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6 results on '"Primary Hlth Care"'

1. Residual normal B-cell profiles in monoclonal B-cell lymphocytosis versus chronic lymphocytic leukemia

Author

Criado, I., Blanco, E., Rodriguez-Caballero, A., Alcoceba, M., Contreras, T., Gutierrez, M.L., Romero, A., Fernandez-Navarro, P., Gonzalez, M., Solano, F., Gomez, C., Perez-Andres, M., Dongen, J.J.M. van, Almeida, J., Orfao, A., EuroFlow PID Grp, Primary Hlth Care Grp Salamanca, Red Temática de Investigación Cooperativa en Cáncer (España), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), and Junta de Castilla y León

Subjects
Male, Cancer Research, Chronic lymphocytic leukaemia, Chronic lymphocytic leukemia, Lymphocytosis, Brief Communication, 03 medical and health sciences, 0302 clinical medicine, Text mining, medicine, Humans, B cell, Aged, B-Lymphocytes, B cells, business.industry, Hematology, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Monoclonal B-cell lymphocytosis, Female, business, 030215 immunology
Abstract

© The Author(s) 2018., Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, which is characterized by the accumulation of mature CD5+/CD20lo/CD23+ clonal B-cells in peripheral blood (PB), bone marrow (BM), and other lymphoid tissues [1]. Currently, it is well-established that CLL is systematically preceded by a pre-leukemic stage, known as monoclonal B-cell lymphocytosis (MBL) [2]; MBL includes both low-count (MBLlo) and high-count MBL (MBLhi), depending on the number of PB clonal B-cells (70 y) [4, 5]. The biological and clinical significance of CLL-like clonal B-cells in PB of otherwise healthy individuals (MBLlo) has not been fully elucidated [6,7,8]. Recently, we have reported a very low rate of transformation of MBLlo to MBLhi/CLL, after 7 years of follow-up [8]. In contrast, we found a higher frequency of deaths in MBLlo subjects vs. age- and sex-matched non-MBL healthy adults from the same geographical area; among the former subjects, infection was an overrepresented cause of death (21% vs. 2%, respectively) [8]. This is in line with previous studies showing an ≈3-fold increased risk of infection in both MBLhi and CLL patients, in whom infections also represent a major cause of death [9, 10]., This work was supported by the RD06/0020/0035 and RD12/0036/0048 grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, (Madrid, Spain and FONDOS FEDER); CB16/12/00400 and CB16/12/00233 grants, CIBERONC, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, (Madrid, Spain and FONDOS FEDER); the FIS PI06/0824-FEDER, PS09/02430-FEDER, PI12/00905-FEDER, DTS15/00119-FEDER, and PI17/00399-FEDER grants, from the Fondo de Investigación Sanitaria of Instituto de Salud Carlos III; the GRS206/A/08 grant (Ayuda al Grupo GR37 de Excelencia, SAN/1778/2009) from the Gerencia Regional de Salud (Consejería de Educación and Consejería de Sanidad of Castilla y León, Valladolid, Spain). MLG is supported by grant PTA2014-09963-I from the Instituto de Salud Carlos III and AR-C is supported by grant CB16/12/00400, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad.

Published
2018
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2. Risk of Cause-Specific Death in Individuals With Diabetes: A Competing Risks Analysis

