Author: "Carla A Ibrahim-Verbaas" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

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20 results on '"Carla A Ibrahim-Verbaas"'

1. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

Author: Valentina Escott-Price, Céline Bellenguez, Li-San Wang, Seung-Hoan Choi, Denise Harold, Lesley Jones, Peter Holmans, Amy Gerrish, Alexey Vedernikov, Alexander Richards, Anita L DeStefano, Jean-Charles Lambert, Carla A Ibrahim-Verbaas, Adam C Naj, Rebecca Sims, Gyungah Jun, Joshua C Bis, Gary W Beecham, Benjamin Grenier-Boley, Giancarlo Russo, Tricia A Thornton-Wells, Nicola Denning, Albert V Smith, Vincent Chouraki, Charlene Thomas, M Arfan Ikram, Diana Zelenika, Badri N Vardarajan, Yoichiro Kamatani, Chiao-Feng Lin, Helena Schmidt, Brian Kunkle, Melanie L Dunstan, Maria Vronskaya, United Kingdom Brain Expression Consortium, Andrew D Johnson, Agustin Ruiz, Marie-Thérèse Bihoreau, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Olivier Hanon, Annette L Fitzpatrick, Joseph D Buxbaum, Dominique Campion, Paul K Crane, Clinton Baldwin, Tim Becker, Vilmundur Gudnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Oscar L Lopez, Philip L De Jager, Vincent Deramecourt, Janet A Johnston, Denis Evans, Simon Lovestone, Luc Letenneur, Isabel Hernández, David C Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison M Goate, Nathalie Fiévet, Matthew J Huentelman, Michael Gill, Kristelle Brown, M Ilyas Kamboh, Lina Keller, Pascale Barberger-Gateau, Bernadette McGuinness, Eric B Larson, Amanda J Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George-Hyslop, Jordi Clarimon, Alberto Lleo, Anthony Bayer, Debby W Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petra Proitsi, John Collinge, Sandro Sorbi, Florentino Sanchez Garcia, Nick C Fox, John Hardy, Maria Candida Deniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Elio Scarpini, Ubaldo Bonuccelli, Michelangelo Mancuso, Gabriele Siciliano, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, Ana Frank-García, Francesco Panza, Vincenzo Solfrizzi, Paolo Caffarra, Benedetta Nacmias, William Perry, Manuel Mayhaus, Lars Lannfelt, Hakon Hakonarson, Sabrina Pichler, Minerva M Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Alvarez, Fanggeng Zou, Otto Valladares, Steven G Younkin, Eliecer Coto, Kara L Hamilton-Nelson, Wei Gu, Cristina Razquin, Pau Pastor, Ignacio Mateo, Michael J Owen, Kelley M Faber, Palmi V Jonsson, Onofre Combarros, Michael C O'Donovan, Laura B Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H Mosley, David A Bennett, Tamara B Harris, Laura Fratiglioni, Clive Holmes, Renee F A G de Bruijn, Peter Passmore, Thomas J Montine, Karolien Bettens, Jerome I Rotter, Alexis Brice, Kevin Morgan, Tatiana M Foroud, Walter A Kukull, Didier Hannequin, John F Powell, Michael A Nalls, Karen Ritchie, Kathryn L Lunetta, John S K Kauwe, Eric Boerwinkle, Matthias Riemenschneider, Mercè Boada, Mikko Hiltunen, Eden R Martin, Reinhold Schmidt, Dan Rujescu, Jean-François Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M Nöthen, Caroline Graff, Bruce M Psaty, Jonathan L Haines, Mark Lathrop, Margaret A Pericak-Vance, Lenore J Launer, Christine Van Broeckhoven, Lindsay A Farrer, Cornelia M van Duijn, Alfredo Ramirez, Sudha Seshadri, Gerard D Schellenberg, Philippe Amouyel, Julie Williams, and Cardiovascular Health Study (CHS)
Subjects: Medicine, Science
Abstract: BACKGROUND:Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. PRINCIPAL FINDINGS:In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. SIGNIFICANCE:The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Published: 2014
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2. Human prion diseases in the Netherlands (1998-2009): clinical, genetic and molecular aspects.

Author: Casper Jansen, Piero Parchi, Sabina Capellari, Carla A Ibrahim-Verbaas, Maaike Schuur, Rosaria Strammiello, Patrizia Corrado, Matthew T Bishop, Willem A van Gool, Marcel M Verbeek, Frank Baas, Wesley van Saane, Wim G M Spliet, Gerard H Jansen, Cornelia M van Duijn, and Annemieke J M Rozemuller
Subjects: Medicine, Science
Abstract: Prion diseases are rare and fatal neurodegenerative disorders that can be sporadic, inherited or acquired by infection. Based on a national surveillance program in the Netherlands we describe here the clinical, neuropathological, genetic and molecular characteristics of 162 patients with neuropathologically confirmed prion disease over a 12-year period (1998-2009). Since 1998, there has been a relatively stable mortality of Creutzfeldt-Jakob disease (CJD) in the Netherlands, ranging from 0.63 to 1.53 per million inhabitants per annum. Genetic analysis of the codon 129 methionine/valine (M/V) polymorphism in all patients with sporadic CJD (sCJD) showed a trend for under-representation of VV cases (7.0%), compared with sCJD cohorts in other Western countries, whereas the MV genotype was relatively over-represented (22,4%). Combined PrP(Sc) and histopathological typing identified all sCJD subtypes known to date, except for the VV1 subtype. In particular, a "pure" phenotype was demonstrated in 60.1% of patients, whereas a mixed phenotype was detected in 39.9% of all sCJD cases. The relative excess of MV cases was largely accounted for by a relatively high incidence of the MV 2K subtype. Genetic analysis of the prion protein gene (PRNP) was performed in 161 patients and showed a mutation in 9 of them (5.6%), including one FFI and four GSS cases. Iatrogenic CJD was a rare phenomenon (3.1%), mainly associated with dura mater grafts. Three patients were diagnosed with new variant CJD (1.9%) and one with variably protease-sensitive prionopathy (VPSPr). Post-mortem examination revealed an alternative diagnosis in 156 patients, most commonly Alzheimer's disease (21.2%) or vascular causes of dementia (19.9%). The mortality rates of sCJD in the Netherlands are similar to those in other European countries, whereas iatrogenic and genetic cases are relatively rare. The unusual incidence of the VV2 sCJD subtype compared to that reported to date in other Western countries deserves further investigation.
Published: 2012
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3. Genome-wide association study identifies risk variants for sporadic Creutzfeldt-Jakob disease in STX6 and GAL3ST1

Author: Anna Poleggi, John Collinge, Carla A. Ibrahim-Verbaas, Jean-Philippe Brandel, Emma Jones, Dimitriadis A, Anna Bartoletti-Stella, James Uphill, Christiane Stehmann, Mok Th, Gerard H. Jansen, Tracy Campbell, Zafar S, Holger Hummerich, van Duijn C, Jiri G. Safar, Ewa Golanska, Martinón-Torres F, Aili Golubjatnikov, Michael B. Coulthart, Zane Jaunmuktane, Beata Sikorska, Giuseppe Matullo, Miguel Calero, Jerome Whitfield, Sabina Capellari, Jean-Louis Laplanche, Kathleen Glisic, Gabor G. Kovacs, Richard Knight, Helen Speedy, Juan Ps, Olga Calero, Jean-Charles Lambert, Stéphane Haïk, Anna Ladogana, Akin Nihat, Stephanie A. Booth, Serena Aneli, Herbert Budka, Pawel P. Liberski, Piero Parchi, Shannon Sarros, Jacqueline M. Linehan, Sebastian Brandner, Maurizio Pocchiari, Ahmed P, Michael D. Geschwind, Fronztek K, Antonio Salas, Inga Zerr, Janis Blevins, Elodie Bouaziz-Amar, Brian S. Appleby, Steven J. Collins, P. Gambetti, Hata Karamujić-Čomić, Adriano Aguzzi, Philippe Amouyel, van der Lee S, Penny Norsworthy, Parmjit S. Jat, Liam Quinn, Emmanuelle Viré, and Simon Mead
Subjects: Genetics, 0303 health sciences, biology, animal diseases, Tau protein, STX6, Single-nucleotide polymorphism, Genome-wide association study, medicine.disease, 3. Good health, Progressive supranuclear palsy, PRNP, nervous system diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, biology.protein, Gene, 030217 neurology & neurosurgery, Exome sequencing, 030304 developmental biology
Abstract: Mammalian prions are lethal pathogens composed of fibrillar assemblies of misfolded prion protein. Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the gene that encodes prion protein (PRNP) are strong risk factors for sCJD, but although the condition has heritability similar to other neurodegenerative disorders, no other risk loci have yet been confirmed. By genome-wide association in European ancestry populations, we found three replicated loci (cases n=5208, within PRNP, STX6, and GAL3ST1) and two further unreplicated loci were significant in gene-wide tests (within PDIA4, BMERB1). Exome sequencing in 407 sCJD cases, conditional and transcription analyses suggest that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 and PDIA4 associate with increased expression of the major transcripts in disease-relevant brain regions. Alteration of STX6 expression does not modify prion propagation in a neuroblastoma cell model of mouse prion infection. We went on to analyse the proteins histologically in diseased tissue and examine the effects of risk variants on clinical phenotypes using deep longitudinal clinical cohort data. Risk SNPs in STX6, a protein involved in the intracellular trafficking of proteins and vesicles, are shared with progressive supranuclear palsy, a neurodegenerative disease associated with the misfolded protein tau. We present the first evidence of statistically robust associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism.
Published: 2020
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4. 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
Published: 2016
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5. Convergent genetic and expression data implicate immunity in Alzheimer's disease

