Donders Institute for Brain, Cognition and Behaviour
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Theme 3: Plasticity and Memory

Genetics of Brain Function and (Psychiatric) Malfunction

Donders Institute for Brain, Cognition and BehaviourMost psychiatric disorders are highly heritable, but due to their multifactorial origins it has been very hard to identify the individual genes involved. In my group, we use different approaches to identify risk genes for disease; in addition to using the classic clinical phenotypes we make use of intermediate phenotypes. These phenotypes are based on neuropsychological performance or neuroimaging.

In addition to studying patients, much of our research is currently devoted to cognition in healthy volunteers. For this, we have founded and lead the Cognomics Initiative, in which we try to understand how genetic variation influences behaviour via its effect on brain structure and function. A major Cognomics project is the Brain Imaging Genetics (BIG) study. For BIG, we have collected structural brain (MRI) scans and DNA of >2500 young, healthy individuals. In 1400 of those, we have performed a genome-wide association study to identify new genes for brain structure - and related brain function. For this work, we also became one of the founding members of the international ENIGMA (Enabling NeuroImaging Genetics through Meta-Analysis) consortium, in which we participate in the central support group.

Besides gene-finding approaches, we also try to understand, how known genetic risk factors for a disorder exert their effects, by mapping gene-to-disease pathways in the brain. This is done using brain imaging, but we also use the fruit fly Drosophila melanogaster to study gene effects at the cellular level as well as on behaviour. We work in close collaboration with the local departments of Psychiatry, Cognitive Neuroscience, the Donders Centre for Cognitive Neuroimaging and Karakter Child and Adolescent Psychiatric Centre.

Contact
Name: Barbara Franke
Telephone: 024-3614017
Email:

b.franke@donders.ru.nl
Barbara.Franke@radboudumc.nl

Visiting address:

Department of Human Genetics Radboud University Nijmegen Medical Centre
route 855 
Geert Grooteplein Zuid 10
6525 GA Nijmegen
The Netherlands

