 (APOE ε4) is the most significant genetic risk factor for late-onset Alzheimer’s disease (AD). Elevated blood C-reactive protein (CRP) further increases the risk of AD for people carrying the APOE ε4 allele. We hypothesized that CRP, as a key inflammatory element, could modulate the impact of other genetic variants on AD risk. We selected ten single nucleotide polymorphisms (SNPs) in reported AD risk loci encoding proteins related to inflammation. We then tested the interaction effects between these SNPs and blood CRP levels on AD incidence using the Cox proportional hazards model in UK Biobank (n = 279,176 white participants with 803 incident AD cases). The five top SNPs were tested for their interaction with different CRP cutoffs for AD incidence in the Framingham Heart Study (FHS) Generation 2 cohort (n = 3009, incident AD = 156). We found that for higher concentrations of serum CRP, the AD risk increased for SNP genotypes in 3 AD-associated genes (SPI1, CD33, and CLU). Using the Cox model in stratified genotype analysis, the hazard ratios (HRs) for the association between a higher CRP level (≥10 vs.

Published
2022
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48. Polygenic resilience scores capture protective genetic effects for Alzheimer’s disease

Author

Jiahui Hou, Jonathan L. Hess, Nicola Armstrong, Joshua C. Bis, Benjamin Grenier-Boley, Ida K. Karlsson, Ganna Leonenko, Katya Numbers, Eleanor K. O’Brien, Alexey Shadrin, Anbupalam Thalamuthu, Qiong Yang, Ole A. Andreassen, Henry Brodaty, Margaret Gatz, Nicole A. Kochan, Jean-Charles Lambert, Simon M. Laws, Colin L. Masters, Karen A. Mather, Nancy L. Pedersen, Danielle Posthuma, Perminder S. Sachdev, Julie Williams, the Alzheimer’s Disease Neuroimaging Initiative, Chun Chieh Fan, Stephen V. Faraone, Christine Fennema-Notestine, Shu-Ju Lin, Valentina Escott-Price, Peter Holmans, Sudha Seshadri, Ming T. Tsuang, William S. Kremen, and Stephen J. Glatt

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.

Published
2022
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49. Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus

Author

Donal Bisanzio, Thomas W. Scott, G. R. William Wint, T. Alex Perkins, Nicole Davis Weaver, Lucas Earl, Laurie B. Marczak, Erik Wetter, Hongjie Yu, Shengjie Lai, Dingdong Yi, Simon I. Hay, Wim Van Bortel, Cedric Marsboom, Francis Schaffner, Giovanini E. Coelho, David M. Pigott, Jane P. Messina, Xin Lu, Robert C. Reiner, Linus Bengtsson, Andrew J. Tatem, David L. Smith, Chester G. Moore, Shreya Shirude, Qiyong Liu, Peter A. Jones, Kimberly J. Johnson, Roberta G. Carvalho, John S. Brownstein, Moritz U. G. Kraemer, Oliver J. Brady, Nuno R. Faria, Louis Lambrechts, Nick Golding, Marius Gilbert, Heinrich H. Nax, Guy Hendrickx, Oliver G. Pybus, Simon Cauchemez, Catherine Linard, University of Oxford [Oxford], Boston Children's Hospital, Harvard Medical School [Boston] (HMS), University of Washington [Seattle], London School of Hygiene and Tropical Medicine (LSHTM), Université libre de Bruxelles (ULB), Fonds National de la Recherche Scientifique [Bruxelles] (FNRS), Harvard University [Cambridge], University of Nottingham, UK (UON), Eck Institute for Global Health, University of Notre Dame [Indiana] (UND), Fudan University [Shanghai], University of Southampton, Flowminder Foundation, Central South University [Changsha], National University of Defense Technology [China], Southwestern University of Finance and Economics [Chengdu, China], Waen Associates Ltd, Pan American Health Organization [Washington] (PAHO), Ministry of Health [Brasília, Brazil], European Centre for Disease Prevention and Control (ECDC), Institute of Tropical Medicine [Antwerp] (ITM), Egis Avia (FRANCE), Francis Schaffner Consultancy, Colorado State University [Fort Collins] (CSU), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Karolinska Institutet [Stockholm], Stockholm School of Economics (SSE), Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Namur [Namur] (UNamur), University of California [Davis] (UC Davis), University of California, Chinese Center for Disease Control and Prevention, Shandong University, University of Melbourne, The authors thank S. Ray for providing comments during the revision process. M.U.G.K. acknowledges funding from the Society in Science, The Branco Weiss Fellowship, administered by the ETH Zurich. M.U.G.K. also acknowledges funding from the Training Grant from the National Institute of Child Health and Human Development (T32HD040128). M.U.G.K., S.I.H., J.P.M., N.G., O.J.B. and G.R.W.W. acknowledge funding from the International Research Consortium on Dengue Risk Assessment Management and Surveillance (IDAMS, European Commission 7th Framework Programme no. 21893). O.B.J. was funded by a Sir Henry Wellcome Fellowship funded by the Wellcome Trust (grant number 206471/Z/17/Z) and a grant from the Bill and Melinda Gates Foundation (OP1183567). S.I.H. received a grant from the Research for Health in Humanitarian Crises (R2HC) Programme, managed by Enhancing Learning and Research for Humanitarian Assistance (ELRHA, no. 13468), which also supported M.U.G.K. and N.G. The R2HC programme aims to improve health outcomes by strengthening the evidence base for public health interventions in humanitarian crises. The £8 million R2HC programme is funded equally by the Wellcome Trust and Department of International Development (DFiD), with ELRHA overseeing the programme’s execution and management. S.I.H. was also funded by a Senior Research Fellowship from the Wellcome Trust (no. 95066) and grants from the Bill & Melinda Gates Foundation (OPP1106023, OPP1093011, OPP1132415 and OPP1159934). This study was made possible by the support of the American people through the US Agency for International Development Emerging Pandemic Threats Program-2 PREDICT-2 (Cooperative Agreement number AID-OAA-A-14-00102), which also supported M.U.G.K. J.S.B. is supported by the National Library of Medicine of the National Institutes of Health (R01LM010812 and R01LM011965), which also supports M.U.G.K. D.L.S. is funded by the National Institutes of Health and National Institute of Allergy and Infectious Diseases (no. U10AI089674). H.H.N. was funded by the European Commission through the European Research Council Advanced Investigator Grant ‘Momentum’ 324247. L.L. received funding from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID), the French Agence Nationale de la Recherche (grant ANR-16-CE35-0004), the City of Paris Emergence(s) programme in Biomedical Research, and the European Union’s Horizon 2020 research and innovation programme under ZikaPLAN grant agreement No. 734584. S.C. received funding from the AXA Research Fund, the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (Grant ANR-10-LABX-62-IBEID), the Models of Infectious Disease Agent Study of the National Institute of General Medical Sciences, the INCEPTION project (PIA/ANR-16-CONV-0005), and the European Union’s Horizon 2020 research and innovation programme under ZIKAlliance grant agreement No 734548. N.G. is supported by a University of Melbourne McKenzie fellowship. W.V.B., G.H. and F.S. acknowledge funding from VBORNET and VectorNet, an ECDC and EFSA-funded project (no. ECDC/09/018 and OC/EFSA/AHAW/2013/02), and thank all contributing VBORNET and VectorNet experts for data sharing. T.W.S., R.C.R. and L.L. received funding from the National Institutes of Health Program Project grant (no. P01 AI098670). X.L. is supported by the Natural Science Foundation of China (71771213, 71522014, 71725001, 91846301 and 71790615). This work was also partially supported by the European Union’s Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement no. 734548., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CE35-0004,MOSQUIBIOTA,Contribution de la diversité bactérienne intestinale à la capacité vectorielle d'Aedes aegypti(2016), European Project: 734548,ZIKAlliance(2016), European Project: 324247,EC:FP7:ERC,ERC-2012-ADG_20120411,MOMENTUM(2013), European Project: 281803,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,IDAMS(2011), University of Oxford, Harvard University, European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and University of California (UC)