Author

Baena-Díez, Jose Miguel, Peñafiel, Judit, Subirana, Isaac, Ramos, Rafel, Elosua, Roberto, Marín-Ibañez, Alejandro, Guembe, María Jesús, Rigo, Fernando, Tormo-Díaz, María José, Moreno-Iribas, Conchi, Cabré, Joan Josep, Segura, Antonio, García-Lareo, Manel, Gómez de la Cámara, Agustín, Lapetra, José, Quesada, Miquel, Marrugat, Jaume, Medrano, Maria José, Berjón, Jesús, Frontera, Guiem, Gavrila, Diana, Barricarte, Aurelio, Basora, Josep, García, Jose María, Pavone, Natalia C, Lora-Pablos, David, Mayoral, Eduardo, Franch, Josep, Mata, Manel, Castell, Conxa, Frances, Albert, Grau, María, FRESCO Investigators, [Miguel Baena-Diez, Jose] Hosp del Mar, Med Res Inst, REGICOR Study Grp Cardiovasc Epidemiol & Genet, Barcelona, Spain, [Penafiel, Judit] Hosp del Mar, Med Res Inst, REGICOR Study Grp Cardiovasc Epidemiol & Genet, Barcelona, Spain, [Subirana, Isaac] Hosp del Mar, Med Res Inst, REGICOR Study Grp Cardiovasc Epidemiol & Genet, Barcelona, Spain, [Elosua, Roberto] Hosp del Mar, Med Res Inst, REGICOR Study Grp Cardiovasc Epidemiol & Genet, Barcelona, Spain, [Marrugat, Jaume] Hosp del Mar, Med Res Inst, REGICOR Study Grp Cardiovasc Epidemiol & Genet, Barcelona, Spain, [Grau, Maria] Hosp del Mar, Med Res Inst, REGICOR Study Grp Cardiovasc Epidemiol & Genet, Barcelona, Spain, [Miguel Baena-Diez, Jose] Catalan Inst Hlth, Primary Care Ctr La Marina, Barcelona, Spain, [Garcia-Lareo, Manel] Catalan Inst Hlth, Primary Care Ctr La Marina, Barcelona, Spain, [Pavone, Natalia C.] Catalan Inst Hlth, Primary Care Ctr La Marina, Barcelona, Spain, [Miguel Baena-Diez, Jose] Catalan Inst Hlth, Primary Hlth Care Res Inst Jordi Gol, Barcelona, Spain, [Garcia-Lareo, Manel] Catalan Inst Hlth, Primary Hlth Care Res Inst Jordi Gol, Barcelona, Spain, [Pavone, Natalia C.] Catalan Inst Hlth, Primary Hlth Care Res Inst Jordi Gol, Barcelona, Spain, [Miguel Baena-Diez, Jose] Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Subirana, Isaac] Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Gomez de la Carnara, Agustin] Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Gavrila, Diana] Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Barricarte, Aurelio] Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Lora-Pablos, David] Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Ramos, Rafel] Catalan Inst Hlth, Family Med Res Unit, Girona, Spain, [Jose Tormo-Diaz, Maria] Catalan Inst Hlth, Family Med Res Unit, Girona, Spain, [Quesada, Miguel] Catalan Inst Hlth, Family Med Res Unit, Girona, Spain, [Ramos, Rafel] Catalan Inst Hlth, Primary Hlth Care Res Unit, Inst Jordi Gol, Girona, Spain, [Jose Tormo-Diaz, Maria] Catalan Inst Hlth, Primary Hlth Care Res Unit, Inst Jordi Gol, Girona, Spain, [Quesada, Miguel] Catalan Inst Hlth, Primary Hlth Care Res Unit, Inst Jordi Gol, Girona, Spain, [Ramos, Rafel] Univ Girona, Girona, Spain, [Marin-Ibanez, Alejandro] San Jose Norte Hlth Ctr, Zaragoza, Spain, [Jesus Guembe, Maria] Navarra Govt, Dept Hlth, Vasc Risk Navarra Res Grp, Pamplona, Spain, [Berjon, Jesus] Navarra Govt, Dept Hlth, Vasc Risk Navarra Res Grp, Pamplona, Spain, [Jesus Guembe, Maria] Navarra Govt, Dept Hlth, Knowledge Planning Evaluat & Management, Navarra, Spain, [Rigo, Fernando] Cardiovasc Grp Balear Isl, Palma De Mallorca, Spain, [Frontera, Guiem] Cardiovasc Grp Balear Isl, Palma De Mallorca, Spain, [Jose Tormo-Diaz, Maria] Murcian Hlth Dept, Murcia, Spain, [Jose Tormo-Diaz, Maria] Univ Murcia, Murcia, Spain, [Jose Tormo-Diaz, Maria] Murcian Inst Biomed Res, Murcia, Spain, [Moreno-Iribas, Conchi] Navarre Publ Hlth Inst, Pamplona, Spain, [Barricarte, Aurelio] Navarre Publ Hlth Inst, Pamplona, Spain, [Moreno-Iribas, Conchi] Res Network Hlth Serv Chron Dis, Pamplona, Spain, [Moreno-Iribas, Conchi] Navarra Hlth Res Inst, Pamplona, Spain, [Berjon, Jesus] Navarra Hlth Res Inst, Pamplona, Spain, [Barricarte, Aurelio] Navarra Hlth Res Inst, Pamplona, Spain, [Josep Cabre, Joan] Catalan Inst Hlth, Primary Care Ctr Sant Pere Ctr, Reus, Spain, [Josep Cabre, Joan] Catalan Inst Hlth, Primary Hlth Care Res Unit, Inst Jordi Gol, Reus, Spain, [Segura, Antonio] Castille La Mancha Government, Dept Hlth & Social Affairs, Hlth Sci Inst, Talavera De La Reina, Spain, [Maria Garcia, Jose] Castille La Mancha Government, Dept Hlth & Social Affairs, Hlth Sci Inst, Talavera De La Reina, Spain, [Gomez de la Carnara, Agustin] Hosp 12 Octubre Res Inst, Clin Res Dept, Madrid, Spain, [Lora-Pablos, David] Hosp 12 Octubre Res Inst, Clin Res Dept, Madrid, Spain, [Lapetra, Jose] Consortium Biomed Res Obes & Nutr, Madrid, Spain, [Mayora, Eduardo] Consortium Biomed Res Obes & Nutr, Madrid, Spain, [Lapetra, Jose] Primary Care Ctr San Pablo, Dept Family Med, Primary Care Div, Seville, Spain, [Jose Medrano, Maria] Carlos III Hlth Inst, Madrid, Spain, [Gavrila, Diana] Murcia Govt, Hlth & Consumers Dept, Murcia, Spain, [Basora, Josep] Catalan Inst Hlth, Primary Hlth Care Res Unit, Inst Jordi Gol, Reus, Spain, [Mayora, Eduardo] Andalusia Hlth Serv, Diabet Strategy, Seville, Spain, [Franch, Josep] Catalan Inst Hlth, Primary Care Ctr Raval Sud, Barcelona, Spain, [Franch, Josep] Catalan Inst Hlth, Primary Hlth Care Res Unit, Inst Jordi Gol, Barcelona, Spain, [Franch, Josep] Consortium Biomed Res Diabet & Associated Metab D, Madrid, Spain, [Mata, Manel] Primary Care Ctr La Mina, Barcelona, Spain, [Mata, Manel] Catalan Inst Hlth, Inst Jordi Gol, Primary Hlth Care Res Unit, Barcelona, Spain, [Castell, Conxa] Govt Catalonia, Publ Hlth Agcy, Barcelona, Spain, [Frances, Albert] Hosp del Mar, Dept Urol, Barcelona, Spain, [Grau, Maria] Univ Barcelona, Barcelona, Spain, MARATO TV3, Institute de Salud Carlos III-Fondo Europeo de Desarrollo Regional-European Regions Development Funds, Agency for Management of University and Research Grants, Consortium for Biomedical Research in Epidemiology and Public Health, Consortium for Biomedical Research in Obesity and Nutrition, and Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional-European Regions Development Fund FEDER

Subjects
Blood Glucose, Male, Complications, Endocrinology, Diabetes and Metabolism, Disease, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, Risk Factors, Cause of Death, Neoplasms, Cause of death, education.field_of_study, Diabetis, Hazard ratio, Diabetes, Metaanalysis, Middle Aged, Cardiovascular Diseases, Female, Risk assessment, Cohort study, Adult, medicine.medical_specialty, Coronary-heart-disease, Population, 030209 endocrinology & metabolism, Sistema cardiovascular -- Malalties -- Mortalitat, Risk Assessment, Càncer -- Mortalitat, 03 medical and health sciences, Life Expectancy, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Mortality, education, Aged, Advanced and Specialized Nursing, business.industry, Mellitus, Hazards, All-cause, Cardiovascular risk, medicine.disease, Myocardial-infarction, Glucose, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Multivariate Analysis, Life expectancy, business, Follow-Up Studies
Abstract

OBJECTIVE: Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death. RESEARCH DESIGN AND METHODS: We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths. RESULTS: We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes. CONCLUSIONS: Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes. This work was supported by MARATO TV3 (081630), Instituto de Salud Carlos III–Fondo Europeo de Desarrollo Regional–European Regions Development Funds (Red de Investigación Cardiovascular RD12/0042 [Programa HERACLES], Red RedIAPP RD12/0005, RD06/0018, PI081327, and PI1101801), Agency for Management of University and Research Grants (2014 SGR 240), Consortium for Biomedical Research in Epidemiology and Public Health, and Consortium for Biomedical Research in Obesity and Nutrition. M.G. was supported by the Instituto de Salud Carlos III– Fondo Europeo de Desarrollo Regional–European Regions Development Fund FEDER (FIS CP12/ 03287).