Author: John R. Gilbert, Simon Lovestone, Diana Zelenika, Walter A. Kukull, Peter Passmore, Chiao-Feng Lin, Nathalie Fievet, Brian W. Kunkle, Dominique Campion, Philip L. De Jager, Adam C. Naj, Kara L. Hamilton-Nelson, Lina Keller, Jean-Charles Lambert, Denise Harold, Paul K. Crane, John Powell, Kathryn L. Lunetta, Paolo Caffarra, Lei Yu, Anthony Bayer, Tricia A. Thornton-Wells, Christiane Reitz, Eric B. Larson, Florentino Sanchez Garcia, Lindsay A. Farrer, Charlene Thomas, Ekaterina Rogaeva, Victoria Alavarez, Alfredo Ramirez, Pascale Barberger-Gateau, Dan Rujescu, Paul Hollingworth, Margaret A. Pericak-Vance, Daniela Galimberti, J. Kornhuber, Alexey Vedernikov, Philippe Amouyel, Peter Holmans, Gianfranco Spalletta, Carole Dufouil, Wolfgang Maier, Patrick G. Kehoe, Florence Pasquier, Lesley Jones, Harald Hampel, Stephen Todd, Valur Emilsson, Pau Pastor, Manuel Mayhaus, Claudine Berr, Seth Love, Michelangelo Mancuso, Mikko Hiltunen, Simon Mead, Hilkka Soininen, Vincent Deramecourt, Bernadette McGuinness, Magda Tsolaki, Jean-François Dartigues, Jordi Clarimón, Marie-Thérèse Bihoreau, Laura Fratiglioni, Duane Beekly, Sabrina Pichler, Caroline Graff, Albert V. Smith, Nick C. Fox, Amy Gerrish, Karen Ritchie, Carlos Cruchaga, John Hardy, Benedetta Nacmias, Maria Candida Deniz Naranjo, Christine Van Broeckhoven, Laura B. Cantwell, Minerva M. Carrasquillo, Richard Mayeux, Karolien Bettens, Vincent Chouraki, Clive Holmes, Thomas H. Mosley, David C. Rubinsztein, Gyungah Jun, Anita L. DeStefano, Lenore J. Launer, Alexander Richards, Jerome I. Rotter, Lars Lannfelt, Annette L. Fitzpatrick, Fanggeng Zou, Joseph D. Buxbaum, Cristina Razquin, Mercè Boada, Najaf Amin, Palmi V. Jonsson, Martin Dichgans, Thomas J. Montine, Yoichiro Kamatani, Debby W. Tsuang, Alexis Brice, Hakon Hakonarson, John Collinge, Albert Hofman, Eden R. Martin, Oscar L. Lopez, Olivier Hanon, Melanie L. Dunstan, Kevin Morgan, Nicola Jones, Cornelia M. van Duijn, Valentina Escott-Price, Vilmundur Gudnason, Susanne Moebus, Peter St George-Hyslop, Michael Conlon O'Donovan, Michael Gill, Tim Becker, Markus M. Nöthen, Sandro Sorbi, Céline Bellenguez, Mike A. Nalls, Martin Ingelsson, Otto Valladares, Kristel Sleegers, Sudha Seshadri, Gerard D. Schellenberg, María J. Bullido, Patrizia Mecocci, Eric Boerwinkle, Michael John Owen, Helena Schmidt, Kristelle Brown, Julie Williams, Renée F.A.G. de Bruijn, Jonathan L. Haines, Mark Lathrop, Maria Del Zompo, Denis A. Evans, Rebecca Sims, Badri N. Vardarajan, John S. K. Kauwe, Luc Letteneur, Agustín Ruiz, David Craig, Steven G. Younkin, Bruce M. Psaty, Ignacio Mateo, Tatiana Foroud, David Wallon, P. Bosco, Alberti Lleò, Amanda J. Myers, Alberto Pilotto, Petra Proitsi, Reinhold Schmidt, Matthew J. Huentelman, David A. Bennett, Onofre Combarros, Kelley Faber, Gudny Eiriksdottir, M. Arfan Ikram, Lluís Tárraga, Francesco Panza, Carla A. Ibrahim-Verbaas, Joshua C. Bis, Li-San Wang, Matthias Riemenschneider, Gary W. Beecham, Alison Goate, Seung Hoan Choi, John Gallacher, Robert Clarke, Didier Hannequin, Deborah Blacker, Frank Jessen, Christophe Tzourio, Tamara B. Harris, Benjamin Grenier-Boley, Paola Bossù, Janet A. Johnston, M. Ilyas Kamboh, Giancarlo Russo, Timothy Stone, Carol Brayne, Eliecer Coto, French National Foundation on Alzheimer’s Disease and Related Disorders, Institut Pasteur, National Institutes of Health (US), Centre National de Genotypage (France), Fédération pour la Recherche sur le Cerveau (France), Erasmus University Rotterdam, Medical Research Council (UK), International Genomics of Alzheimer's Disease Consortium (IGAP), Neurology, and Epidemiology
Subjects: Pathway analysis, Epidemiology, ALIGATOR, Alzheimer's disease, Cholesterol metabolism, Dementia, Endocytosis, Immune response, Neurodegeneration, Ubiquitination, Weighted gene co-expression network analysis, Medizin, Genome-wide association study, genetics [Alzheimer Disease], Gene expression, Genetics, education.field_of_study, Health Policy, Brain, Single Nucleotide, 3. Good health, Psychiatry and Mental Health, Algorithms, Alzheimer Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Cellular and Molecular Neuroscience, Alzheimer’s disease, metabolism [Alzheimer Disease], Population, Genomics, Biology, Aligator, Article, Biological pathway, SDG 3 - Good Health and Well-being, medicine, ddc:610, Polymorphism, education, medicine.disease, Protein ubiquitination, metabolism [Brain], Human medicine
Abstract: © 2015, Elsevier Inc. All rights reserved. Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10-12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10-11), cholesterol transport (P = 2.96 × 10-9), and proteasome-ubiquitin activity (P = 1.34 × 10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P =.002-.05). Conclusions: The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics., Medical Research Council, Alzheimer’s Research UK, and theWelsh Assembly Government. ADGC and CHARGE were supported by the National Institutes of Health, National Institute on Aging (NIH-NIA). CHARGE was also supported by Erasmus Medical Center and Erasmus University. IGAP was funded by the French National Foundation on Alzheimer’s Disease and Related Disorders, the Centre National de Genotypage and the Institut Pasteur de Lille, Inserm, FRC (Fondation pour la Recherche sur le Cerveau), and Rotary. This work has been developed and supported by the LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease).
Published: 2015
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6. A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

Author: Anais Mounier, James T. Becker, Vincent Chouraki, Robert S. Rogers, P. Amouyel, Florie Demiautte, R. F. A. G. de Bruijn, Richard Mayeux, Annette L. Fitzpatrick, J. C. Bis, J. F. Dartigues, Carla A. Ibrahim-Verbaas, A. Hofman, Christophe Tzourio, Benjamin Grenier-Boley, M. A. Ikram, Mark Lathrop, A.G. Uitterlinden, Oscar L. Lopez, Claudine Berr, Nicole Schupf, M.M.B. Breteler, Christiane Reitz, Annick Alpérovitch, J-C Lambert, C M van Duijn, Susanna Schraen, Luc Buée, Charlotte Delay, and Julien Chapuis
Subjects: Aging, Amyloid beta, Locus (genetics), Genome-wide association study, Biology, Polymorphism, Single Nucleotide, APP protein, human, White People, Article, Cellular and Molecular Neuroscience, Amyloid beta-Protein Precursor, SDG 3 - Good Health and Well-being, blood [Amyloid beta-Peptides], metabolism [Amyloid beta-Protein Precursor], blood [Aging], medicine, Humans, ddc:610, Senile plaques, Molecular Biology, Gene, Amyloid beta-Peptides, CTXN3 protein, human, HEK 293 cells, Membrane Proteins, amyloid beta-protein (1-40), amyloid beta-protein (1-42), medicine.disease, Peptide Fragments, genetics [European Continental Ancestry Group], genetics [Membrane Proteins], Psychiatry and Mental health, HEK293 Cells, Membrane protein, Biochemistry, genetics [Amyloid beta-Protein Precursor], blood [Peptide Fragments], genetics [Aging], biology.protein, Alzheimer's disease, metabolism [Membrane Proteins], Genome-Wide Association Study
Abstract: Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ 1-40 and Aβ 1 -42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P
Published: 2014
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7. Polygenic scores associated with educational attainment in adults predict educational achievement and ADHD symptoms in children

