PMID- 26497834
OWN - NLM
STAT- MEDLINE
DCOM- 20160829
LR  - 20181202
IS  - 1098-2272 (Electronic)
IS  - 0741-0395 (Linking)
VI  - 39
IP  - 8
DP  - 2015 Dec
TI  - Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans 
      Using the Exome Array.
PG  - 601-8
LID - 10.1002/gepi.21933 [doi]
AB  - Genome-wide association studies (GWAS) successfully identified various 
      chromosomal regions to be associated with multiple sclerosis (MS). The primary 
      aim of this study was to replicate reported associations from GWAS using an exome 
      array in a large German study. German MS cases (n = 4,476) and German controls (n 
      = 5,714) were genotyped using the Illumina HumanExome v1-Chip. Genotype calling 
      was performed with the Illumina Genome Studio(TM) Genotyping Module, followed by 
      zCall. Single-nucleotide polymorphisms (SNPs) in seven regions outside the human 
      leukocyte antigen (HLA) region showed genome-wide significant associations with 
      MS (P values < 5 x 10(-8) ). These associations have been reported previously. In 
      addition, SNPs in three previously reported regions outside the HLA region 
      yielded P values < 10(-5) . The effect of nine SNPs in the HLA region remained (P 
      < 10(-5) ) after adjustment for other significant SNPs in the HLA region. All of 
      these findings have been reported before or are driven by known risk loci. In 
      summary, findings from previous GWAS for MS could be successfully replicated. We 
      conclude that the regions identified in previous GWAS are also associated in the 
      German population. This reassures the need for detailed investigations of the 
      functional mechanisms underlying the replicated associations.
CI  - (c) 2015 WILEY PERIODICALS, INC.
FAU - Dankowski, Theresa
AU  - Dankowski T
AD  - Institut fur Medizinische Biometrie und Statistik, Universitat zu Lubeck, 
      Universitatsklinikum Schleswig-Holstein, Campus Lubeck, Lubeck, Germany.
FAU - Buck, Dorothea
AU  - Buck D
AD  - Department of Neurology, Technische Universitat Munchen, Munich, Germany.
FAU - Andlauer, Till F M
AU  - Andlauer TF
AD  - Max-Planck-Institut fur Psychiatrie, Munich, Germany.
FAU - Antony, Gisela
AU  - Antony G
AD  - Central Information Office (CIO), Philipps University Marburg, Marburg, Germany.
FAU - Bayas, Antonios
AU  - Bayas A
AD  - Department of Neurology, Klinikum Augsburg, Augsburg, Germany.
FAU - Bechmann, Lukas
AU  - Bechmann L
AD  - Department of Neurology, University of Leipzig, Leipzig, Germany.
AD  - Institute of Medical Microbiology, Otto-von-Guericke University, Magdeburg, 
      Germany.
FAU - Berthele, Achim
AU  - Berthele A
AD  - Department of Neurology, Technische Universitat Munchen, Munich, Germany.
FAU - Bettecken, Thomas
AU  - Bettecken T
AD  - Max-Planck-Institut fur Psychiatrie, Munich, Germany.
FAU - Chan, Andrew
AU  - Chan A
AD  - Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, 
      Germany.
FAU - Franke, Andre
AU  - Franke A
AD  - Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University of 
      Kiel, Kiel, Germany.
FAU - Gold, Ralf
AU  - Gold R
AD  - Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, 
      Germany.
FAU - Graetz, Christiane
AU  - Graetz C
AD  - Department of Neurology, University Medical Center Mainz, Mainz, Germany.
FAU - Haas, Jurgen
AU  - Haas J
AD  - Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.
FAU - Hecker, Michael
AU  - Hecker M
AD  - Department of Neurology, University of Rostock, Rostock, Germany.
FAU - Herms, Stefan
AU  - Herms S
AD  - Institute of Human Genetics, University of Bonn, Bonn, Germany.
AD  - Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
AD  - Division of Medical Genetics, University Hospital, Basel, Switzerland.
AD  - Human Genetics Research Group, Department of Biomedicine, University of Basel, 
      Basel, Switzerland.