Published
2016

3. GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Author

Igor Rudan, Daniel I. Chasman, Helena Schmidt, Stefan Herms, Sharon L.R. Kardia, Oliver Stegle, Alison Pattie, Jenna Price, Gerardo Heiss, Karen A. Mather, L. J. Launer, Johan G. Eriksson, Christopher Oldmeadow, Ian Ford, Saira Saeed Mirza, Alan F. Wright, Ozren Polasek, Joshua M. Shulman, Maria K. Jonsdottir, André G. Uitterlinden, Rodney J. Scott, Kurt Lohman, Anita L. DeStefano, Peter W. Schofield, Perminder S. Sachdev, Stefania Bandinelli, Johan Wouter Jukema, John M. Starr, Rudolf S N Fehrmann, Y. C. Hsieh, William M. Meeks, Paul M. Ridker, R.G.J. Westendorp, Le Yu, J. C. van Swieten, Vilmundur Gudnason, Myriam Fornage, Melissa Garcia, Carla A. Ibrahim-Verbaas, James F. Wilson, Jean-Charles Lambert, Qiong Yang, Laura H. Coker, Stella Trompet, Lina Zgaga, Jennifer A. Smith, David J. Llewellyn, Nicole A. Kochan, Ben A. Oostra, Katja Petrovic, Peter Hoffmann, Qi Sun, James T. Becker, Najaf Amin, Vincent Chouraki, Brendan M. Buckley, D C Liewald, Jun Ding, Christiane Wolf, P. L. DeJager, Reinhold Schmidt, Chloe Fawns-Ritchie, Stéphanie Debette, Jing Wang, J. C. Bis, Nicola J. Armstrong, David J. Stott, Albert Hofman, Nazanin Karbalai, G. Eiriksdottir, Luke C. Pilling, D. S. Knopman, Maaike Schuur, Alexa S. Beiser, Annette L. Fitzpatrick, David A. Bennett, Aarno Palotie, Lude Franke, Sven Cichon, Mirna Kirin, Markus M. Nöthen, Thomas H. Mosley, Lynda M. Rose, Alan J. Gow, Caroline Hayward, Lori B. Chibnik, Ian J. Deary, Albert V. Smith, Jan Bressler, T.B. Harris, Stephen T. Turner, David J. Porteous, C M van Duijn, M. A. Ikram, Elizabeth G. Holliday, Mike A. Nalls, Luigi Ferrucci, Sudha Seshadri, Francine Grodstein, Marlene C. W. Stewart, Philip A. Wolf, Alexander Teumer, P.E. Slagboom, Jerome I. Rotter, Blair H. Smith, Juha Karjalainen, Susan M. Resnick, A.J.M. de Craen, Toshiko Tanaka, Alan D. Penman, Hans-Jörgen Grabe, Gary Davies, Oscar L. Lopez, Yongmei Liu, Kristine Yaffe, Veronique Vitart, Stela McLachlan, Katri Räikkönen, Rebecca F. Gottesman, Rhoda Au, Lynne J. Hocking, Carsten Oliver Schmidt, John Attia, Bruce M. Psaty, Wei Zhao, Jari Lahti, Epidemiology, Neurology, Clinical Genetics, Internal Medicine, [ 1 ] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands [ 2 ] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands [ 3 ] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA [ 4 ] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA [ 5 ] Univ Bordeaux, Epidemiol & Biostat, U897, INSERM, Bordeaux, France [ 6 ] Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France [ 7 ] Iceland Heart Assoc, Kopavogur, Iceland [ 8 ] Univ Iceland, Fac Med, Reykjavik, Iceland [ 9 ] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA [ 10 ] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland [ 11 ] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands [ 12 ] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands [ 13 ] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA [ 14 ] Max Planck Inst Psychiat, RG Stat Genet, Munich, Germany [ 15 ] Brigham & Womens Hosp, Div Neurol, Program Translat Neuropsychiat Gen, Boston, MA 02115 USA [ 16 ] Wake Forest Sch Med, Dept Epidemiol, Winston Salem, NC USA [ 17 ] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland [ 18 ] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland [ 19 ] Med Univ & Gen Hosp Graz, Dept Neurol, Graz, Austria [ 20 ] Univ Split, Dept Publ Hlth, Split, Croatia [ 21 ] Trintiy Coll Dublin, Dept Publ Hlth & Primary Care, Dublin, Ireland [ 22 ] Res Ctr Juelich, Inst Neurosci & Med INM1, Julich, Germany [ 23 ] Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland [ 24 ] Univ Bonn, Inst Human Genet, Life & Brain Res Ctr, Dept Genom, Bonn, Germany [ 25 ] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands [ 26 ] Univ Helsinki, Inst Behav Sci, Helsinki, Finland [ 27 ] Folkhalsan Res Ctr, Helsinki, Finland [ 28 ] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England [ 29 ] Univ Med Greifswald, Inst Community Med, Greifswald, Germany [ 30 ] Univ New S Wales, UNSW Med, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia [ 31 ] Univ Lille Nord France, Inst Pasteur Lille, U1167, INSERM, Lille, France [ 32 ] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA [ 33 ] Harvard Univ, Sch Med, Boston, MA USA [ 34 ] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA [ 35 ] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA [ 36 ] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2300, Australia [ 37 ] Univ Newcastle, Fac Hlth, Newcastle, NSW 2300, Australia [ 38 ] Univ Dundee, Med Res Inst, Dundee, Scotland [ 39 ] NHLBI, Framingham Heart Study, Framingham, MA USA [ 40 ] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA [ 41 ] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands [ 42 ] Netherlands Consortium Hlth Ageing, Leiden, Netherlands [ 43 ] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA [ 44 ] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland [ 45 ] Wake Forest Sch Med, Div Publ Hlth Sci & Neurol, Winston Salem, NC USA [ 46 ] Max Planck Inst Intelligent Syst, Max Planck Inst Dev Biol, Tubingen, Germany [ 47 ] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA [ 48 ] Univ Med Greifswald, Interfaculty Inst Genet & Funct Genom, Greifswald, Germany [ 49 ] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland [ 50 ] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA [ 51 ] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA [ 52 ] Landspitali Hosp, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital [ 53 ] NIA, Lab Neurogenet, Bethesda, MD 20892 USA [ 54 ] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA [ 55 ] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA [ 56 ] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA [ 57 ] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA [ 58 ] San Francisco VA Med Ctr, San Francisco, CA USA [ 59 ] Mayo Clin, Dept Neurol, Rochester, MN USA [ 60 ] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA [ 61 ] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA [ 62 ] Univ Newcastle, Fac Hlth, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia [ 63 ] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA [ 64 ] Univ Glasgow, Dept Cardiovasc & Med Sci, Glasgow, Lanark, Scotland [ 65 ] Alzheimer Scotland Res Ctr, Edinburgh, Midlothian, Scotland [ 66 ] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland [ 67 ] Garvan Inst Med Res, Canc Res Program, Sydney, NSW, Australia [ 68 ] Univ New S Wales, Sch Math & Stat, Sydney, NSW, Australia [ 69 ] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW, Australia [ 70 ] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA [ 71 ] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Dept Mol & Human Genet, Houston, TX 77030 USA [ 72 ] Univ Exeter, Sch Med, Epidemiol & Publ Hlth Grp, Exeter, Devon, England [ 73 ] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia [ 74 ] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England [ 75 ] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland [ 76 ] Univ Helsinki, Dept Med Genet, Helsinki, Finland [ 77 ] Univ Cent Hosp, Helsinki, Finland [ 78 ] Taipei Med Univ, Sch Publ Hlth, Taipei, Taiwan [ 79 ] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland [ 80 ] Natl Inst Hlth & Welf, Helsinki, Finland [ 81 ] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland [ 82 ] Vasa Cent Hosp, Vaasa, Finland [ 83 ] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA [ 84 ] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA [ 85 ] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA [ 86 ] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA [ 87 ] Harbor UCLA Med Ctr, Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA [ 88 ] Harbor UCLA Med Ctr, Dept Pediat, Div Genet Outcomes, Torrance, CA 90509 USA [ 89 ] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany [ 90 ] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands [ 91 ] Leiden Acad Vital & Ageing, Leiden, Netherlands [ 92 ] Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland [ 93 ] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands [ 94 ] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA [ 95 ] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA [ 96 ] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA [ 97 ] HELIOS Hosp Stralsund, Univ Med Greifswald, Dept Psychiat & Psychotherapy, Stralsund, Germany [ 98 ] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy [ 99 ] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland [ 100 ] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA [ 101 ] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA [ 102 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA [ 103 ] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands [ 104 ] Univ Mississippi, Med Ctr, Dept Med & Neurol, Jackson, MS 39216 USA, Human genetics, Amsterdam Neuroscience - Neurodegeneration, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Stem Cell Aging Leukemia and Lymphoma (SALL)