Author: Sang Hong Lee, Danielle Posthuma, Debbie A Lawlor, Michael B. Miller, Igor Rudan, Jürgen Wellmann, François Bastardot, Lawrence F. Bielak, Anu Realo, William G. Iacono, Lude Franke, Matthew Kowgier, Marika Kaakinen, Helena Schmidt, Jorma Viikari, Jennifer A. Smith, David R. Van Wagoner, Elizabeth G. Holliday, Veronique Vitart, Robert F. Krueger, Pamela A. F. Madden, Jan Emmanuel De, Andrew Heath, David Cesarini, Najaf Amin, Dale R. Nyholt, Juliette Harris, Nicholas J. Timpson, George Dedoussis, Stefania Bandinelli, W. Hoffmann, Albert V. Smith, Beate St Pourcain, Stavroula Kanoni, Martin F. Elderson, Maria Dimitriou, Jouke-Jan Hottenga, Min A. Jhun, Daniel S. Evans, Marjo-Riitta Järvelin, Lei Yu, Krista Fischer, Jae Hoon Sul, Jennifer R. Harris, Brenda W.J.H. Penninx, Antti-Pekka Sarin, Ida Surakka, Arpana Agrawal, Bo Jacobsson, Klaus Berger, Matt McGue, Christopher F. Chabris, Marisa Loitfelder, Veikko Salomaa, David Schlessinger, Mina K. Chung, Erik A. Ehli, Kati Kristiansson, Eva Albrecht, Niina Eklund, Aarno Palotie, Sarah E. Medland, Reinhold E. Schmidt, Kurt Lohman, Luigi Ferrucci, Osorio Meirelles, Ivana Kolcic, Vilmundur Gudnason, Nicholas G. Martin, Tomi E. Mäkinen, Robert M. Kirkpatrick, Thomas Illig, Peter M. Visscher, Håkon K. Gjessing, Sebastian E. Baumeister, Carla A. Ibrahim-Verbaas, Per Hall, Elisabeth Widen, Panos Deloukas, Ronny Myhre, Michelle N. Meyer, Jonathan P. Beauchamp, Caroline Hayward, Eveline L. de Zeeuw, Penelope A. Lind, Erik Ingelsson, Ian J. Deary, George Davey-Smith, Dalton Conley, Peter Lichtner, Cornelia M. van Duijn, Samuli Ripatti, Dena G. Hernandez, Albert Hofman, George McMahon, Thais S. Rizzi, Wei Zhao, Patrick K.E. Magnusson, Jingmei Li, Mariza de Andrade, Ben A. Oostra, Abdel Abdellaoui, Andres Metspalu, Patricia A. Peyser, Jessica D. Faul, David C. Liewald, Christina Holzapfel, Lydia Quaye, John Barnard, Meike Bartels, Christian Gieger, John P. Rice, Christiaan de Leeuw, Patricia A. Boyle, Nicholas D. Hastie, David R. Weir, Adriaan Hofman, Astanand Jugessur, Tamara B. Harris, Catharina E. M. van Beijsterveldt, Gail Davies, H.-Erich Wichmann, Lynn Cherkas, Polasek Ozren Polasek, Harm-Jan Westra, Yongmei Liu, Jari Lahti, Matthijs J. H. M. van der Loos, Rodney J. Scott, Gérard Waeber, Peter Vollenweider, Behrooz Z. Alizadeh, Frank J. A. van Rooij, Susan M. Ring, Judith M. Vonk, Lyle J. Palmer, Alexander Teumer, John M. Starr, Antonio Terracciano, Sara Hägg, Erkki Vartiainen, David Laibson, Eco J. C. de Geus, Mika Kähönen, Marco Masala, Peng Lin, Nicolas W. Martin, André G. Uitterlinden, Dorret I. Boomsma, Harry Campbell, Sutapa Mukherjee, Konstantin Shakhbazov, Henning Tiemeier, Zó Ltan Kutalik, Grant W. Montgomery, Eva Reinmaa, Aldo Rustichini, Wouter J. Peyrot, David M. Evans, Martin Preisig, Cornelius A. Rietveld, T.J. Glasner, J Kaprio, John Attia, Pedro Marques Vidal, Sharon L.R. Kardia, Peter K. Joshi, Toshiko Tanaka, Rauli Svento, Magnus Johannesson, Terho Lethimäki, Jüri Allik, Philip L. De Jager, Antti Latvala, Marja-Liisa Nuotio, Juha Karjalainen, Henry Völzke, Roy Thurik, Rolf Holle, Kelly S. Benke, Christopher Oldmeadow, Esko Toñu Esko, Johan G. Eriksson, Alan F. Wright, Francesco Cucca, Ute Bültmann, Olli T. Raitakari, Melissa E. Garcia, Patrick J. F. Groenen, Maria M. Groen-Blokhuis, Gonneke Willemsen, Jian Yang, Lili Milani, Fernando Rivadeneira, David A. Bennett, Gudny Eiriksdottir, Katri Räikkönen, Harold Snieder, Laura J. Bierut, James J. Hudziak, James F. Wilson, Rudolf S N Fehrmann, Jaime Derringer, Gareth E. Davies, K. Petrovic, Markus Perola, Lenore J. Launer, Daniel J. Benjamin, Paul Lichtenstein, Philipp Koellinger, Andreas Mielck, Jeffrey A. Boatman, Henrik Grönberg, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Public Health Research (PHR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), EMGO+ - Mental Health, Biological Psychology, Methods and Techniques, Child and Adolescent Psychiatry / Psychology, Ophthalmology, and Epidemiology
Subjects: Netherlands Twin Register (NTR), Multifactorial Inheritance, genetic association, genotype, Academic achievement, Educational achievement, single nucleotide polymorphism, genetic variability, Genetics (clinical), Netherlands, child, article, symptom, academic achievement, Psychiatry and Mental health, priority journal, achievement test, Regression Analysis, Psychology, SDG 4 - Quality Education, Clinical psychology, Adult, phenotype, effect size, attention deficit disorder, gene frequency, educational status, Cellular and Molecular Neuroscience, reading, study skills, mental disorders, Genetics, medicine, Humans, ADHD, Attention deficit hyperactivity disorder, Achievement test, controlled study, human, Association (psychology), Genetic association, attention disturbance, language, School performance, medicine.disease, arithmetic, major clinical study, Polygenic scores, Educational attainment, gene linkage disequilibrium, Attention Deficit Disorder with Hyperactivity, Study skills
Abstract: The American Psychiatric Association estimates that 3 to 7 per cent of all school aged children are diagnosed with attention deficit hyperactivity disorder (ADHD). Even after correcting for general cognitive ability, numerous studies report a negative association between ADHD and educational achievement. With polygenic scores we examined whether genetic variants that have a positive influence on educational attainment have a protective effect against ADHD. The effect sizes from a large GWA meta-analysis of educational attainment in adults were used to calculate polygenic scores in an independent sample of 12-year-old children from the Netherlands Twin Register. Linear mixed models showed that the polygenic scores significantly predicted educational achievement, school performance, ADHD symptoms and attention problems in children. These results confirm the genetic overlap between ADHD and educational achievement, indicating that one way to gain insight into genetic variants responsible for variation in ADHD is to include data on educational achievement, which are available at a larger scale. (C) 2014 Wiley Periodicals, Inc.
Published: 2014
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8. The sex-specific associations of the aromatase gene with Alzheimer's disease and its interaction with IL10 in the Epistasis Project

Author: Kristelle Brown, Helen Butler, C M van Duijn, Naomi Hammond, A. D. Smith, Mario Cortina-Borja, Rachel Barber, de Bruijn Rfag., Christopher Medway, Mohammad Arfan Ikram, Gordon K. Wilcock, Eliecer Coto, Ignacio Mateo, Pascual Sánchez-Juan, Onofre Combarros, Patrick G. Kehoe, R. Heun, D J Lehmann, Peter J. Koudstaal, Heike Kölsch, Panagiotis Deloukas, Olivia Belbin, Kevin Morgan, Donald Warden, Michael G Lehmann, Victoria Alvarez, Carla A. Ibrahim-Verbaas, Neurology, Epidemiology, and Radiology & Nuclear Medicine
Subjects: Male, Risk, medicine.medical_specialty, Linkage disequilibrium, Estrogen receptor, Disease, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Article, Aromatase, Gene Frequency, Alzheimer Disease, Internal medicine, Odds Ratio, Genetics, medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Genetics (clinical), Aged, Aged, 80 and over, Sex Characteristics, Case-control study, Epistasis, Genetic, Odds ratio, medicine.disease, Interleukin-10, Endocrinology, Case-Control Studies, biology.protein, Epistasis, Female, Alzheimer's disease
Abstract: Epistasis between interleukin-10 (IL10) and aromatase gene polymorphisms has previously been reported to modify the risk of Alzheimer's disease (AD). However, although the main effects of aromatase variants suggest a sex-specific effect in AD, there has been insufficient power to detect sex-specific epistasis between these genes to date. Here we used the cohort of 1757 AD patients and 6294 controls in the Epistasis Project. We replicated the previously reported main effects of aromatase polymorphisms in AD risk in women, for example, adjusted odds ratio of disease for rs1065778 GG = 1.22 (95% confidence interval: 1.01-1.48, P=0.03). We also confirmed a reported epistatic interaction between IL10 rs1800896 and aromatase (CYP19A1) rs1062033, again only in women: adjusted synergy factor = 1.94 (1.16-3.25, 0.01). Aromatase, a rate-limiting enzyme in the synthesis of estrogens, is expressed in AD-relevant brain regions,and is downregulated during the disease. IL-10 is an anti-inflammatory cytokine. Given that estrogens have neuroprotective and anti-inflammatory activities and regulate microglial cytokine production, epistasis is biologically plausible. Diminishing serum estrogen in postmenopausal women, coupled with suboptimal brain estrogen synthesis, may contribute to the inflammatory state, that is a pathological hallmark of AD.
Published: 2014
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9. Intensity of human prion disease surveillance predicts observed disease incidence

Author: Maren Breithaupt, Inga Zerr, Annick Alpérovitch, Robert G. Will, Steven J. Collins, Gerard H. Jansen, Rachel Howley, Marion Simpson, Michael Farrell, Michael Coulthard, Genevieve M Klug, Cornelia M. van Duijn, Handan Wand, Alison Boyd, Colin L. Masters, Jean-Philippe Brandel, Matthew Law, Gabor G. Kovacs, Jan Mackenzie, Herbert Budka, Radoslav Matěj, Carla A. Ibrahim-Verbaas, University of Zurich, Klug, Genevieve M J A, Epidemiology, and Neurology
Subjects: Canada, Pediatrics, medicine.medical_specialty, Population, 10208 Institute of Neuropathology, Surveillance Methods, 610 Medicine & health, Disease, Creutzfeldt-Jakob Syndrome, Prion Diseases, 2738 Psychiatry and Mental Health, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Public health surveillance, Epidemiology, medicine, Humans, Dementia, Public Health Surveillance, Registries, 030212 general & internal medicine, education, Psychiatry, Disease surveillance, education.field_of_study, business.industry, Incidence, Incidence (epidemiology), Australia, medicine.disease, 2746 Surgery, nervous system diseases, 3. Good health, Europe, Psychiatry and Mental health, 2728 Neurology (clinical), Epidemiological Monitoring, 570 Life sciences, biology, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background Prospective national screening and surveillance programmes serve a range of public health functions. Objectively determining their adequacy and impact on disease may be problematic for rare disorders. We undertook to assess whether objective measures of disease surveillance intensity could be developed for the rare disorder sporadic Creutzfeldt–Jakob disease (CJD) and whether such measures correlate with disease incidence. Method From 10 countries with national human prion disease surveillance centres, the annual number of suspected prion disease cases notified to each national unit (n=17 610), referrals for cerebrospinal fluid (CSF) 14-3-3 protein diagnostic testing (n=28 780) and the number of suspect cases undergoing diagnostic neuropathological examination (n=4885) from 1993 to 2006 were collected. Age and survey year adjusted incidence rate ratios with 95% CIs were estimated using Poisson regression models to assess risk factors for sporadic, non-sporadic and all prion disease cases. Results Age and survey year adjusted analysis showed all three surveillance intensity measures (suspected human prion disease notifications, 14-3-3 protein diagnostic test referrals and neuropathological examinations of suspect cases) significantly predicted the incidence of sporadic CJD, non-sporadic CJD and all prion disease. Conclusions Routine national surveillance methods adjusted as population rates allow objective determination of surveillance intensity, which correlates positively with reported incidence for human prion disease, especially sporadic CJD, largely independent of national context. The predictive relationship between surveillance intensity and disease incidence should facilitate more rapid delineation of aberrations in disease occurrence and assessment of the adequacy of disease monitoring by national registries.
Published: 2013
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10. Evaluation of a Genetic Risk Score to Improve Risk Prediction for Alzheimer's Disease

