Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population.
Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD. We identified 2 heterozygous missense variants in 2 unrelated PD cases and not in our control database (p.Y106H and p.I162V), and a heterozygous missense variant in 2 PD cases from the same family (p.A163T). However, data presented herein is not sufficient to support the role of any of these variants in PD pathology. A series of unified sequence kernel association tests also failed to show a cumulative effect of rare variation in this gene on the risk of PD in the general Caucasian population. Further evaluation of genetic data from different populations is needed to understand the genetic role of TMEM230 in PD etiology.
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Anamika
A
Giri
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Kin Y
KY
Mok
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Department of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands.
Iris
I
Jansen
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
Manu
M
Sharma
Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
Christelle
C
Tesson
Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
Graziella
G
Mangone
Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
Suzanne
S
Lesage
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
José M
JM
Bras
Departments of Neurology and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Joshua M
JM
Shulman
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Una-Marie
UM
Sheerin
Movement Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
Mónica
M
Díez-Fairen
Movement Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
Pau
P
Pastor
Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
María José
MJ
Martí
Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
Mario
M
Ezquerra
Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
Eduardo
E
Tolosa
Department of Neurosciences, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
Leonor
L
Correia-Guedes
Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
Joaquim
J
Ferreira
Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
Najaf
N
Amin
Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
Cornelia M
CM
van Duijn
Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Ageing (NCHA), Rotterdam, the Netherlands.
Jeroen
J
van Rooij
Department of Neurosciences, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal; Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Ageing (NCHA), Rotterdam, the Netherlands.
André G
AG
Uitterlinden
Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Ageing (NCHA), Rotterdam, the Netherlands.
Robert
R
Kraaij
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
Michael
M
Nalls
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. Electronic address: javier.simon-sanchez@dzne.de.
Javier
J
Simón-Sánchez
D030541:Databases, Genetic; D059472:Exome / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D012306:Risk; D017421:Sequence Analysis; D044465:White People / Q000235:genetics
D008565:Membrane Proteins; C000622360:TMEM230 protein, human
IPDGC; Mutation screening; Parkinson's disease; Rotterdam Study Exome Sequencing Database; SKAT-O; TMEM230