Subjects
0301 basic medicine, Male, DISORDER, Trail Making Test, LOCI, Genome-wide association study, INTELLIGENCE, Neuropsychological Tests, Cohort Studies, Exon, Executive Function, 0302 clinical medicine, Cognition, SCHIZOPHRENIA, ONSET ALZHEIMERS-DISEASE, CADM2 protein, human, genetics [Cell Adhesion Molecules], gamma-Aminobutyric Acid, Genetics, Aged, 80 and over, PSC12, physiology [Cognition], COMMON VARIANTS, Genomics, Middle Aged, genetics [Genetic Variation], 3. Good health, physiology [Executive Function], Psychiatry and Mental health, genetics [European Continental Ancestry Group], Schizophrenia, Female, Psychology, EXPRESSION, genetics [White People], physiology [Cell Adhesion Molecules], Polymorphism, Single Nucleotide, White People, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Genetic variation, medicine, SNP, Humans, ddc:610, GENOME-WIDE ASSOCIATION, Molecular Biology, Gene, Genetic Association Studies, Aged, LINKAGE ANALYSIS, 9. Industry and infrastructure, Genetic Variation, medicine.disease, COGNITIVE FUNCTION, Introns, 030104 developmental biology, Cell Adhesion Molecules, 030217 neurology & neurosurgery, Stroop effect, Genome-Wide Association Study
Abstract