Author: Annette L. Fitzpatrick, P. Amouyel, Richard Mayeux, Johanna Jakobsdottir, Hieab H.H. Adams, Anita L. DeStefano, Badri N. Vardarajan, Chouraki, de Jager Pl, David A. Bennett, Jean-François Dartigues, Shubhabrata Mukherjee, Seung Hoan Choi, M. A. Ikram, Christiane Reitz, Eric B. Larson, Oscar L. Lopez, Fleur Maury, Jean-Charles Lambert, Sudha Seshadri, Lei Yu, van der Lee Sj, Albert Hofman, van Duijn C, J. C. Bis, Gudnason, L. J. Launer, A.G. Uitterlinden, Carla A. Ibrahim-Verbaas, Paul K. Crane, Céline Bellenguez, Claudine Berr, Epidemiology, Internal Medicine, and Neurology
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Apolipoprotein E4, Genome-wide association study, Neuropsychological Tests, Polymorphism, Single Nucleotide, Risk Assessment, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Predictive Value of Tests, Risk Factors, Internal medicine, Statistics, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Genetic testing, Aged, Proportional Hazards Models, Aged, 80 and over, Psychiatric Status Rating Scales, Framingham Risk Score, medicine.diagnostic_test, business.industry, Proportional hazards model, General Neuroscience, Hazard ratio, General Medicine, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Meta-analysis, Educational Status, Female, Geriatrics and Gerontology, business, Risk assessment, 030217 neurology & neurosurgery, Cohort study, Genome-Wide Association Study
Abstract: Effective prevention of Alzheimer's disease (AD) requires the development of risk prediction tools permitting preclinical intervention. We constructed a genetic risk score (GRS) comprising common genetic variants associated with AD, evaluated its association with incident AD and assessed its capacity to improve risk prediction over traditional models based on age, sex, education, and APOE epsilon 4. In eight prospective cohorts included in the International Genomics of Alzheimer's Project (IGAP), we derived weighted sum of risk alleles from the 19 top SNPs reported by the IGAPGWAS in participants aged 65 and older without prevalent dementia. Hazard ratios (HR) of incident AD were estimated in Cox models. Improvement in risk prediction was measured by the difference in C-index (Delta-C), the integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI>0). Overall, 19,687 participants at risk were included, of whom 2,782 developed AD. The GRS was associated with a 17% increase in AD risk (pooled HR=1.17; 95% CI = [1.13-1.21] per standard deviation increase in GRS; p-value = 2.86x10(-16)). This association was stronger among persons with at least one APOE epsilon 4 allele (HRGRS = 1.24; 95% CI = [1.15-1.34]) than in others (HRGRS = 1.13; 95% CI = [1.08-1.18]; p(interaction) = 3.45x10(-2)). Risk prediction after seven years of follow-up showed a small improvement when adding the GRS to age, sex, APOE epsilon 4, and education (Delta-Cindex = 0.0043 [0.0019-0.0067]). Similar patterns were observed for IDI and NRI>0. In conclusion, a risk score incorporating common genetic variation outside the APOE epsilon 4 locus improved AD risk prediction and may facilitate risk stratification for prevention trials.
Published: 2016

11. Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease

Author: Johanna Jakobsdottir, Sven J van der Lee, Joshua C Bis, Vincent Chouraki, David Li-Kroeger, Shinya Yamamoto, Megan L Grove, Adam Naj, Maria Vronskaya, Jose L Salazar, Anita L DeStefano, Jennifer A Brody, Albert V Smith, Najaf Amin, Rebecca Sims, Carla A Ibrahim-Verbaas, Seung-Hoan Choi, Claudia L Satizabal, Oscar L Lopez, Alexa Beiser, M Arfan Ikram, Melissa E Garcia, Caroline Hayward, Tibor V Varga, Samuli Ripatti, Paul W Franks, Göran Hallmans, Olov Rolandsson, Jan-Håkon Jansson, David J Porteous, Veikko Salomaa, Gudny Eiriksdottir, Kenneth M Rice, Hugo J Bellen, Daniel Levy, Andre G Uitterlinden, Valur Emilsson, Jerome I Rotter, Thor Aspelund, Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, Alzheimer’s Disease Genetic Consortium, Genetic and Environmental Risk in Alzheimer’s Disease consortium, Christopher J O'Donnell, Annette L Fitzpatrick, Lenore J Launer, Albert Hofman, Li-San Wang, Julie Williams, Gerard D Schellenberg, Eric Boerwinkle, Bruce M Psaty, Sudha Seshadri, Joshua M Shulman, Vilmundur Gudnason, Cornelia M van Duijn, Epidemiology, Neurology, Radiology & Nuclear Medicine, Internal Medicine, VU University medical center, Clinicum, Institute for Molecular Medicine Finland, Samuli Olli Ripatti / Principal Investigator, Department of Public Health, Biostatistics Helsinki, Complex Disease Genetics, and Haines, Jonathan L
Subjects: Male, Apolipoprotein E, Genetic and Environmental Risk in Alzheimer’s Disease consortium, Aging, PROTEIN, Social Sciences, Genome-wide association study, Tropomyosin, Alzheimer's Disease, Cell Signaling, Sociology, Age of Onset, Aetiology, MUTATION, Notch Signaling, Drosophila Melanogaster, Intracellular Signaling Peptides and Proteins, COMMON VARIANTS, Genomics, Phenotypes, Drosophila melanogaster, Neurology, medicine.medical_specialty, Notch, European Continental Ancestry Group, White People, APOLIPOPROTEIN-E, Presenilin, 03 medical and health sciences, Apolipoproteins E, SDG 3 - Good Health and Well-being, Clinical Research, Alzheimer Disease, Genetics, Humans, Rare functional variant, GENOME-WIDE ASSOCIATION, Molecular Biology, Alleles, Ecology, Evolution, Behavior and Systematics, Aged, Embryos, Organisms, Correction, Biology and Life Sciences, Odds ratio, Invertebrates, 030104 developmental biology, Endocrinology, Genetic Loci, Mutation, Dementia, Developmental Biology, 0301 basic medicine, Embryology, Cancer Research, Iceland, Neurodegenerative, QH426-470, Amyloid beta-Protein Precursor, Alzheimer’s Disease Genetic Consortium, Consortia, Receptors, Invertebrate Genomics, Medicine and Health Sciences, Drosophila Proteins, 2.1 Biological and endogenous factors, Exome, DROSOPHILA-MELANOGASTER DEVELOPMENT, Genetics (clinical), Receptors, Notch, Neurodegenerative Diseases, Animal Models, Insects, Phenotype, Neurological, Female, Drosophila, Neurovetenskaper, Research Article, Signal Transduction, Arthropoda, UNITED-STATES, Late onset, Biology, Research and Analysis Methods, IDENTIFIES VARIANTS, Model Organisms, Internal medicine, Mental Health and Psychiatry, Acquired Cognitive Impairment, medicine, Animals, Allele, HAPLOTYPE RECONSTRUCTION, Human Genome, Neurosciences, Membrane Proteins, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Cell Biology, Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, Brain Disorders, Animal Genomics, RC0321, 3111 Biomedicine, Age of onset, Genome-Wide Association Study
Abstract: We performed an exome-wide association analysis in 1393 late-onset Alzheimer’s disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus, Author Summary Alzheimer’s disease (AD) is the most common cause of dementia in the older adult population. There is substantial evidence for an important genetic contribution to AD risk. While prior work has comprehensively evaluated the contribution of common genetic variants in large population-based cohorts, the role of rare variants remains to be defined. Here, we have used a newer genotyping array to characterize less common variants, including those likely to impact the function of encoded proteins, in a combined cohort of 1393 AD cases and 8141 control subjects without AD. Our results implicate a novel, amino acid-changing variant, P155L, in the TM2D3 gene. This variant was discovered to be more common in the Icelandic population, where it was significantly associated with both increased risk and earlier age of onset of AD. Lastly, in order to examine the potential functional impact of the implicated variant, we performed additional studies in the fruit fly. Our results suggest that P155L causes a loss-of-function in TM2D3, in the context of Notch-Presenilin signal transduction. In sum, we identify a novel, rare TM2D3 variant in association with AD risk and highlight functional connections with AD-relevant biology.
Published: 2016
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12. The association between lower educational attainment and depression owing to shared genetic effects?: Results in ~25,000 subjects

