Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array
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Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array. / Dankowski, Theresa; Buck, Dorothea; Andlauer, Till F M; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Bettecken, Thomas; Chan, Andrew; Franke, Andre; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Herms, Stefan; Infante-Duarte, Carmen; Jöckel, Karl-Heinz; Kieseier, Bernd C; Knier, Benjamin; Knop, Matthias; Kümpfel, Tania; Lichtner, Peter; Lieb, Wolfgang; Lill, Christina M; Limmroth, Volker; Linker, Ralf A; Loleit, Verena; Meuth, Sven G; Moebus, Susanne; Müller-Myhsok, Bertram; Nischwitz, Sandra; Nöthen, Markus M; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Strauch, Konstantin; Stürner, Klarissa H; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Waldenberger, Melanie; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K; Ziemann, Ulf; Zipp, Frauke; Hemmer, Bernhard; Ziegler, Andreas; German Competence Network for Multiple Sclerosis (KKNMS).
in: GENET EPIDEMIOL, Jahrgang 39, Nr. 8, 12.2015, S. 601-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array
AU - Dankowski, Theresa
AU - Buck, Dorothea
AU - Andlauer, Till F M
AU - Antony, Gisela
AU - Bayas, Antonios
AU - Bechmann, Lukas
AU - Berthele, Achim
AU - Bettecken, Thomas
AU - Chan, Andrew
AU - Franke, Andre
AU - Gold, Ralf
AU - Graetz, Christiane
AU - Haas, Jürgen
AU - Hecker, Michael
AU - Herms, Stefan
AU - Infante-Duarte, Carmen
AU - Jöckel, Karl-Heinz
AU - Kieseier, Bernd C
AU - Knier, Benjamin
AU - Knop, Matthias
AU - Kümpfel, Tania
AU - Lichtner, Peter
AU - Lieb, Wolfgang
AU - Lill, Christina M
AU - Limmroth, Volker
AU - Linker, Ralf A
AU - Loleit, Verena
AU - Meuth, Sven G
AU - Moebus, Susanne
AU - Müller-Myhsok, Bertram
AU - Nischwitz, Sandra
AU - Nöthen, Markus M
AU - Paul, Friedemann
AU - Pütz, Michael
AU - Ruck, Tobias
AU - Salmen, Anke
AU - Stangel, Martin
AU - Stellmann, Jan-Patrick
AU - Strauch, Konstantin
AU - Stürner, Klarissa H
AU - Tackenberg, Björn
AU - Then Bergh, Florian
AU - Tumani, Hayrettin
AU - Waldenberger, Melanie
AU - Weber, Frank
AU - Wiendl, Heinz
AU - Wildemann, Brigitte
AU - Zettl, Uwe K
AU - Ziemann, Ulf
AU - Zipp, Frauke
AU - Hemmer, Bernhard
AU - Ziegler, Andreas
AU - German Competence Network for Multiple Sclerosis (KKNMS)
N1 - © 2015 WILEY PERIODICALS, INC.
PY - 2015/12
Y1 - 2015/12
N2 - 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 × 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.
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 × 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.
U2 - 10.1002/gepi.21933
DO - 10.1002/gepi.21933
M3 - SCORING: Journal article
C2 - 26497834
VL - 39
SP - 601
EP - 608
JO - GENET EPIDEMIOL
JF - GENET EPIDEMIOL
SN - 0741-0395
IS - 8
ER -