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed. National Foundation for Alzheimer's disease and related disorders Institut Pasteur de Lille Centre National de Genotypage Inserm FRC (fondation pour la recherche sur le cerveau) Rotary LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease) MEDIALZ Project - ERDF (European Regional Development Fund) 11001003 Conseil Regional Nord Pas de Calais Fondation pour la Recherche Medicale Caisse Nationale Maladie des Travailleurs Salaries Direction Generale de la Sante MGEN Institut de la Longevite Agence Francaise de Securite Sanitaire des Produits de Sante Aquitaine and Bourgogne Regional Councils Fondation de France joint French Ministry of Research/INSERM 'Cohortes et collections de donnees biologiques' program Eisai Wellcome Trust British Heart Foundation Chief Scientist Office of the Scottish Executive NIA N01-AG-12100 National Heart, Lung and Blood Institute Contracts HHSN268201100005C HHSN268201100006C HHSN268201100007C HHSN268201100008C HHSN268201100009C HHSN268201100010C HHSN268201100011C HHSN268201100012C R01HL70825 R01HL087641 R01HL59367 R01HL086694 National Human Genome Research Institute U01HG004402 NIH Roadmap for Medical Research Austrian Science Fond (FWF) P20545-P05 P13180 Intramural Research Program of the NIH, National Institute on Aging NHLBI HHSN268201200036C HHSN268200800007C N01HC55222 N01HC85079 N01HC85080 N01HC85081 N01HC85082 N01HC85083 N01HC850863 U01HL080295 R01HL087652 R01HL105756 R01HL103612 R01HL120393 National Institute of Neurological Disorders and Stroke (NINDS) National Institute on Aging (NIA) R01AG023629 R01AG15928 R01AG20098 R01AG027058 National Center for Advancing Translational Sciences CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) DK063491 Medical Research Council (UK) European Commission Framework 6 project EUROSPAN LSHG-CT-2006-018947 Republic of Croatia Ministry of Science, Education and Sports 108-1080315-0302 Netherlands Organization for Scientific Research (NWO) Internationale Stichting Alzheimer Onderzoek (ISAO) Hersenstichting Nederland (HSN) Centre for Medical Systems Biology (CMSB) in the framework of the Netherlands Genomics Initiative (NGI) Russian Foundation for Basic Research (RFBR) National Heart, Lung and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc N02-HL-6-4278 U01 HL096917 R01 HL093029 Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine Boston Medical Center National Institute of Neurological Disorders and Stroke NS17950 National Institute of Aging U01 AG049505 AG033193 AG008122 AG16495 Agence National de la Recherche Leducq Foundation National Heart, Lung and Blood Institute HL054464 HL054457 HL054481 HL071917 HL87660 HL043851 HL080467 National Institute of Neurological Disorders and Stroke of the National Institutes of Health NS041558 Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 Scottish Funding Council HR03006 Academy of Finland Finnish Diabetes Research Society Folkhalsan Research Foundation Novo Nordisk Foundation Finska Lakaresallskapet Signe and Ane Gyllenberg Foundation University of Helsinki Ministry of Education Ahokas Foundation Emil Aaltonen Foundation Juho Vainio Foundation Wellcome Trust WT089062 University of Newcastle's Strategic Initiative Fund Vincent Fairfax Family Foundation Hunter Medical Research Institute Italian Ministry of Health ICS 110.1RS97.71 US National Institute on Aging N01[AG]916413 N01[AG]821336 263 MD 9164 13 263 MD 821336 Intramural Research Program, National Institute on Aging, National Institutes of Health BBSRC Royal Society Chief Scientist Office of the Scottish Government Research Into Ageing UK Biotechnology and Biological Sciences Research Council (BBSRC) Engineering and Physical Sciences Research Council (EPSRC) Economic and Social Research Council (ESRC) MRC NHMRC 401184 Australian National Health & Medical Research Council 350833 568969 Capacity Building Grant 568940 NHMRC Project 525453 National Institutes of Health CA87969 CA49449 HL34594 U01HG004399 DK058845 CA65725 CA67262 CA50385 5UO1CA098233 EY09611 EY015473 HG004728 HL35464 CA55075 CA134958 DK070756 MRC Human Genetics Unit Arthritis Research UK European Union LSHG-CT-2006-018947 Bristol-Myers Squibb Netherlands Heart Foundation 2001 D 032 European commission 223004 Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) 050-060-810 Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project 050-060-810 Erasmus Medical Center Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission 49 (DG XII) Municipality of Rotterdam ZonMW Veni Grant 916.13.054 NIA Grants P30AG10161 R01AG15819 R01AG17917 R01AG30146 K08AG34290 K25AG41906 Federal Ministry of Education and Research 01ZZ9603 01ZZ0103 01ZZ0403 Ministry of Cultural Affairs Social Ministry of the Federal State of Mecklenburg-West Pomerania National Cancer Institute CA047988 Donald W Reynolds Foundation Fondation Leducq Amgen info:eu-repo/grantAgreement/EC/FP7/223004

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2016
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4. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