Author: Patricia A. Peyser, Jessica D. Faul, Patrik K. E. Magnusson, Nicholas D. Hastie, Beate St Pourcain, Marcus Ising, Gérard Waeber, Behrooz Z. Alizadeh, Judith M. Vonk, Lawrence F. Bielak, Sang Hong Lee, Wouter J. Peyrot, Thomas Illig, M. M. Weissman, Nicholas J. Timpson, George Dedoussis, Nicholas G. Martin, Tomi E. Mäkinen, Jorma Viikari, Lili Milani, Harold Snieder, Laura J. Bierut, A. C. Heath, Reinhold E. Schmidt, Mariza de Andrade, Vilmundur Gudnason, K. Petrovic, Robert M. Kirkpatrick, Marcela González Gross, William G. Iacono, Michelle N. Meyer, Henry Völzke, Marisa Loitfelder, Maria Dimitriou, Lude Franke, Robert F. Krueger, E. J. C. G. van den Oord, Sven Cichon, Michael Conlon O'Donovan, Ian W. Craig, Shawn N. Murphy, Danielle Posthuma, Brenda W.J.H. Penninx, Aarno Palotie, Roy Thurik, Panos Deloukas, Matt McGue, M. Preisig, Patricia A. Boyle, Osorio Meirelles, Ben A. Oostra, Klaus Berger, G. M. Montgomery, Sharon L.R. Kardia, Peter K. Joshi, K. Stefansson, Paul Lichtenstein, Andrew Heath, Andrea Schulz, Dena G. Hernandez, Debbie A Lawlor, S. P. Hamilton, James B. Potash, Z. Kutalik, Elisabeth Widen, Emil L. Sigurdsson, Rudolf S N Fehrmann, Matthias Nauck, Mikael Landén, Kurt Lohman, S.D. Gordon, Lefkos T. Middleton, Caroline Hayward, Anjali K. Henders, Philipp Koellinger, Jeffrey A. Boatman, G van Grootheest, M. Daly, Jian Yang, Peter Vollenweider, Penelope A. Lind, Stacy Steinberg, Frank J. A. van Rooij, Florian Holsboer, Hkon K. Gjessing, Erkki Vartiainen, Magnus Johannesson, Jingmei Li, David Laibson, Henrik Grönberg, Tõnu Esko, Ivana Kolcic, Niina Eklund, Kelly S. Benke, Henning Tiemeier, Isaac S. Kohane, Nicolas W. Martin, Ronny Myhre, Frans G. Zitman, Arpana Agrawal, James F. Wilson, Michael R. Barnes, Lei Yu, Thorgeir E. Thorgeirsson, Franois Bastardot, Katri Räikkönen, William Lawson, Willem A. Nolen, M. Rietschel, René Breuer, Bertram Müller-Myhsok, James A. Knowles, Grant W. Montgomery, Eva Reinmaa, Rudolf Uher, Andreas Mielck, Luigi Ferrucci, S. E. Medland, Yuri Milaneschi, Philip L. De Jager, Manfred Uhr, A. E. Farmer, Cornelia M. van Duijn, Samuli Ripatti, Marja-Liisa Nuotio, Manuel Mattheisen, Sebastian E. Baumeister, David R. Van Wagoner, Martin Preisig, Fernando Rivadeneira, Peter Lichtner, Christopher Oldmeadow, Hreinn Stefansson, Ian B. Hickie, Darina Czamara, Elizabeth G. Holliday, Astanand Jugessur, Carla A. Ibrahim-Verbaas, Jaime Derringer, Vivian S. Gainer, P. Muglia, Daniel J. Benjamin, Patrick K.E. Magnusson, Patience J. Gallagher, Jennifer A. Smith, Lynn Cherkas, Pamela A. F. Madden, David A. Bennett, Zoltán Kutalik, George Davey-Smith, Gudny Eiriksdottir, Jens Treutlein, N. Craddock, Juliette Harris, Antti Latvala, Roy H. Perlis, Markus M. Noethen, Jan-Emmanuel De Neve, Stanley I. Shyn, J.H. Smit, Dalton Conley, Adriaan Hofman, Jari Lahti, Patrick J. F. Groenen, Jüri Allik, Albert V. Smith, Ozren Polasek, Susan M. Ring, Thomas Bettecken, Michele L. Pergadia, Patrick J. McGrath, Katherine E. Tansey, Stephan Ripke, Hogni Oskarsson, Peng Lin, Douglas F. Levinson, Matthijs J. H. M. van der Loos, Melissa E. Garcia, Jonathan P. Beauchamp, Rodney J. Scott, Zhihong Zhu, Michel Guipponi, Lyle J. Palmer, Alexander Teumer, William Coryell, Stefan Kloiber, Gonneke Willemsen, John Frank, Victor M. Castro, Andrew M. McIntosh, John M. Starr, Antonio Terracciano, Mika Kähönen, Marco Masala, Markus Perola, André G. Uitterlinden, Sutapa Mukherjee, Alexander Viktorin, Lenore J. Launer, Elisabeth B. Binder, William A. Scheftner, Christel M. Middeldorp, D. H. R. Blackwood, I. Jones, Thais S. Rizzi, A. Teumer, Cornelius A. Rietveld, Aldo Rustichini, Guy Lewis, Susan L. Slager, David M. Evans, Dorret I. Boomsma, Harry Campbell, Susanne Churchill, Johan G. Eriksson, Alan F. Wright, Dan V. Iosifescu, W. Maier, Francesco Cucca, Federica Tozzi, David R. Weir, Eva Albrecht, L. Milani, Jennifer R. Harris, Min A. Jhun, Marjo-Riitta Järvelin, Martin F. Elderson, Ute Bültmann, Olli T. Raitakari, Konstantin Shakhbazov, Krista Fischer, Thomas G. Schulze, T. Jung-Ying, P. Lichtenstein, Terho Lethimäki, Jeffrey B. Weilburg, Rolf Holle, Bo Jacobsson, Pedro Marques Vidal, Jordan W. Smoller, Stavroula Kanoni, Kati Kristiansson, Sergey Goryachev, Michael Steffens, Peter M. Visscher, Toshiko Tanaka, Donald J. MacIntyre, Witte J.G. Hoogendijk, David Schlessinger, Ian J. Deary, Harm-Jan Westra, Erik Ingelsson, E.J.C. de Geus, Franziska Degenhardt, Lydia Quaye, John Barnard, David C. Liewald, John P. Rice, Christopher F. Chabris, P. McGuffin, Tamara B. Harris, C. M. Lewis, Gail Davies, Enda M. Byrne, H.-Erich Wichmann, Sara Hägg, David Cesarini, Najaf Amin, Juha Karjalainen, Dale R. Nyholt, Christian Gieger, Per Hall, Ania Korszun, Neale Bm, Wei Zhao, Abdel Abdellaoui, Andres Metspalu, Christina Holzapfel, Jae Hoon Sul, Christiaan de Leeuw, Antti-Pekka Sarin, Ida Surakka, Veikko Salomaa, Mina K. Chung, N. L. Pedersen, Gerome Breen, P. A. F. Madden, Martin A. Kohli, J Kaprio, John Attia, Jing Shi, Gibran Hemani, Rauli Svento, Veronique Vitart, Susanne Lucae, L. A. Jones, Jouke-Jan Hottenga, Daniel S. Evans, Hans-Jörgen Grabe, Yongmei Liu, Danyu Lin, Albert Hofman, George McMahon, Naomi R. Wray, Stefan Herms, Stefania Bandinelli, W. Hoffmann, P.F. Sullivan, Susanne Hoefels, Michael B. Miller, Alan W. McLean, Igor Rudan, Jürgen Wellmann, Anu Realo, Maurizio Fava, Matthew Kowgier, Marika Kaakinen, Helena Schmidt, Faculteit Medische Wetenschappen/UMCG, Peyrot, WJ, Lee, SH, Milaneschi, Y, Abdellaoui, A, Penninx, BWJH, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Social Science Genetic Association Consortium, Psychiatry, NCA - Neurobiology of mental health, EMGO - Mental health, Applied Economics, Biological Psychology, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator), Social Science Genetic Association Consortium Corporate Collaborator, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium Corporate Collaborator, Lewis, C.M., Hamilton, S.P., Weissman, M.M., Breen, G., Blackwood, D.H., Cichon, S., Heath, A.C., Holsboer, F., Madden, P.A., McGuffin, P., Muglia, P., Pergadia, M.L., Lin, D., Müller-Myhsok, B., Steinberg, S., Grabe, H.J., Lichtenstein, P., Magnusson, P., Perlis, R.H., Preisig, M., Smoller, J.W., Stefansson, K., Uher, R., Kutalik, Z., Tansey, K.E., Teumer, A., Viktorin, A., Barnes, M.R., Bettecken, T., Binder, E.B., Breuer, R., Castro, V.M., Churchill, S.E., Coryell, W.H., Craddock, N., Craig, I.W., Czamara, D., Degenhardt, F., Farmer, A.E., Fava, M., Frank, J., Gainer, V.S., Gallagher, P.J., Gordon, S.D., Goryachev, S., Gross, M., Guipponi, M., Henders, A.K., Herms, S., Hickie, I.B., Hoefels, S., Hoogendijk, W., Iosifescu, D.V., Ising, M., Jones, I., Jones, L., Jung-Ying, T., Knowles, J.A., Kohane, I.S., Kohli, M.A., Korszun, A., Landen, M., Lawson, W.B., Lewis, G., Macintyre, D., Maier, W., Mattheisen, M., McGrath, P.J., McIntosh, A., McLean, A., Middeldorp, C.M., Middleton, L., Montgomery, G.M., Murphy, S.N., Nauck, M., Nolen, W.A., Nyholt, D.R., O'Donovan, M., Oskarsson, H., Pedersen, N., Scheftner, W.A., Schulz, A., Schulze, T.G., Shyn, S.I., Sigurdsson, E., Slager, S.L., Smit, J.H., Stefansson, H., Steffens, M., Thorgeirsson, T., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E.J., Van Grootheest, G., Völzke, H., Weilburg, J.B., Willemsen, G., Zitman, F.G., Neale, B., Daly, M., Sullivan, P.F., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Allik, J., Amin, N., Attia, J.R., Bandinelli, S., Barnard, J., Bastardot, F., Baumeister, S.E., Beauchamp, J., Benjamin, D.J., Benke, K.S., Bennett, D.A., Berger, K., Bielak, L.F., Bierut, L.J., Boatman, J.A., Boyle, P.A., Bültmann, U., Campbell, H., Cesarini, D., Chabris, C.F., Cherkas, L., Chung, M.K., Conley, D., Cucca, F., Davey-Smith, G., Davies, G., de Andrade, M., De Jager, P.L., de Leeuw, C., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Derringer, J., Dimitriou, M., Eiriksdottir, G., Eklund, N., Elderson, M.F., Eriksson, J.G., Evans, D.S., Evans, D.M., Faul, J.D., Fehrmann, R., Ferrucci, L., Fischer, K., Franke, L., Garcia, M.E., Gieger, C., Gjessing, H.K., Groenen, P.J., Grönberg, H., Gudnason, V., Hägg, S., Hall, P., Harris, J.R., Harris, J.M., Harris, T.B., Hastie, N.D., Hayward, C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Holzapfel, C., Iacono, W.G., Ibrahim-Verbaas, C.A., Illig, T., Ingelsson, E., Jacobsson, B., Järvelin, M.R., Jhun, M.A., Johannesson, M., Joshi, P.K., Jugessur, A., Kaakinen, M., Kähönen, M., Kanoni, S., Kaprio, J., Kardia, S.L., Karjalainen, J., Kirkpatrick, R.M., Koellinger, P.D., Kolcic, I., Kowgier, M., Kristiansson, K., Krueger, R.F., Lahti, J., Laibson, D., Latvala, A., Launer, L.J., Lawlor, D.A., Lethimäki, T., Li, J., Lichtner, P.K., Liewald, D.C., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., Magnusson, P.K., Mäkinen, T.E., Vidal, P.M., Martin, N.W., Masala, M., McGue, M., McMahon, G., Meirelles, O., Meyer, M.N., Mielck, A., Milani, L., Miller, M.B., Montgomery, G.W., Mukherjee, S., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Oostra, B.A., Palmer, L.J., Palotie, A., Perola, M., Petrovic, K.E., Peyser, P.A., Polašek, O., Posthuma, D., Quaye, L., Räikkönen, K., Raitakari, O.T., Realo, A., Reinmaa, E., Rice, J.P., Ring, S.M., Ripatti, S., Rivadeneira, F., Rizzi, T.S., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Schmidt, H., Schmidt, R., Scott, R.J., Shakhbazov, K., Smith, A.V., Smith, J.A., Snieder, H., Pourcain, B.S., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Tanaka, T., Terracciano, A., Thurik, A.R., Tiemeier, H., Timpson, N.J., Uitterlinden, A.G., van der Loos, M.J., van Duijn, C.M., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Visscher, P.M., Vitart, V., Vollenweider, P.K., Vonk, J.M., Waeber, G., Weir, D.R., Wellmann, J., Westra, H.J., Wichmann, H.E., Widen, E., Wilson, J.F., Wright, A.F., Yang, J., Yu, L., and Zhao, W.
Subjects: Netherlands Twin Register (NTR), Male, Genome-wide association study, Logistic regression, Cohort Studies, Odds Ratio, pleiotropic genetic effects, Netherlands, Psychiatry, education.field_of_study, Likelihood Functions, Single Nucleotide, Middle Aged, Psychiatry and Mental health, educational attainment, depression, Major depressive disorder, Educational Status, Regression Analysis, Female, Psychology, Adult, Estonia, medicine.medical_specialty, Biochemistry & Molecular Biology, Aged, Depressive Disorder, Major/epidemiology, Depressive Disorder, Major/genetics, Depressive Disorder, Major/psychology, Estonia/epidemiology, Gene-Environment Interaction, Genetic Association Studies, Genotype, Humans, Netherlands/epidemiology, Polymorphism, Single Nucleotide/genetics, Psychiatric Status Rating Scales, Concordance, Population, SNP, Single-nucleotide polymorphism, Genetic correlation, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Article, Cellular and Molecular Neuroscience, mental disorders, medicine, Polymorphism, education, Molecular Biology, Depressive Disorder, Depressive Disorder, Major, major depressive disorder, ta1184, Neurosciences, Major, Odds ratio, medicine.disease, ta3124, Neurosciences & Neurology, polymorphisms, Demography
Abstract: An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on similar to 120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status. Refereed/Peer-reviewed
Published: 2015
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13. Multiethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI

