Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array

German Competence Network for Multiple Sclerosis (KKNMS); Theresa Dankowski; Dorothea Buck; Till F M Andlauer; Gisela Antony; Antonios Bayas; Lukas Bechmann; Achim Berthele; Thomas Bettecken; Andrew Chan; Andre Franke; Ralf Gold; Christiane Graetz; Jürgen Haas; Michael Hecker; Stefan Herms; Carmen Infante-Duarte; Karl-Heinz Jöckel; Bernd C Kieseier; Benjamin Knier; Matthias Knop; Tania Kümpfel; Peter Lichtner; Wolfgang Lieb; Christina M Lill; Volker Limmroth; Ralf A Linker; Verena Loleit; Sven G Meuth; Susanne Moebus; Bertram Müller-Myhsok; Sandra Nischwitz; Markus M Nöthen; Friedemann Paul; Michael Pütz; Tobias Ruck; Anke Salmen; Martin Stangel; Jan-Patrick Stellmann; Konstantin Strauch; Klarissa H Stürner; Björn Tackenberg; Florian Then Bergh; Hayrettin Tumani; Melanie Waldenberger; Frank Weber; Heinz Wiendl; Brigitte Wildemann; Uwe K Zettl; Ulf Ziemann; Andreas Ziegler

doi:10.1002/gepi.21933

Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array

German Competence Network for Multiple Sclerosis (KKNMS), Theresa Dankowski, Dorothea Buck, Till F M Andlauer, Gisela Antony, Antonios Bayas, Lukas Bechmann, Achim Berthele, Thomas Bettecken, Andrew Chan, Andre Franke, Ralf Gold, Christiane Graetz, Jürgen Haas, Michael Hecker, Stefan Herms, Carmen Infante-Duarte, Karl-Heinz Jöckel, Bernd C Kieseier, Benjamin KnierMatthias Knop, Tania Kümpfel, Peter Lichtner, Wolfgang Lieb, Christina M Lill, Volker Limmroth, Ralf A Linker, Verena Loleit, Sven G Meuth, Susanne Moebus, Bertram Müller-Myhsok, Sandra Nischwitz, Markus M Nöthen, Friedemann Paul, Michael Pütz, Tobias Ruck, Anke Salmen, Martin Stangel, Jan-Patrick Stellmann, Konstantin Strauch, Klarissa H Stürner, Björn Tackenberg, Florian Then Bergh, Hayrettin Tumani, Melanie Waldenberger, Frank Weber, Heinz Wiendl, Brigitte Wildemann, Uwe K Zettl, Ulf Ziemann, Andreas Ziegler

Abstract

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.

Original language	English
Journal	Genetic Epidemiology
Volume	39
Issue number	8
Pages (from-to)	601-8
Number of pages	8
ISSN	0741-0395
DOIs	https://doi.org/10.1002/gepi.21933
Publication status	Published - 2015

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German Competence Network for Multiple Sclerosis (KKNMS), Dankowski, T., Buck, D., Andlauer, T. F. M., Antony, G., Bayas, A., Bechmann, L., Berthele, A., Bettecken, T., Chan, A., Franke, A., Gold, R., Graetz, C., Haas, J., Hecker, M., Herms, S., Infante-Duarte, C., Jöckel, K-H., Kieseier, B. C., ... Ziegler, A. (2015). Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array. Genetic Epidemiology, 39(8), 601-8. https://doi.org/10.1002/gepi.21933

@article{95a24975fd6b4994aa290bf445ceac9c,

title = "Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array",

abstract = "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. ",

author = "{German Competence Network for Multiple Sclerosis (KKNMS)} and Theresa Dankowski and Dorothea Buck and Andlauer, {Till F M} and Gisela Antony and Antonios Bayas and Lukas Bechmann and Achim Berthele and Thomas Bettecken and Andrew Chan and Andre Franke and Ralf Gold and Christiane Graetz and J{\"u}rgen Haas and Michael Hecker and Stefan Herms and Carmen Infante-Duarte and Karl-Heinz J{\"o}ckel and Kieseier, {Bernd C} and Benjamin Knier and Matthias Knop and Tania K{\"u}mpfel and Peter Lichtner and Wolfgang Lieb and Lill, {Christina M} and Volker Limmroth and Linker, {Ralf A} and Verena Loleit and Meuth, {Sven G} and Susanne Moebus and Bertram M{\"u}ller-Myhsok and Sandra Nischwitz and N{\"o}then, {Markus M} and Friedemann Paul and Michael P{\"u}tz and Tobias Ruck and Anke Salmen and Martin Stangel and Jan-Patrick Stellmann and Konstantin Strauch and St{\"u}rner, {Klarissa H} and Bj{\"o}rn Tackenberg and {Then Bergh}, Florian and Hayrettin Tumani and Melanie Waldenberger and Frank Weber and Heinz Wiendl and Brigitte Wildemann and Zettl, {Uwe K} and Ulf Ziemann and Andreas Ziegler",

note = "{\textcopyright} 2015 WILEY PERIODICALS, INC.",

year = "2015",

doi = "10.1002/gepi.21933",

language = "English",

volume = "39",

pages = "601--8",

journal = "Genetic Epidemiology",

issn = "0741-0395",

number = "8",

}

German Competence Network for Multiple Sclerosis (KKNMS), Dankowski, T, Buck, D, Andlauer, TFM, Antony, G, Bayas, A, Bechmann, L, Berthele, A, Bettecken, T, Chan, A, Franke, A, Gold, R, Graetz, C, Haas, J, Hecker, M, Herms, S, Infante-Duarte, C, Jöckel, K-H, Kieseier, BC, Knier, B, Knop, M, Kümpfel, T, Lichtner, P, Lieb, W, Lill, CM, Limmroth, V, Linker, RA, Loleit, V, Meuth, SG, Moebus, S, Müller-Myhsok, B, Nischwitz, S, Nöthen, MM, Paul, F, Pütz, M, Ruck, T, Salmen, A, Stangel, M, Stellmann, J-P, Strauch, K, Stürner, KH, Tackenberg, B, Then Bergh, F, Tumani, H, Waldenberger, M, Weber, F, Wiendl, H, Wildemann, B, Zettl, UK, Ziemann, U & Ziegler, A 2015, 'Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array', Genetic Epidemiology, vol. 39, no. 8, pp. 601-8. https://doi.org/10.1002/gepi.21933

TY - JOUR

T1 - Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array

AU - German Competence Network for Multiple Sclerosis (KKNMS)

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 - Ziegler, Andreas

PY - 2015

Y1 - 2015

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 - Journal articles

C2 - 26497834

SN - 0741-0395

VL - 39

SP - 601

EP - 608

JO - Genetic Epidemiology

JF - Genetic Epidemiology

IS - 8

ER -

Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array

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