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Tazeen H. Jafar, Lars Lind, Peter Almgren, Wendy Winckler, Eitaro Nakashima, Young Min Cho, Annette Peters, Rona J. Strawbridge, Ananda R. Wickremasinghe, Katharine R. Owen, Lee-Ming Chuang, Tien-Jyun Chang, Graeme I. Bell, James B. Meigs, Bill Musk, Timo A. Lakka, Elin Grundberg, Wei Lu, Sarah Edkins, George Dedoussis, Weiping Jia, Danish Saleheen, Suthesh Sivapalaratnam, Maria Samuel, Tien Yin Wong, Lu Qi, Pierre Fontanillas, Momoko Horikoshi, Jirong Long, Abdul Basit, Anubha Mahajan, Andrew T. Hattersley, Markus M. Nöthen, Denis Rybin, Inger Njølstad, S. Krithika, Miguel Cruz, Delilah Zabaneh, Leena Peltonen, Jasmina Kravic, Sangsoo Kim, David Couper, Lori L. Bonnycastle, Heather M. Stringham, Yi-Cheng Chang, Paul Elliott, Eric J.G. Sijbrands, Nita G. Forouhi, Alena Stančáková, Ghazala Mirza, Robert W. Lawrence, Ruth J. F. Loos, Norman Klopp, Shiro Maeda, Martina Müller-Nurasyid, Jer-Yuarn Wu, Jianjun Liu, Kee Seng Chia, Elodie Eury, Loukianos S. Rallidis, Timothy M. Frayling, Ken Yamamoto, David Altshuler, Gunnar Sigurosson, Harald Grallert, Jackie F. Price, Barbara Thorand, Jouko Saramies, Malene M. Kristensen, Sonali Pechlivanis, Inês Barroso, Jong-Young Lee, Melissa Parkin, Josée Dupuis, Stéphane Lobbens, Jesús Kumate, Elena Tremoli, Sudhir Kowlessur, Xueling Sim, Norihiro Kato, Philippe Froguel, Kathleen Stirrups, Eero Lindholm, Alex S. F. Doney, Andres Metspalu, Yu-Tang Gao, Roman Wennauer, Xiao-Ou Shu, Marilyn C. Cornelis, Veikko Salomaa, Nanette R. Lee, Johanna Kuusisto, Caroline S. Fox, Man Li, James Scott, Wing-Yee So, Andrew R. Wood, Inga Prokopenko, Oddgeir L. Holmen, Tin Aung, Ryoichi Takayanagi, Chen Suo, Hara Kazuo, Carl G. P. Platou, Ann M. Kelly, Teresa Ferreira, Karl-Heinz Jöckel, Wei-Yen Lim, James F. Wilson, Tom Forsén, Qi Sun, Valur Emilsson, Gonçalo R. Abecasis, Fan Zhang, Timo Saaristo, Harry Campbell, Ying Wu, Mark Seielstad, Wei Zheng, Han Chen, Stavroula Kanoni, Yuqian Bao, Jose C. Florez, Wan Ting Tay, Ronald C. WMa, Gerald Steinbach, Min Jin Go, Rong Zhang, Junbin Liang, Vasiliki Lagou, Leif Groop, Emil Rehnberg, Nabi Shah, Weihua Zhang, Yun Li, Bengt Sennblad, Olle Melander, Nancy L. Pedersen, Muhammed Islam, Jaakko Tuomilehto, Young Jin Kim, Richard N. Bergman, Juliana C.N. Chan, Eleftheria Zeggini, Andrew D. Johnson, Kees Hovingh, Joban Sehmi, Rainer Rauramaa, Satu Männistö, Reedik Mägi, Samuel Liju, Mingyu Yang, Ayellet V. Segrè, Noël P. Burtt, Mozhgan Dorkhan, Beverley Balkau, Neelam Hassanali, Hyun Min Kang, Fabrizio Veglia, Eeva Korpi-Hyövälti, Loic Yengo, Elizabeth J. Rossin, Angela Silveira, Maggie C.Y. Ng, Yuan-Tsong Chen, Anders Hamsten, David R. Matthews, Mark J. Caulfield, Emmi Tikkanen, Tanya M. Teslovich, John R. B. Perry, Karen L. Mohlke, Sarah E. Hunt, Soo Heon Kwak, Jorge Escobedo, Christopher J. Groves, Ulf de Faire, Jeremy B M Jowett, Gudmar Thorleifsson, Michael Roden, Evelin Mihailov, Viswanathan Mohan, Craig L. Hanis, Thomas WMühleisen, Congrong Wang, Sonia Shah, Kyle J. Gaulton, Jaspal S. Kooner, Jiro Nakamura, Mustafa Atalay, Linda S. Adair, S Wiltshire, Tõnu Esko, Anna Jonsson, Antigone S. Dimas, Karin Leander, Li Ching Chang, George B. Grant, Bo Isomaa, Anne U. Jackson, Claudia Langenberg, Kristian Hveem, Yoon Shin Cho, Astradur B. Hreidarsson, Xu Wang, Keizo Ohnaka, Alexandra C. Nica, Simon D. Rees, Pau Navarro, Sekar Kathiresan, Rob M. van Dam, Zafar I. Hydrie, Bok Ghee Han, Francis S. Collins, Fuu Jen Tsai, Unnur Thorsteinsdottir, Ross M. Fraser, Caroline Hayward, Cornelia M. van Duijn, Samuli Ripatti, Mieke D. Trip, Hyung Lae Kim, Rafn Benediktsson, Candace Guiducci, Bruna Gigante, Kyong Soo Park, Wen Hong L. Kao, Tom Wilsgaard, Leena Kinnunen, John Danesh, Alan James, Alan R. Shuldiner, Mitsuhiro Yokota, Jen Mai Lee, Kari Stefansson, Erik Ingelsson, Colin N. A. Palmer, David J. Hunter, Paul Zimmet, Manickam Chidambaram, Sirkka Keinänen-Kiukaanniemi, Laura J. Scott, Susanne Moebus, Benjamin F. Voight, Wolfgang Rathmann, Hassan Khan, Thomas Illig, Prasad Katulanda, Christian Gieger, Andrew D. Morris, Yik Ying Teo, Andrew P. Morris, Venkatesan Radha, N. William Rayner, Johan G. Eriksson, Christian Dina, Igor Rudan, Sailaja Vedantam, Cheng Hu, James S. Pankow, Ann-Christine Syvänen, Karl Gertow, Valeriya Lyssenko, Guillaume Charpentier, Albert Hofman, Chiea Chuen Khor, Joseph Trakalo, Peter Kraft, Takashi Kadowaki, Qiuyin Cai, John C. Chambers, André G. Uitterlinden, Simon C. Potter, Nicholas J. Wareham, Soumya Raychaudhuri, Jian'an Luan, Tiinamaija Tuomi, Anthony H. Barnett, Juha Saltevo, Robert A. Scott, Valgerdur Steinthorsdottir, Peng Keat Ng, Mark I. McCarthy, Åsa K. Hedman, Kerrin S. Small, Julia Meyer, Frank B. Hu, Cecilia M. Lindgren, Jennifer E. Below, Nancy J. Cox, Jennie Hui, Andrew Crenshaw, Latonya F. Been, Nam H. Cho, Janani Pinidiyapathirage, A. Samad Shera, Bernhard OBoehm, Jason Carey, Augustine Kong, Twee Hee Ong, Philippe M. Frossard, Donald W. Bowden, Toshimasa Yamauchi, Steve E. Humphries, Cordelia Langford, Xinzhong Li, Hiroshi Ikegami, Stéphane Cauchi, Ching-Ti Liu, Michael Boehnke, Peter M. Nilsson, Debashish Das, John Beilby, Robin Young, Christian Herder, Asif Rasheed, Neil Robertson, Raimund Erbel, Fumihiko Takeuchi, Markku Laakso, Esteban J. Parra, Panos Deloukas, Eric Boerwinkle, Adan Valladares-Salgado, Chien-Hsiun Chen, Kay-Tee Khaw, Damiano Baldassarre, Ashok Kumar, E. Shyong Tai, Peter S. 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Hlth Trust, Levanger Hosp, Dept Internal Med, Levanger, Norway [ 178 ] Univ Gen Hosp Attikon, Athens, Greece [ 179 ] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany [ 180 ] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland [ 181 ] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA [ 182 ] Partners Ctr Personalized Genom Med, Boston, MA USA [ 183 ] Univ Dusseldorf, Dept Endocrinol & Diabetol, Dusseldorf, Germany [ 184 ] Univ Dusseldorf, Dept Metab Dis, Dusseldorf, Germany [ 185 ] Harvard Univ, Hlth Sci & Technol MD Program, Boston, MA 02115 USA [ 186 ] MIT, Boston, MA USA [ 187 ] Harvard Univ, Harvard Biol & Biomed Sci Program, Boston, MA 02115 USA [ 188 ] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA [ 189 ] Finnish Diabet Assoc, Tampere, Finland [ 190 ] Pirkanmaa Hosp Dist, Tampere, Finland [ 191 ] Cent Finland Cent Hosp, Dept Med, Jyvaskyla, Finland [ 192 ] South Karelia Cent Hosp, Lappeenranta, Finland [ 193 ] UCL, Dept Genet Evolut & Environm, Genet Inst, London, England [ 194 ] Diabet Assoc Pakistan, Karachi, Pakistan [ 195 ] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA [ 196 ] Baltimore Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA [ 197 ] Univ Maryland, Sch Med, Program Personalised & Genom Med, Baltimore, MD 21201 USA [ 198 ] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands [ 199 ] Univ Ulm, Dept Clin Chem, D-89069 Ulm, Germany [ 200 ] Univ Ulm, Cent Lab, D-89069 Ulm, Germany [ 201 ] Uppsala Univ, Dept Med Sci, Uppsala, Sweden [ 202 ] Kyushu Univ, Grad Sch Med Sci, Dept Internal Med & Bioregulatory Sci, Higashi Ku, Fukuoka 812, Japan [ 203 ] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland [ 204 ] Hosp Univ LaPaz IdiPAZ, Inst Invest Sanitaria, Madrid, Spain [ 205 ] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria [ 206 ] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia [ 207 ] IMSS, Ctr Med Nacl Siglo 21, Hosp Especialidades, Unidad Invest Med Bioquim, Mexico City, DF, Mexico [ 208 ] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA [ 209 ] Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic, Australia [ 210 ] Kyushu Univ, Med Inst Bioregulat, Res Ctr Genet Informat, Div Genome Anal,Higashi Ku, Fukuoka 812, Japan [ 211 ] Univ Lille 1, Math Lab, CNRS UMR 8524, MODAL Team,INRIA Lille Nord Europe, F-59655 Villeneuve Dascq, France [ 212 ] Aichi Gakuin Univ, Sch Dent, Dept Genome Sci, Nagoya, Aichi 464, Japan [ 213 ] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA [ 214 ] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA [ 215 ] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA [ 216 ] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA [ 217 ] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA [ 218 ] Hallym Univ, Dept Biomed Sci, Chunchon, Gangwon Do, South Korea [ 219 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA [ 220 ] Imperial Coll Healthcare NHS Trust, London, England [ 221 ] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA [ 222 ] Blood Syst Res Inst, San Francisco, CA USA [ 223 ] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore [ 224 ] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore [ 225 ] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore [ 226 ] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore [ 227 ] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England, Obstetrics & Gynecology, Radiology & Nuclear Medicine, Surgery, Epidemiology, Dermatology, Internal Medicine, Medical Microbiology & Infectious Diseases, Medical Research Council (MRC), National Institute for Health Research, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, and Cardiology