Author: Susan H. Blanton, Ashley Beecham, Pamela J. Schreiner, Ralph L. Sacco, Stéphanie Debette, Ben A. Oostra, Marian Beekman, M. Arfan Ikram, Edith Hofer, Anna Maria Töglhofer, Alexander Teumer, Ganesh Chauhan, Clinton B. Wright, Meike W. Vernooij, Wiro J. Niessen, Aad van der Lugt, Cornelia M. van Duijn, Christophe Tzourio, Matthias Nauck, Bernard Mazoyer, Bettina von Sarnowski, Alexa S. Beiser, Susan R. Heckbert, André G. Uitterlinden, Alex P. Zijdenbos, David S. Knopman, Paul Freudenberger, Myriam Fornage, Maaike Schuur, Stephen Turner, Matthew Traylor, Qiong Yang, Fabrice Crivello, P. Eline Slagboom, Ian J. Deary, Sharon L.R. Kardia, Cora E. Lewis, Stella Trompet, Mike A. Nalls, Jennifer A. Smith, Katrin Hegenscheid, Hans J. Grabe, Lenore J. Launer, Reinhold Schmidt, Albert V. Smith, M. Kamran Ikram, Kumar B. Rajan, Mariza de Andrade, Sudha Seshadri, Lorna M. Lopez, Philip L. De Jager, Albert Hofman, Joshua C. Bis, Gerardo Heiss, Neelum T. Aggarwal, Elizabeth J. Atkinson, Carla A. Ibrahim-Verbaas, David C. Liewald, Anton J. M. de Craen, Jing Wang, David J. Stott, Sandra Barral, Adam M. Brickman, Mohamad Habes, Eric Boerwinkle, Katharina Wittfeld, Jerome I. Rotter, Saima Hilal, R. Nick Bryan, Charles C. DeCarli, Mark A. van Buchem, Mitchell S.V. Elkind, Rebecca F. Gottesman, Christiane Wolf, Vincent Chouraki, Jeroen van der Grond, Jiemin Liao, Joris Deelen, Stephen Sidney, Kenneth Rice, Vilmundur Guðnason, Hieab H.H. Adams, Benjamin F.J. Verhaaren, Tien Yin Wong, Oliver Martinez, Denis A. Evans, Helena Schmidt, W. T. Longstreth, J. Wouter Jukema, Richard Mayeux, Joanna M. Wardlaw, Thomas H. Mosley, Michelle Luciano, Sigurdur Sigurdsson, Carole Dufouil, Christopher Chen, Philippe Amouyel, Wei Zhao, John C. van Swieten, Bruce M. Psaty, Hae-Won Uh, B. Gwen Windham, Erasmus University Medical Center [Rotterdam] (Erasmus MC), INSERM U897, University of Bordeaux, France, University of Washington [Seattle], University of Michigan [Ann Arbor], University of Michigan System, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), John P. Hussman Institute for Human Genomics, University of Miami Leonard M. Miller School of Medicine (UMMSM), Rush University Medical Center [Chicago], University of Edinburgh, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands, Depts of Radiology, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Department of Materials Science and Metallurgy [Cambridge University] (DMSM), University of Cambridge [UK] (CAM), JRC Institute for Transuranium Elements [Karlsruhe] (ITU ), European Commission - Joint Research Centre [Karlsruhe] (JRC), Greifswald University Hospital, Division of Biomedical Statistics and Informatics, Mayo Clinic, Division of Biomedical Statistics and Informatics, Mayo Clinic, Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Genetics, The University of Texas Health Science Center at Houston (UTHealth), Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University [New York], Perelman School of Medicine, University of Pennsylvania, INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, Systèmes et Applications des Technologies de l'Information et de l'Energie (SATIE), École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-École normale supérieure - Rennes (ENS Rennes)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE), Department of neurology, Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Dept of Psychology, Molecular Epidemiology, Harvard Medical School [Boston] (HMS), Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), 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], Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Columbia Mailman School of Public Health, Laboratoire pharmaceutique Lilly France [Neuilly-sur-Seine], Institute of Molecular Biology & Biochemistry, Johns Hopkins University School of Medicine [Baltimore], Faculty of Medicine, University of Iceland [Reykjavik], The Icelandic Heart Association, Kopavogur, Iceland, Institutes for Community Medicine, Department of Epidemiology, University of Washington, Group Health Research Institute, Group Health Cooperative, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), National University of Singapore (NUS), Université Grenoble Alpes - UFR Sciences de l'Homme et de la Société (UGA UFR SHS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes - UFR Langage, lettres et arts du spectacle, information et communication - Dpt Sciences de l'information et de la communication (UGA UFR LLASIC SIC), Mayo Clinic [Rochester], Academic Unit of Inflammation and Tumour Targeting, Dept. of Oncology, University of Sheffield Medical School, East China University of Science and Technology, Medstar Research Institute, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Bioinformatics, GlaxoSmithKline, National Institutes of Health [Bethesda] (NIH), Institute of Clinical Chemistry and Laboratory Medicine, Universität Greifswald - University of Greifswald, Delft University of Technology (TU Delft), Cardiovascular Health Research Unit, University of Washington, Department of Medicine, University of Washington, Department of Health Services, University of Washington, Department of Biostatistics, University of Washington, Cedars-Sinai Medical Center, Dept of Neurology, Univ Medicine of Greifswald, Germany, Department of Physics [Stockholm], Stockholm University, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Kaiser Permanente, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Department of Medical Biochemistry and Microbiology, Uppsala University, Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, King‘s College London, Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria, Research Centre for Stroke & Dementia, St George 's Univ of London, Interuniversity Cardiology Institute Netherlands, SAC, Bush Estate, School Medicine, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Singapore Eye Research Institute, Singapore National Eye Centre, University of Oslo (UiO), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ninewells Hospital and Medical School, Biomedical Research Centre, University of Dundee, Dundee Technopole, CXR Biosciences Ltd, Department of Atmospheric, Oceanic, and Space Sciences [Ann Arbor] (AOSS), University of Michigan System-University of Michigan System, University of Miami [Coral Gables], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biospective [Montréal], Dept of Epidemiology & Public Health Sciences, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Mississippi Medical Center (UMMC), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Austrian Institute of Technology [Vienna] (AIT), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Human Genetics Center, University of Pennsylvania [Philadelphia], Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Memory Aging & Cognition Centre, National Univ of Singapore, Singapore, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Dept of Ophthalmology, National Univ of Singapore & National Univ Health System, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), University of California-University of California, Radboud university [Nijmegen], Epidemiology, Radiology & Nuclear Medicine, General Practice, Neurology, Medical Informatics, Clinical Genetics, Internal Medicine, Human genetics, NCA - neurodegeneration, Hal, GIN, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and HESAM Université (HESAM)-HESAM Université (HESAM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, Male, single nucleotide, Pathology, Genome-wide association study, leukoencephalopathies, polymorphisms, single nucleotide, Chromosomes, Human, Genetics (clinical), Aged, 80 and over, education.field_of_study, Continental Population Groups, cerebrovascular disorders, Middle Aged, White Matter, 3. Good health, Stroke, genetics [Stroke], Female, cerebral small vessel diseases, Alzheimer's disease, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, hypertension, Population, genetics [Chromosomes, Human], Article, Meta-Analysis as Topic, Internal medicine, Genetics, medicine, Dementia, Humans, ddc:610, 1000 Genomes Project, education, Genetic association, Aged, Intracerebral hemorrhage, genome-wide association study, Models, Genetic, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Racial Groups, medicine.disease, ethnology [Stroke], Hyperintensity, Genetic Loci, pathology [Stroke], business, polymorphisms, Genome-Wide Association Study
Abstract: Background— The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. Methods and Results— We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 ( P =2.7×10 −19 ) and identified novel loci on chr10q24 ( P =1.6×10 −9 ) and chr2p21 ( P =4.4×10 −8 ). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 ( P =2.0×10 −8 ) and chr2p16 ( P =1.5×10 −8 ). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). Conclusions— We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.
Published: 2015
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14. Predicting stroke through genetic risk functions the CHARGE risk score project