FAU - Infante-Duarte, Carmen
AU  - Infante-Duarte C
AD  - Department of Neurology, Charite University Medicine Berlin, Berlin, Germany.
FAU - Jockel, Karl-Heinz
AU  - Jockel KH
AD  - Institute of Medical Informatics, Biometry and Epidemiology, University Hospital 
      Essen, University Duisburg-Essen, Essen, Germany.
FAU - Kieseier, Bernd C
AU  - Kieseier BC
AD  - Department of Neurology, Heinrich Heine University, Dusseldorf, Germany.
FAU - Knier, Benjamin
AU  - Knier B
AD  - Department of Neurology, Technische Universitat Munchen, Munich, Germany.
FAU - Knop, Matthias
AU  - Knop M
AD  - Department of Neurology, MPI of Psychiatry, Munich, Germany.
FAU - Kumpfel, Tania
AU  - Kumpfel T
AD  - Institute of Clinical Neuroimmunology, Ludwigs-Maximilians-Universitat, Munich, 
      Germany.
FAU - Lichtner, Peter
AU  - Lichtner P
AD  - Institute of Human Genetics, Technische Universitat Munchen, Munich, Germany.
AD  - Institute of Human Genetics, Helmholtz Zentrum Munchen, German Research Center 
      for Environmental Health, Neuherberg, Germany.
FAU - Lieb, Wolfgang
AU  - Lieb W
AD  - Institute of Epidemiology and Biobank popgen, Christian-Albrechts-Universitat 
      Kiel, Kiel, Germany.
FAU - Lill, Christina M
AU  - Lill CM
AD  - Department of Neurology, University Medical Center Mainz, Mainz, Germany.
AD  - Platform for Genome Analytics, Institutes of Neurogenetics, & for Integrative and 
      Experimental Genomics, University of Lubeck, Lubeck, Germany.
FAU - Limmroth, Volker
AU  - Limmroth V
AD  - Department of Neurology, Hospital Koln-Merheim, Koln, Germany.
FAU - Linker, Ralf A
AU  - Linker RA
AD  - Department of Neurology, University Hospital Erlangen, Erlangen, Germany.
FAU - Loleit, Verena
AU  - Loleit V
AD  - Department of Neurology, Technische Universitat Munchen, Munich, Germany.
FAU - Meuth, Sven G
AU  - Meuth SG
AD  - Department fur Neurologie, Klinik fur Allgemeine Neurologie, Munster, Germany.
FAU - Moebus, Susanne
AU  - Moebus S
AD  - Institute of Medical Informatics, Biometry and Epidemiology, University Hospital 
      Essen, University Duisburg-Essen, Essen, Germany.
FAU - Muller-Myhsok, Bertram
AU  - Muller-Myhsok B
AD  - Max-Planck-Institut fur Psychiatrie, Munich, Germany.
FAU - Nischwitz, Sandra
AU  - Nischwitz S
AD  - Department of Neurology, MPI of Psychiatry, Munich, Germany.
FAU - Nothen, Markus M
AU  - Nothen MM
AD  - Institute of Human Genetics, University of Bonn, Bonn, Germany.
AD  - Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
FAU - Paul, Friedemann
AU  - Paul F
AD  - Department of Neurology, Charite University Medicine Berlin, Berlin, Germany.
AD  - NeuroCure Clinical Research Center, Experimental and Clinical Research Center, 
      Max Delbrueck Center for Molecular Medicine and, Charite Universitatsmedizin 
      Berlin, Berlin, Germany.
FAU - Putz, Michael
AU  - Putz M
AD  - Department of Neurology, Philipps-University of Marburg, Marburg, Germany.
FAU - Ruck, Tobias
AU  - Ruck T
AD  - Department fur Neurologie, Klinik fur Allgemeine Neurologie, Munster, Germany.
FAU - Salmen, Anke
AU  - Salmen A
AD  - Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, 
      Germany.
FAU - Stangel, Martin
AU  - Stangel M
AD  - Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover 
      Medical School, Hannover, Germany.