Subjects
CHROMATIN, endocrine system diseases, South Asian Type 2 Diabetes (SAT2D) Consortium, SCALE ASSOCIATION ANALYSIS, Medizin, LOCI, Genome-wide association study, VARIANTS, 0302 clinical medicine, Risk Factors, IMPUTATION, Glucose homeostasis, 11 Medical and Health Sciences, Genetics & Heredity, Genetics, 0303 health sciences, IDENTIFY, Hispanic or Latino, 3. Good health, MAP, POPULATIONS, Medical genetics, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, Hispanic Americans, Life Sciences & Biomedicine, Asian Continental Ancestry Group, medicine.medical_specialty, European Continental Ancestry Group, TRANSETHNIC METAANALYSIS, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, Sykursýki, 03 medical and health sciences, Asian People, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, Allele, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, Alleles, 030304 developmental biology, Genetic association, Science & Technology, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, 06 Biological Sciences, Arfgengi, Genetic architecture, INDIVIDUALS, Diabetes Mellitus, Type 2, Case-Control Studies, GLUCOSE-HOMEOSTASIS, ASSOCIATION ANALYSES, Imputation (genetics), Developmental Biology, Genome-Wide Association Study
Abstract

To access publisher's full text version of this article click on the hyperlink at the bottom of the page To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry. Canadian Institutes of Health Research Medical Research Council UK G0601261 Mexico Convocatoria SSA/IMMS/ISSSTE-CONACYT 2012-2 clave 150352 IMSS R-2011-785-018 CONACYT Salud-2007-C01-71068 US National Institutes of Health DK062370 HG000376 DK085584 DK085545 DK073541 DK085501 Wellcome Trust WT098017 WT090532 WT090367 WT098381 WT081682 WT085475 info:eu-repo/grantAgreement/EC/FP7/201413

Published
2014
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5. HLA class II sequence variants influence tuberculosis risk in populations of European ancestry

Author

Ari Karason, Jeffrey C. Barrett, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Adalbjorg Jonasdottir, Kai Blöndal, Olafur Th Magnusson, Aslaug Jonasdottir, Hafdis T. Helgadottir, Larus J. Gudmundsson, Helgi Kristjansson, Yang Luo, Kari Stefansson, Gardar Sveinbjornsson, Gisli Masson, Mar Kristjansson, Arnaldur Gylfason, Augustine Kong, Ljiljana Bulat Kardum, Sigurjon A. Gudjonsson, Ingileif Jonsdottir, Arthur Löve, Jelena Knežević, Magnus Gottfredsson, Bjarni V. Halldorsson, Thorsteinn Blondal, Zlatko Dembic, Sergey Nejentsev, Karl G. Kristinsson, Patrick Sulem, and [ 1 ] Amgen Inc, deCODE Genet, Reykjavik, Iceland [ 2 ] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland [ 3 ] Reykjavik Univ, Sch Sci & Engn, Reykjavik, Iceland [ 4 ] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland [ 5 ] Natl Univ Hosp Iceland, Dept Clin Microbiol, Landspitali, Reykjavik, Iceland [ 6 ] Natl Univ Hosp Iceland, Dept Infect Dis, Landspitali, Reykjavik, Iceland [ 7 ] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England [ 8 ] Primary Hlth Care Capital Area, Div Communicable Dis Prevent & Control, Reykjavik, Iceland [ 9 ] Univ Rijeka, Dept Pulmonol, Clin Internal Med, Clin Hosp Ctr, Rijeka, Croatia [ 10 ] Univ Oslo, Fac Dent, Dept Oral Biol, Mol Genet Lab, Oslo, Norway [ 11 ] Rudjer Boskovic Inst, Div Mol Med, Zagreb, Croatia [ 12 ] Natl Univ Hosp Iceland, Landspitali, Dept Virol, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital [ 13 ] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England [ 14 ] Natl Univ Hosp Iceland, Landspitali, Dept Immunol, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital

