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

ANZgene Consortium, Lotti Tajouri

Research output: Contribution to journalArticleResearchpeer-review

11 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 languageEnglish
Pages (from-to)312-318
Number of pages7
JournalPharmacogenomics Journal
Volume17
Issue number4
DOIs
Publication statusPublished - 1 Jul 2017

Fingerprint

Interferon-beta
Genome-Wide Association Study
Multiple Sclerosis
Genetic Markers
GTPase-Activating Proteins
Therapeutics
Disease Management
Histidine
Spain
Italy
Single Nucleotide Polymorphism

Cite this

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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 = "{ANZgene Consortium} and 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 Lotti Tajouri",
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Response to interferon-beta treatment in multiple sclerosis patients : A genome-wide association study. / ANZgene Consortium ; Tajouri, Lotti.

In: Pharmacogenomics Journal, Vol. 17, No. 4, 01.07.2017, p. 312-318.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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

T2 - A genome-wide association study

AU - ANZgene Consortium

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 - Tajouri, Lotti

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).

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U2 - 10.1038/tpj.2016.20

DO - 10.1038/tpj.2016.20

M3 - Article

VL - 17

SP - 312

EP - 318

JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

SN - 1470-269X

IS - 4

ER -