FAU - Stellmann, Jan-Patrick
AU  - Stellmann JP
AD  - Department of Neurology and, Institute of Neuroimmunology and MS (INIMS), 
      University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
FAU - Strauch, Konstantin
AU  - Strauch K
AD  - Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research 
      Center for Environmental Health, Neuherberg, Germany.
AD  - Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic 
      Epidemiology, Ludwig-Maximilians-Universitat, Munich, Germany.
FAU - Sturner, Klarissa H
AU  - Sturner KH
AD  - Department of Neurology and, Institute of Neuroimmunology and MS (INIMS), 
      University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
FAU - Tackenberg, Bjorn
AU  - Tackenberg B
AD  - Department of Neurology, Philipps-University of Marburg, Marburg, Germany.
FAU - Then Bergh, Florian
AU  - Then Bergh F
AD  - Department of Neurology and Translational Center for Regenerative Medicine, 
      University of Leipzig, Leipzig, Germany.
FAU - Tumani, Hayrettin
AU  - Tumani H
AD  - Department of Neurology, University of Ulm, Ulm, Germany.
FAU - Waldenberger, Melanie
AU  - Waldenberger M
AD  - Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen, German 
      Research Center for Environmental Health, Neuherberg, Germany.
AD  - Institute of Epidemiology II, Helmholtz Zentrum Munchen, German Research Center 
      for Environmental Health, Neuherberg, Germany.
FAU - Weber, Frank
AU  - Weber F
AD  - Department of Neurology, MPI of Psychiatry, Munich, Germany.
AD  - Neurological Clinic, Medical Park, Bad Camberg, Germany.
FAU - Wiendl, Heinz
AU  - Wiendl H
AD  - Department fur Neurologie, Klinik fur Allgemeine Neurologie, Munster, Germany.
FAU - Wildemann, Brigitte
AU  - Wildemann B
AD  - Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.
FAU - Zettl, Uwe K
AU  - Zettl UK
AD  - Department of Neurology, University of Rostock, Rostock, Germany.
FAU - Ziemann, Ulf
AU  - Ziemann U
AD  - Department of Neurology, University Hospital, Eberhard-Karls-Universitat 
      Tubingen, Tubingen, Germany.
FAU - Zipp, Frauke
AU  - Zipp F
AD  - Department of Neurology, University Medical Center Mainz, Mainz, Germany.
FAU - Hemmer, Bernhard
AU  - Hemmer B
AD  - Department of Neurology, Technische Universitat Munchen, Munich, Germany.
AD  - Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
FAU - Ziegler, Andreas
AU  - Ziegler A
AD  - Institut fur Medizinische Biometrie und Statistik, Universitat zu Lubeck, 
      Universitatsklinikum Schleswig-Holstein, Campus Lubeck, Lubeck, Germany.
AD  - Zentrum fur Klinische Studien, Universitat zu Lubeck, Lubeck, Germany.
AD  - School of Mathematics, Statistics and Computer Science, University of 
      KwaZulu-Natal, Pietermaritzburg, South Africa.
CN  - German Competence Network for Multiple Sclerosis (KKNMS)
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151026
PL  - United States
TA  - Genet Epidemiol
JT  - Genetic epidemiology
JID - 8411723
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Child
MH  - Exome/genetics
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Germany
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*genetics
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Young Adult
OTO - NOTNLM
OT  - ANKRD55 gene
OT  - HLA-DPB2 gene
OT  - Illumina exome array
OT  - MMEL1 gene
OT  - genome-wide association study
OT  - multiple sclerosis
EDAT- 2015/10/27 06:00
MHDA- 2016/08/30 06:00
CRDT- 2015/10/27 06:00
PHST- 2015/07/13 00:00 [received]
PHST- 2015/09/01 00:00 [revised]
PHST- 2015/09/02 00:00 [accepted]
PHST- 2015/10/27 06:00 [entrez]
PHST- 2015/10/27 06:00 [pubmed]
PHST- 2016/08/30 06:00 [medline]
AID - 10.1002/gepi.21933 [doi]
PST - ppublish
SO  - Genet Epidemiol. 2015 Dec;39(8):601-8. doi: 10.1002/gepi.21933. Epub 2015 Oct 26.