Author: João D. Fontes, James B. Meigs, Seung Hoan Choi, M. Arfan Ikram, W. T. Longstreth, Kent D. Taylor, Aaron R. Folsom, Caroline S. Fox, Myriam Fornage, Helena Schmidt, Najaf Amin, Martin Dichgans, Lenore J. Launer, Thomas H. Mosley, Cornelia M. van Duijn, Christopher J. O'Donnell, Renske G. Wieberdink, Charles DeCarli, Alexa S. Beiser, Rebecca F. Gottesman, Eric Boerwinkle, Mike A. Nalls, Philip A. Wolf, Kenneth Rice, Jerome I. Rotter, Susan R. Heckbert, Sekar Kathiresan, Sudha Seshadri, Peter J. Koudstaal, Eyal Shahar, Madhu Rao, Luting Xue, Thomas Lumley, Abbas Dehghan, Albert Hofman, André G. Uitterlinden, Georg Ehret, Wayne D. Rosamond, Rainer Malik, Carla A. Ibrahim-Verbaas, Jari Lahti, Joshua C. Bis, Stéphanie Debette, Anita L. DeStefano, Bruce M. Psaty, Neurology, Epidemiology, Internal Medicine, and Radiology & Nuclear Medicine
Subjects: Male, Aging, Cardiorespiratory Medicine and Haematology, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, Risk Factors, Epidemiology, 80 and over, 10. No inequality, Stroke, ddc:616, Aged, 80 and over, Framingham Risk Score, Age Factors, Aged, Area Under Curve, Case-Control Studies, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Middle Aged, Polymorphism, Single Nucleotide/genetics, ROC Curve, Regression Analysis, Sex Factors, Stroke/epidemiology, Stroke/genetics, Single Nucleotide, stroke, Stroke/epidemiology/genetics, Cohort, Patient Safety, Cardiology and Cardiovascular Medicine, Cohort study, medicine.medical_specialty, genetic epidemiology, Clinical Sciences, and over, Polymorphism, Single Nucleotide, Article, White People, 03 medical and health sciences, Internal medicine, Genetics, medicine, cardiovascular diseases, Polymorphism, Advanced and Specialized Nursing, Neurology & Neurosurgery, Whites, Proportional hazards model, business.industry, Prevention, fungi, Neurosciences, Case-control study, medicine.disease, Brain Disorders, Genetic epidemiology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background and Purpose— Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. Methods— The study includes 4 population-based cohorts with 2047 first incident strokes from 22 720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case–control study of ischemic stroke. Results— In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P =2.3×10 −6 ; ischemic stroke: Δjoint area under the curve=0.021, P =3.7×10 −7 ), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index ( P −4 ). Conclusions— The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.
Published: 2014
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15. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

Author: Magnus Johannesson, André G. Uitterlinden, Cornelius A. Rietveld, Nicholas J. Timpson, Sarah E. Medland, Tõnu Esko, Beben Benyamin, Ian J. Deary, Sven J. van der Lee, Christiaan de Leeuw, Nicholas G. Martin, Matt McGue, Cornelia M. van Duijn, David C. Liewald, Patrick Turley, Nancy L. Pedersen, Paul Lichtenstein, Jaime Derringer, Frank C. Verhulst, James J. Lee, Carla A. Ibrahim-Verbaas, Dalton Conley, Philipp Koellinger, John M. Starr, Tune H. Pers, Christopher F. Chabris, David Cesarini, David Laibson, Edward L. Glaeser, Najaf Amin, Olga Rostapshova, Maciej Trzaskowski, Juha Karjalainen, Mary E. Ward, Caroline Hayward, Valur Emilsson, Patrik K. E. Magnusson, Henning Tiemeier, Daniel J. Benjamin, Robert Plomin, David J. Porteous, George Davey Smith, Michael B. Miller, Margaret J. Wright, Fernando Rivadeneira, Vincent W. V. Jaddoe, Anna A. E. Vinkhuyzen, William G. Iacono, Lude Franke, Peter M. Visscher, Rudolf S N Fehrmann, Gail Davies, Andrew D. Johnson, Steven Pinker, Riccardo E. Marioni, Blair H. Smith, George McMahon, Danielle Posthuma, Narelle K. Hansell, Human genetics, NCA - Brain mechanisms in health and disease, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Functional Genomics, Complex Trait Genetics, Tinbergen Institute, Amsterdam Neuroscience - Complex Trait Genetics, Rietveld, Cornelius A, Esko, Tõnu, Davies, Gail, Pers, Tune H, Benyamin, Beben, Koellinger, Philipp D, 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), Stem Cell Aging Leukemia and Lymphoma (SALL), Entrepreneurship & Innovation (ABS, FEB), Epidemiology, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, and Internal Medicine
Subjects: Male, Multifactorial Inheritance, Cell Adhesion Molecules, Neuronal, LOCI, Social Sciences, Single-nucleotide polymorphism, Genome-wide association study, INTELLIGENCE, Nerve Tissue Proteins, Biology, Polymorphism, Single Nucleotide, Synaptic Transmission, Corrections, Cognition, Memory, medicine, ACADEMIC-ACHIEVEMENT, Dementia, GWAS, Humans, Learning, Effects of sleep deprivation on cognitive performance, GENOME-WIDE ASSOCIATION, Neural Cell Adhesion Molecules, Genetics, Multidisciplinary, Neuronal Plasticity, proxy-phenotype method, Memoria, COMPONENTS, Calcium-Binding Proteins, medicine.disease, Multiple comparisons problem, Octamer Transcription Factors, Female, SDG 4 - Quality Education
Abstract: We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory. Refereed/Peer-reviewed
Published: 2014
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16. P1–065: Genetic variants associated with incidence of late‐onset Alzheimer's disease in Caucasians

Author: Mohammad Arfan Ikram, Carla A. Ibrahim-Verbaas, Vincent Chouraki, Annette L. Fitzpatrick, Jean-Charles Lambert, Céline Bellenguez, Lei Yu, Philippe Amouyel, Sudha Seshadri, Richard Mayeux, Anita L. DeStefano, Lenore J. Launer, Shubhabrata Mukherjee, David A. Bennett, Cornelia M. van Duijn, Christiane Reitz, Renée F.A.G. de Bruijn, Eric B. Larson, Seung Hoan Choi, Paul K. Crane, Oscar L. Lopez, Joshua C. Bis, Benjamin Grenier-Bolay, and Badri N. Vardarajan
Subjects: Epidemiology, business.industry, Health Policy, Incidence (epidemiology), Genetic variants, Late onset, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Immunology, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2013
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17. P4–003: A genomewide association meta‐analysis of plasma beta‐amyloid peptide concentrations in the elderly

Author: Jean-Charles Lambert, Jean-François Dartigues, Florie Demiautte, Benjamin Grenier-Boley, Christiane Reitz, Cornelia M. van Duijn, Albert Hofman, Susanna Schraen-Maschke, Nicole Schupf, Luc Buée, Renée F.A.G. de Bruijn, Claudine Berr, Christophe Tzourio, Vincent Chouraki, Julien Chapuis, Mark Lathrop, Philippe Amouyel, Carla A. Ibrahim-Verbaas, Mohammad Arfan Ikram, Annick Alpérovitch, André G. Uitterlinden, Robert S. Rogers, and Richard Mayeux
Subjects: chemistry.chemical_classification, medicine.medical_specialty, Amyloid, Epidemiology, Chemistry, Health Policy, Peptide, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Endocrinology, Developmental Neuroscience, Internal medicine, Meta-analysis, Genomewide association, medicine, Neurology (clinical), Geriatrics and Gerontology, Beta (finance)
Published: 2013
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18. Variant of TREM2 Associated with the Risk of Alzheimer's Disease

Author: Thorlakur Jonsson, Albert Hofman, Johanna Huttenlocher, Harald Hampel, James J. Lah, Augustine Kong, Knut Engedal, Ingileif Jonsdottir, Cornelia M. van Duijn, Carla A. Ibrahim-Verbaas, Jon Snaedal, M. Arfan Ikram, Ingun Ulstein, Sigurbjorn Bjornsson, Unnur Thorsteinsdottir, Stacy Steinberg, Kari Stefansson, Dan Rujescu, Allan I. Levey, Ina Giegling, Palmi V. Jonsson, Srdjan Djurovic, Hreinn Stefansson, Ole A. Andreassen, Neurology, Epidemiology, Radiology & Nuclear Medicine, and Decode, Landspitali University Hospital, Reykjavik, Iceland
Subjects: Apolipoprotein E, Oncology, medicine.medical_specialty, Heterozygote, Genotyping Techniques, SORL1, Population, Apolipoprotein E4, Iceland, Mutation, Missense, Bioinformatics, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Cognition, Alzheimer Disease, Risk Factors, Internal medicine, medicine, Humans, Receptors, Immunologic, education, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, education.field_of_study, Membrane Glycoproteins, TREM2, business.industry, Case-control study, Genetic Variation, General Medicine, Odds ratio, Sequence Analysis, DNA, medicine.disease, 3. Good health, Case-Control Studies, Alzheimer's disease, business, 030217 neurology & neurosurgery, Common disease-common variant
Abstract: To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. BACKGROUND: Sequence variants, including the ε4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer's disease. Few rare variants affecting the risk of late-onset Alzheimer's disease have been found. METHODS: We obtained the genome sequences of 2261 Icelanders and identified sequence variants that were likely to affect protein function. We imputed these variants into the genomes of patients with Alzheimer's disease and control participants and then tested for an association with Alzheimer's disease. We performed replication tests using case-control series from the United States, Norway, The Netherlands, and Germany. We also tested for a genetic association with cognitive function in a population of unaffected elderly persons. RESULTS: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42×10(-10)). The mutation had a frequency of 0.46% in controls 85 years of age or older. We observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P=2.1×10(-12) in combined discovery and replication samples). We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers (P=0.003). CONCLUSIONS: Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes. (Funded by the National Institute on Aging and others.). Research Council of Norway National Institute on Aging P50-AG025688 U01AG006781 South-Eastern Norway Health Authority National Institutes of Health U01HG004438 National Human Genome Research Institute U01HG004610 eMERGE Administrative Coordinating Center U01HG004603 National Center for Biotechnology Information Erasmus Medical Center Erasmus University, Rotterdam Netherlands Organization for Health Research and Development Research Institute for Diseases in the Elderly Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports Municipality of Rotterdam Research Institute for Diseases in the Elderly 014-93-015 Stichting Alzheimer Onder-zoek Hersenstichting Nederland Netherlands Genomics Initiative-Netherlands Organization for Scientific Research (Center for Medical Systems Biology and the Netherlands Consortium for Healthy Aging) info:eu-repo/grantAgreement/EC/FP7/201413
Published: 2013