Postal address: Department of Human Genetics Radboud University Nijmegen Medical Centre
P.O. Box 9101 / 855
6500 HB Nijmegen
The Netherlands
Projects
  • Founder and coordinator of the International Multicentre persistent ADHD collaboration (IMpACT). IMpACT currently includes 5 research groups from Europe, 2 from the US and 1 from Brazil and coordinates the largest clinical ADHD sample for genetic research, worldwide (>3500 cases, >4000 controls)
  • Founding member and member of the central support group of the ENIGMA (Enabling NeuroImaging Genetics through Meta-Analysis) consortium (http://enigma.loni.ucla.edu/), which performs large meta-analyses of brain structure and function
  • Co-PI of the International Multicentre ADHD Genetics (IMAGE) study, which has collected over 1400 families with at least 1 affected child
  • Co-PI of the Dutch NeuroIMAGE study (http://www.neuroimage.nl/), in which the 400 Dutch IMAGE families are investigated longitudinally in a second and third wave, using clinical, neuroimaging and neuropsychological assessments (probands + sibs + controls + parents)
  • Work package leader of the Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes (TACTICS) Project
  • Participant in the Autism Genome Project (AGP)
  • Active member of the Psychiatric Genomics Consortium (PGC; https://pgc.unc.edu/), which performs large meta-analyses of genome-wide studies of common and rare genetic variants in psychiatric disorders
  • Member of the international ADHD Molecular Genetics Network
Key grants and prizes
  • Brain & Cognition Excellence Grant (2010): From genetic pathways to cognition in ADHD: a question of the right connections?
  • EU FP7 Health Grant (2012): Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes – TACTICS; we lead WP5: Genotyping and Phenotyping
  • Aspasia Award of the Netherlands Organization for Scientific Research (2012)
  • Radboud University Nijmegen Hermesdorf Prize International for media coverage of research in the year 2012 (2013)
  • Vici Grant of the Netherlands Organization for Scientific Research (2013): Networking through ADHD Biology
Key publications
  • Franke B, Faraone SV, Asherson P, Buitelaar J, Bau CHD, Ramos-Quiroga JA, Mick E, Grevet EH, Johansson S, Haavik J, Lesch KP, Cormand B, Reif A, on behalf of the International Multicentre persistent ADHD CollaboraTion, IMpACT (2012). The genetics of attention deficit/hyperactivity disorder (ADHD) in adults, a review. Mol Psychiatry, invited review, 17 (10), 960-987 [Epub Nov 22 2011]
  • Stein JL*, Medland SE*, Arias Vasquez A*, Hibar DP*, Senstad RE, Winkler AM, Toro R, Appel K, Bartecek R, Bergmann Ø, Bernard M, Brown AA, Cannon DM, Chakravarty M, Christoforou A, Domin M, Grimm O, Hollinshead M, Holmes AJ, Homuth G, Hottenga JJ, Langan C, Lopez LM, Hansell NK, Hwang KS, Kim S, Laje G, Lee PH, Liu X, Loth E, Lourdusamy A, Muñoz Maniega S, Mattingsdal M, Mohnke S, Nho K, Nugent AC, O’Brien C, Papmeyer M, Pütz B, Ramasamy A, Rijpkema M, Risacher SL, Rose EJ, Ryten M, Shen L, Sprooten E, Strengman E, Teumer A, Trabzuni A, van Eijk K, van Erp TGM, van Tol MJ, Wittfeld K, Wolf C, Woudstra S, Aleman A, Alhusaini S, Almasy L, Binder EB, Brohawn DG, Cantor RM, Carless MA, Corvin A, Czisch M, Curran JE, Davies G, Delanty N, Depondt C, Duggirala R, Dyer TD, Erk S, Fagerness J, Fox PT, Freimer NB, Gill M, Göring HHH, Hoehn D, Holsboer F, Hoogman M, Johnson MP, Kasperaviciute D, Kent, Jr., JW, Kochunov P, Lancaster JL, Lawrie SM, Liewald DC, Mandl R, Matarin M, Mattheisen M, Meisenzahl E, Melle I, Moses EK, Mühleisen TW, Nauck M, Nöthen MM, Olvera RL, Pandolfo M, Pike GB, Puls R, Reinvang I, Rentería ME, Rietschel M, Roffman JL, Royle NA, Rujescu D, Savitz J, Schnack HG, Schnell K, Seiferth N, Smith C, Steen VM, Valdés Hernández MC, Van den Heuvel M, van der Wee NJ, Van Haren NEM, Veltman JA, Völzke H, Walker R, Agartz I, Boomsma DI, Cavalleri GL, Dale AM, Djurovic S, Drevets WC, Hagoort P, Hall J, Heinz A, Jack Jr CR, Foroud TM, Le Hellard S, Macciardi F, Montgomery GW, Poline JB, Porteous DJ, Sisodiya SM, Starr JM, Sussmann J, Toga AW, Veltman DJ, Walter H, Weiner MW, the Alzheimer’s Disease Neuroimaging Initiative, IMAGEN Consortium, Saguenay Youth Study Group, Bis JC, Ikram MA, Smith AV, Tzourio C, Vernooij MW, Launer LJ, DeCarli C, Seshadri S, for the CHARGE Consortium, Andreassen OA, Apostolova LG, Bastin ME, Blangero J, Brunner HG, Buckner RL, Cichon S, Coppola G, de Zubicaray GI, Deary IJ, Donohoe G, de Geus EJC, Espeseth T, Fernández G, Glahn DC, Grabe HJ, Hardy J, Jenkinson M, Kahn RS, McDonald C, McIntosh AM, McMahon FC, McMahon KL, Meyer-Lindenberg A, Morris DW, Müller-Myhsok B, Nichols TE, Ophoff RA, Paus T, Pausova Z, Penninx BW, Hulshoff Pol HE, Potkin SG, Sämann PG, Saykin AJ, Schumann G, Smoller JW, Wardlaw JW, Weale ME, Martin NG#, Franke B#, Wright MJ#, Thompson PM#, for the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium (2012). Common genetic polymorphisms are associated with human hippocampal and intracranial volumes. Nature Genetics 44 (5), 5552-5561 [Epub 2012 April 15] (*equal contribution; #shared final responsibility)
  • Bralten J, Arias-Vásquez A, Makkinje R, Veltman JA, Brunner HG, Fernández G, Rijpkema M, Franke B (2011). The Alzheimer’s gene SORL1 is associated with hippocampal volume in young healthy adults. Am J Psychiatry, 168 (10), 1083-1089 [Epub 2011 Jul 5]
  • Hoogman M, Aarts E, Zwiers M, Slaats-Willemse D, Naber M, Cools R, Kan C, Buitelaar JK, Franke B (2011). Reward-related activity in the striatum and impulsivity vary with Nitric Oxide Synthase genotype in Attention Deficit/Hyperactivity Disorder patients and healthy subjects. Am J Psychiatry, 168 (10), 1099-1106 [Epub 2011 Jul 1]
  • Poelmans G, Pauls D, Buitelaar JK, Franke B (2011). Integrated genome-wide association findings identify a neurodevelopmental network for attention deficit hyperactivity disorder (ADHD). Am J Psychiatry, 168 (4), 365-377 [Epub 2011 Feb 15]

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Theme 3:
Plasticity and Memory

Donders
Research Group
Genetics of Brain Function and (Psychiatric) Malfunction


Principal Investigator
Prof. dr. B. Franke

Group members

Postdocs
Janita Bralten
Jordi Corominas Galbany
Martine Hoogman
Geert Poelmans
Elena Shumskaya
Monique van der Voet

PhDs
Marjolein van Donkelaar
Marieke Klein
Ti Ling
Euginia Singgih
Francesco Waddington
Thomas Wolfers
Zhaomin Wu

Lab manager
Angelien Heister

Technicians
Remco Makkinje
Marlies Naber
Marina Hakobjan
Saskia van der Marel
Johanne Groothuismink

Research assistant
Janneke Dammers

Bioinformatician
Arjen Henkes