Subjects
0301 basic medicine, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, T-Lymphocytes, Iceland, Genome-wide association study, TMD12, 0302 clinical medicine, Gene Frequency, Risk Factors, Genetics, variants, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, Berklar, 3. Good health, Europe, BAC12, tuberculosis, 030220 oncology & carcinogenesis, NAF12, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, Tuberculosis, Human leukocyte antigen, Biology, Article, HLA-DQ alpha-Chains, White People, 03 medical and health sciences, Antigen, medicine, Humans, Genetic Predisposition to Disease, HLA class II, Allele, Tuberculosis, Pulmonary, Allele frequency, Alleles, PAD12, Genome, Human, HLA-DR Antigens/genetics, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Genetic Variation, Mycobacterium tuberculosis, Odds ratio, Arfgengi, medicine.disease, Virology, Tuberculosis, Pulmonary/genetics, Minor allele frequency, 030104 developmental biology, Genome-Wide Association Study, HLA-DRB1 Chains
Abstract

To access publisher's full text version of this article click on the hyperlink at the bottom of the page Mycobacterium tuberculosis infections cause 9 million new tuberculosis cases and 1.5 million deaths annually. To identify variants conferring risk of tuberculosis, we tested 28.3 million variants identified through whole-genome sequencing of 2,636 Icelanders for association with tuberculosis (8,162 cases and 277,643 controls), pulmonary tuberculosis (PTB) and M. tuberculosis infection. We found association of three variants in the region harboring genes encoding the class II human leukocyte antigens (HLAs): rs557011[T] (minor allele frequency (MAF) = 40.2%), associated with M. tuberculosis infection (odds ratio (OR) = 1.14, P = 3.1 × 10(-13)) and PTB (OR = 1.25, P = 5.8 × 10(-12)), and rs9271378[G] (MAF = 32.5%), associated with PTB (OR = 0.78, P = 2.5 × 10(-12))-both located between HLA-DQA1 and HLA-DRB1-and a missense variant encoding p.Ala210Thr in HLA-DQA1 (MAF = 19.1%, rs9272785), associated with M. tuberculosis infection (P = 9.3 × 10(-9), OR = 1.14). We replicated association of these variants with PTB in samples of European ancestry from Russia and Croatia (P < 5.9 × 10(-4)). These findings show that the HLA class II region contributes to genetic risk of tuberculosis, possibly through reduced presentation of protective M. tuberculosis antigens to T cells. US National Institute of Allergy and Infectious Diseases HHSN266200400064C UK Wellcome Trust 088838/Z/09/Z 095198/Z/10/Z info:eu-repo/grantAgreement/EC/FP7/201483 European Research Council Starting 260477 Royal Society UF0763346 RG090638 Wellcome Trust Senior Research fellowship National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre

Published
2016

6. Population structure and geographical subdivision of the Leishmania major vector Phlebotomus papatasi as revealed by microsatellite variation

Author

Omar Hamarsheh, Gabriele Schönian, M. L. Das, Amer Al-Jawabreh, M. Hassan, Y. Hashiguchi, Ramesh C. Dhiman, Ahmad Amro, Ahmad Al-Lahem, Wolfgang Presber, J. Ghrab, N. Seridi, Samir S. Sawalha, Souad Guernaoui, Mohammad Reza Yaghoobi-Ershadi, Dept Biol Sci, Al-Quds University, Dept Parasitol, Charite, Inst Microbiol & Hyg, University of Tehran, Dept Med Entomol & Vector Control, Tehran University, Leishmaniasis Res Lab, Leishmania Res Unit, Jericho, Dept Primary Hlth Care, Minist Hlth, Dept Zool, University of Aleppo [Aleppo], Dept Microbiol, BP Koirala Inst Hlth Sci, Lab Ecol Anim Terrestre, Faculté des Sciences Semlalia, Genet Lab, USTHB, Fac Biol Sci, Natl Inst Malaria Res ICMR, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Natl Res Ctr, Res Inst Trop Med, and Kochi Univ, Kochi Med Sch

Subjects
sandflies, Genotype, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Population, Population Dynamics, Population genetics, India, microsatellites, 03 medical and health sciences, Middle East, 0302 clinical medicine, Nepal, Animals, Psychodidae, education, Phlebotomus papatasi, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Leishmania major, Genetics, 0303 health sciences, education.field_of_study, General Veterinary, biology, population structure, biology.organism_classification, Sandfly, Insect Vectors, F-statistics, Evolutionary biology, Insect Science, Phlebotomus, Genetic structure, Africa, Microsatellite, Biological dispersal, Parasitology
Abstract

International audience; Multi-locus microsatellite typing (MLMT) has been employed to infer the population structure of Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae) sandflies and assign individuals to populations. Phlebotomus papatasi sandflies were collected from 35 sites in 15 countries. A total of 188 P. papatasi individuals were typed using five microsatellite loci, resulting in 113 different genotypes. Unique microsatellite signatures were observed for some of the populations analysed. Comparable results were obtained when the data were analysed with Bayesian model and distance-based methods. Bayesian statistic-based analyses split the dataset into two distinct genetic clusters, A and B, with further substructuring within each. Population A consisted of five subpopulations representing large numbers of alleles that were correlated with the geographical origins of the sandflies. Cluster B comprised individuals collected in the Middle East and the northern Mediterranean area. The subpopulations B1 and B2 did not, however, show any further correlation to geographical origin. The genetic differentiation between subpopulations was supported by F statistics showing statistically significant (Bonferroni-corrected P < 0.005) values of 0.221 between B2 and B1 and 0.816 between A5 and A4. Identification of the genetic structure of P. papatasi populations is important for understanding the patterns of dispersal of this species and to developing strategies for sandfly control.

Published
2009
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