19. GWAS of 126559 Individuals Identifies Genetic Variants Associated with Educational Attainment

Author: Maria Dimitriou, Klaus Berger, Jian Yang, Nicholas J. Timpson, George Dedoussis, Magnus Johannesson, Igor Rudan, Marisa Loitfelder, Kurt Lohman, Jürgen Wellmann, Osorio Meirelles, Johan G. Eriksson, Cornelia M. van Duijn, Francesco Cucca, Anu Realo, Gérard Waeber, David R. Van Wagoner, Samuli Ripatti, Alan F. Wright, George McMahon, Elizabeth G. Holliday, Lili Milani, Ute Bültmann, Olli T. Raitakari, Behrooz Z. Alizadeh, Reinhold Schmidt, Matthew Kowgier, André G. Uitterlinden, Sutapa Mukherjee, William G. Iacono, Judith M. Vonk, Lude Franke, John M. Starr, Antonio Terracciano, Rudolf Ferhmann, Pamela A. F. Madden, Marika Kaakinen, Helena Schmidt, Dorret I. Boomsma, Harry Campbell, Konstantin Shakhbazov, Lei Yu, Albert Hofman, Tõnu Esko, Cornelius A. Rietveld, Albert V. Smith, Arpana Agrawal, Wouter J. Peyrot, Stefania Bandinelli, David M. Evans, Nicolas W. Martin, Martin F. Elderson, Melissa E. Garcia, Danielle Posthuma, Ozren Polasek, Panos Deloukas, Pedro Marques Vidal, Sang Hong Lee, James F. Wilson, Robert F. Krueger, Paul Lichtenstein, Jan-Emmanuel De Neve, Fernando Rivadeneira, Laura J. Bierut, Sebastian E. Baumeister, Lawrence F. Bielak, Peter M. Visscher, Philipp Koellinger, Thais S. Rizzi, Rodney J. Scott, Mika Kähönen, Marco Masala, Debbie A Lawlor, Yongmei Liu, Ben A. Oostra, Jaime Derringer, Zoltán Kutalik, Carla A. Ibrahim-Verbaas, Toshiko Tanaka, Håkon K. Gjessing, Jae Hoon Sul, Marjo-Riitta Järvelin, Krista Fischer, Erik Ingelsson, David R. Weir, Kati Kristiansson, Thomas Illig, Jorma Viikari, George Davey-Smith, Antti-Pekka Sarin, Matt McGue, Ida Surakka, Andreas Mielck, Ivana Kolcic, Astanand Jugessur, Aldo Rustichini, Sarah E. Medland, Ronny Myhre, Veikko Salomaa, Mina K. Chung, H.-Erich Wichmann, Lynn Cherkas, Peter Lichtner, Michael B. Miller, Peter Vollenweider, Jüri Allik, Henning Tiemeier, Grant W. Montgomery, Eva Reinmaa, Dalton Conley, Adriaan Hofman, Patricia A. Peyser, David Schlessinger, Martin Preisig, Jessica D. Faul, Patrik K. E. Magnusson, David A. Bennett, Erkki Vartiainen, David Laibson, François Bastardot, Niina Eklund, Wolfgang Hoffmann, Terho Lehtimäki, Nicholas D. Hastie, John P. Rice, Rolf Holle, Antti Latvala, Guoný Eiríksdóttir, Luigi Ferrucci, Jennifer A. Smith, Christian Gieger, Veronique Vitart, Gail Davies, Sara Hägg, Juha Karjalainen, Matthijs J. H. M. van der Loos, Bo Jacobsson, Lydia Quaye, John Barnard, Beate St Pourcain, Jouke-Jan Hottenga, Daniel S. Evans, Jonathan P. Beauchamp, Tamara B. Harris, Ian J. Deary, Jari Lahti, Peng Lin, Markus Perola, Henry Völzke, Lenore J. Launer, David C. Liewald, Brenda W.J.H. Penninx, David Cesarini, Najaf Amin, Dale R. Nyholt, Roy Thurik, Aarno Palotie, Patrick J. F. Groenen, Elisabeth Widen, Caroline Hayward, Penelope A. Lind, Susan M. Ring, Lyle J. Palmer, Alexander Teumer, Kelly S. Benke, Christopher Oldmeadow, Katja Petrovic, Gonneke Willemsen, Andrew C. Heath, Harold Snieder, Jaakko Kaprio, Marja-Liisa Nuotio, Frank J. A. van Rooij, Robert M. Kirkpatrick, Nicholas G. Martin, Tomi E. Mäkinen, Michelle N. Meyer, Katri Räikkönen, Harm-Jan Westra, Daniel J. Benjamin, Jeffrey A. Boatman, Henrik Grönberg, Eva Albrecht, Sharon L.R. Kardia, Peter K. Joshi, Philip L. De Jager, Mariza de Andrade, Patricia A. Boyle, Jennifer R. Harris, Vilmundur Guonason, Christiaan de Leeuw, Juliette Harris, Dena G. Hernandez, Jingmei Li, Per Hall, Wei Zhao, Abdel Abdellaoui, Andres Metspalu, Christina Holzapfel, Stavroula Kanoni, Christopher F. Chabris, John Attia, Rauli Svento, Erasmus School of Economics, Epidemiology, Surgery, Neurology, Applied Economics, Research Methods and Techniques, Clinical Genetics, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Econometrics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Biological Psychology, Functional Genomics, Management and Organisation, Tinbergen Institute, Amsterdam Neuroscience - Complex Trait Genetics, Rietveld, Cornelius A, Medland, Sarah E, Derringer, Jaime, Yang, Jian, Lee, Sang Hong, Koellinger, Philipp D, LifeLines Cohort Study, ABS Other Research (FEB), Reproductive Origins of Adult Health and Disease (ROAHD), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Public Health Research (PHR), Teaching and Teacher Education, Groningen Research Institute for Asthma and COPD (GRIAC), Stem Cell Aging Leukemia and Lymphoma (SALL), Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
Subjects: Netherlands Twin Register (NTR), Male, medicine.medical_specialty, Multifactorial Inheritance, Endophenotypes, social-science genetics, LOCI, SNP, Single-nucleotide polymorphism, Genome-wide association study, Biology, PREFERENCES, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Cognition, Polymorphism (computer science), medicine, GWAS, Humans, Allele, Polymorphism, education, gene, attainment, 030304 developmental biology, Genetics, 0303 health sciences, ENVIRONMENT, genome-wide association study, Multidisciplinary, Data Science, Replicate, Single Nucleotide, single-nucleotide polymorphism, linear polygenic score, ta3121, Educational attainment, Multidisciplinary Sciences, Educational Status, Female, Genetic Loci, Genome-Wide Association Study, educational attainment, Endophenotype, Medical genetics, 030217 neurology & neurosurgery
Abstract: Genetic College Many genomic elements in humans are associated with behavior, including educational attainment. In a genome-wide association study including more than 100,000 samples, Rietveld et al. (p. 1467 , published online 30 May; see the Perspective by Flint and Munafò ) looked for genes related to educational attainment in Caucasians. Small genetic effects at three loci appeared to impact educational attainment.
Published: 2013
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20. P2‐035: Phosphosphingolipid levels are associated with cognitive function and level of education in healthy subjects

Author: Najaf Amin, John C. van Swieten, Carla A. Ibrahim-Verbaas, Aaron Isaacs, Cornelia M. van Duijn, Ben A. Oostra, and Ayse Demirkan
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Healthy subjects, Cognition, Audiology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2012
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20 results on '"Carla A Ibrahim-Verbaas"'

1. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

2. Human prion diseases in the Netherlands (1998-2009): clinical, genetic and molecular aspects.

3. Genome-wide association study identifies risk variants for sporadic Creutzfeldt-Jakob disease in STX6 and GAL3ST1

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

5. Convergent genetic and expression data implicate immunity in Alzheimer's disease

6. A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

7. Polygenic scores associated with educational attainment in adults predict educational achievement and ADHD symptoms in children

8. The sex-specific associations of the aromatase gene with Alzheimer's disease and its interaction with IL10 in the Epistasis Project

9. Intensity of human prion disease surveillance predicts observed disease incidence

10. Evaluation of a Genetic Risk Score to Improve Risk Prediction for Alzheimer's Disease

11. Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease

12. The association between lower educational attainment and depression owing to shared genetic effects?: Results in ~25,000 subjects

13. Multiethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI

14. Predicting stroke through genetic risk functions the CHARGE risk score project

15. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

16. P1–065: Genetic variants associated with incidence of late‐onset Alzheimer's disease in Caucasians

17. P4–003: A genomewide association meta‐analysis of plasma beta‐amyloid peptide concentrations in the elderly

18. Variant of TREM2 Associated with the Risk of Alzheimer's Disease

19. GWAS of 126559 Individuals Identifies Genetic Variants Associated with Educational Attainment

20. P2‐035: Phosphosphingolipid levels are associated with cognitive function and level of education in healthy subjects

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