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; The Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene)

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. TaylorK. Vandenbroeck, M. Comabella, F. M. Boneschi, C. King, The Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene)

Computational And Systems Biology

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

23 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

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., ... The Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) (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

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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).",

author = "S. Mahurkar and M. Moldovan and V. Suppiah and M. Sorosina and F. Clarelli and G. Liberatore and S. Malhotra and X. Montalban and A. Antig{\"u}edad and M. Krupa and Jokubaitis, {V. G.} and McKay, {F. C.} and Gatt, {P. N.} and Fabis-Pedrini, {M. J.} and V. Martinelli and G. Comi and J. Lechner-Scott and Kermode, {A. G.} and M. Slee and Taylor, {B. V.} and K. Vandenbroeck and M. Comabella and Boneschi, {F. M.} and C. King and {The Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene)}",

note = "Funding Information: This work was supported by a University of South Australia, Division of Health Sciences Research Development Grant.",

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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 & The Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) 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

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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.

AU - The Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene)

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PY - 2017/7/1

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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).

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

Abstract

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