Response to interferon-beta treatment in multiple sclerosis patients: A genome-wide association study

S. Mahurkar; M. Moldovan; V. Suppiah; M. Sorosina; F. Clarelli; G. Liberatore; S. Malhotra; X. Montalban; A. Antigüedad; M. Krupa; V. G. Jokubaitis; F. C. McKay; P. N. Gatt; M. J. Fabis-Pedrini; V. Martinelli; G. Comi; J. Lechner-Scott; A. G. Kermode; M. Slee; B. V. Taylor; K. Vandenbroeck; M. Comabella; F. M. Boneschi; C. King

doi:10.1038/tpj.2016.20

Response to interferon-beta treatment in multiple sclerosis patients: A genome-wide association study

S. Mahurkar
, M. Moldovan
, V. Suppiah
, M. Sorosina
, F. Clarelli
, G. Liberatore
, S. Malhotra
, X. Montalban
, A. Antigüedad
, M. Krupa
, V. G. Jokubaitis
, F. C. McKay
, P. N. Gatt
, M. J. Fabis-Pedrini
, V. Martinelli
, G. Comi
, J. Lechner-Scott
, A. G. Kermode
, M. Slee
, B. V. Taylor

K. Vandenbroeck, M. Comabella, F. M. Boneschi, C. King

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-β) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-β treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-β-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 106) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10 5) and near ZNF697 (combined P-value 8.15 × 10 5).

Original language	English
Pages (from-to)	312-318
Number of pages	7
Journal	Pharmacogenomics Journal
Volume	17
Issue number	4
DOIs	https://doi.org/10.1038/tpj.2016.20
Publication status	Published or Issued - 1 Jul 2017
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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10.1038/tpj.2016.20

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Mahurkar, S., Moldovan, M., Suppiah, V., Sorosina, M., Clarelli, F., Liberatore, G., Malhotra, S., Montalban, X., Antigüedad, A., Krupa, M., Jokubaitis, V. G., McKay, F. C., Gatt, P. N., Fabis-Pedrini, M. J., Martinelli, V., Comi, G., Lechner-Scott, J., Kermode, A. G., Slee, M., ... King, C. (2017). Response to interferon-beta treatment in multiple sclerosis patients: A genome-wide association study. Pharmacogenomics Journal, 17(4), 312-318. https://doi.org/10.1038/tpj.2016.20

@article{2058093764d4496bbe85ac6f4b3a7b2e,

title = "Response to interferon-beta treatment in multiple sclerosis patients: A genome-wide association study",

abstract = "Up to 50\% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-β) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-β treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-β-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 106) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10 5) and near ZNF697 (combined P-value 8.15 × 10 5).",

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Mahurkar, S, Moldovan, M, Suppiah, V, Sorosina, M, Clarelli, F, Liberatore, G, Malhotra, S, Montalban, X, Antigüedad, A, Krupa, M, Jokubaitis, VG, McKay, FC, Gatt, PN, Fabis-Pedrini, MJ, Martinelli, V, Comi, G, Lechner-Scott, J, Kermode, AG, Slee, M, Taylor, BV, Vandenbroeck, K, Comabella, M, Boneschi, FM & King, C 2017, 'Response to interferon-beta treatment in multiple sclerosis patients: A genome-wide association study', Pharmacogenomics Journal, vol. 17, no. 4, pp. 312-318. https://doi.org/10.1038/tpj.2016.20

TY - JOUR

T1 - Response to interferon-beta treatment in multiple sclerosis patients

T2 - A genome-wide association study

AU - Mahurkar, S.

AU - Moldovan, M.

AU - Suppiah, V.

AU - Sorosina, M.

AU - Clarelli, F.

AU - Liberatore, G.

AU - Malhotra, S.

AU - Montalban, X.

AU - Antigüedad, A.

AU - Krupa, M.

AU - Jokubaitis, V. G.

AU - McKay, F. C.

AU - Gatt, P. N.

AU - Fabis-Pedrini, M. J.

AU - Martinelli, V.

AU - Comi, G.

AU - Lechner-Scott, J.

AU - Kermode, A. G.

AU - Slee, M.

AU - Taylor, B. V.

AU - Vandenbroeck, K.

AU - Comabella, M.

AU - Boneschi, F. M.

AU - King, C.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-β) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-β treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-β-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 106) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10 5) and near ZNF697 (combined P-value 8.15 × 10 5).

AB - Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-β) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-β treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-β-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 106) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10 5) and near ZNF697 (combined P-value 8.15 × 10 5).

UR - https://www.scopus.com/pages/publications/84977274571

U2 - 10.1038/tpj.2016.20

DO - 10.1038/tpj.2016.20

M3 - Article

C2 - 27001119

AN - SCOPUS:84977274571

SN - 1470-269X

VL - 17

SP - 312

EP - 318

JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

IS - 4

ER -

Response to interferon-beta treatment in multiple sclerosis patients: A genome-wide association study

Abstract

ASJC Scopus subject areas

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