Subjects
Microbiology (medical), Microbiologie et protistologie [parasitologie hum. et anim.], Aedes albopictus, Arbovirus Infections, Immunology, Aedes aegypti, medicine.disease_cause, Applied Microbiology and Biotechnology, Arbovirus, Microbiology, Article, Dengue fever, Zika virus, 03 medical and health sciences, Genetics, medicine, Chikungunya, 030304 developmental biology, Aedes, 0303 health sciences, biology, 030306 microbiology, Ecology, virus diseases, Cell Biology, biology.organism_classification, medicine.disease, 3. Good health, Microbiologie et protistologie [entomologie,phytoparasitolog.], Geography, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Infectious diseases
Abstract

The global population at risk from mosquito-borne diseases—including dengue, yellow fever, chikungunya and Zika—is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus. The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally., 0, SCOPUS: ar.j, SCOPUS: er.j, info:eu-repo/semantics/published

Published
2019
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50. APOE-ε4 modulates the association among plasma Aβ42/Aβ40, vascular diseases, neurodegeneration and cognitive decline in non-demented elderly adults

Author

Dai Shi, Siwei Xie, Anqi Li, Qingyong Wang, Hongbo Guo, Ying Han, Huaxi Xu, Wen-Biao Gan, Lei Zhang, Tengfei Guo, and for the Alzheimer’s Disease Neuroimaging Initiative

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Including apolipoprotein E-ε4 (APOE-ε4) status and older age into consideration may increase the accuracy of plasma Aβ42/Aβ40 detecting Aβ+ individuals, but the rationale behind this remains to be fully understood. Besides, both Aβ pathology and vascular diseases are related to neurodegeneration and cognitive decline, but it is still not fully understood how APOE-ε4 modulates these relationships. In this study, we examined 241 non-demented Alzheimer’s Disease Neuroimaging Initiative participants to investigate the associations among age, white matter hyperintensities (WMH), hypertension, hyperlipidemia, body mass index (BMI), plasma Aβ42/Aβ40 measured by liquid chromatography tandem mass spectrometry, and 18F-florbetapir Aβ PET as well as their prediction of longitudinal adjusted hippocampal volume (aHCV) and cognition in APOE-ε4 carriers and non-carriers. We found older age predicted faster WMH increase (p = 0.024) and cortical Aβ accumulation (p = 0.043) in APOE-ε4 non-carriers only, whereas lower plasma Aβ42/Aβ40 predicted faster cortical Aβ accumulation (p

Published
2022
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