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

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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 - 1 Jul 2017

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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

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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).",

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

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

AU - King, C.

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).

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

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