Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with Multiple Sclerosis susceptibility

Gerry Z.M. Ma; Jim Stankovich; Trevor J. Kilpatrick; Michele D. Binder; Judith Field; Melanie Bahlo; David R. Booth; Simon Broadley; Matthew A. Brown; Brian L. Browning; Sharon R. Browning; Helmut Butzkueven; William M. Carroll; Patrick Danoy; Simon J. Foote; Lyn Griffiths; Robert N. Heard; Allan G. Kermode; Jeanette Lechner-Scott; Pablo Moscato; Victoria M. Perreau; Rodney J. Scott; Mark Slee; Graeme J. Stewart; Bruce V. Taylor; James Wiley

doi:10.1371/journal.pone.0016964

Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with Multiple Sclerosis susceptibility

Gerry Z.M. Ma, Jim Stankovich, Trevor J. Kilpatrick, Michele D. Binder, Judith Field^*, Melanie Bahlo, David R. Booth, Simon Broadley, Matthew A. Brown, Brian L. Browning, Sharon R. Browning, Helmut Butzkueven, William M. Carroll, Patrick Danoy, Simon J. Foote, Lyn Griffiths, Robert N. Heard, Allan G. Kermode, Jeanette Lechner-Scott, Pablo MoscatoVictoria M. Perreau, Rodney J. Scott, Mark Slee, Graeme J. Stewart, Bruce V. Taylor, James Wiley

^*Corresponding author for this work

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

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Abstract

Multiple sclerosis (MS) is a debilitating, chronic demyelinating disease of the central nervous system affecting over 2 million people worldwide. The TAM family of receptor tyrosine kinases (TYRO3, AXL and MERTK) have been implicated as important players during demyelination in both animal models of MS and in the human disease. We therefore conducted an association study to identify single nucleotide polymorphisms (SNPs) within genes encoding the TAM receptors and their ligands associated with MS. Analysis of genotype data from a genome-wide association study which consisted of 1618 MS cases and 3413 healthy controls conducted by the Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) revealed several SNPs within the MERTK gene (Chromosome 2q14.1, Accession Number NG_011607.1) that showed suggestive association with MS. We therefore interrogated 28 SNPs in MERTK in an independent replication cohort of 1140 MS cases and 1140 healthy controls. We found 12 SNPs that replicated, with 7 SNPs showing p-values of less than 10^-5 when the discovery and replication cohorts were combined. All 12 replicated SNPs were in strong linkage disequilibrium with each other. In combination, these data suggest the MERTK gene is a novel risk gene for MS susceptibility.

Original language	English
Article number	e16964
Journal	PLoS ONE
Volume	6
Issue number	2
DOIs	https://doi.org/10.1371/journal.pone.0016964
Publication status	Published - 2011
Externally published	Yes

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Ma, G. Z. M., Stankovich, J., Kilpatrick, T. J., Binder, M. D., Field, J., Bahlo, M., Booth, D. R., Broadley, S., Brown, M. A., Browning, B. L., Browning, S. R., Butzkueven, H., Carroll, W. M., Danoy, P., Foote, S. J., Griffiths, L., Heard, R. N., Kermode, A. G., Lechner-Scott, J., ... Wiley, J. (2011). Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with Multiple Sclerosis susceptibility. PLoS ONE, 6(2), Article e16964. https://doi.org/10.1371/journal.pone.0016964

@article{e552900db766481981deac755fc242bc,

title = "Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with Multiple Sclerosis susceptibility",

abstract = "Multiple sclerosis (MS) is a debilitating, chronic demyelinating disease of the central nervous system affecting over 2 million people worldwide. The TAM family of receptor tyrosine kinases (TYRO3, AXL and MERTK) have been implicated as important players during demyelination in both animal models of MS and in the human disease. We therefore conducted an association study to identify single nucleotide polymorphisms (SNPs) within genes encoding the TAM receptors and their ligands associated with MS. Analysis of genotype data from a genome-wide association study which consisted of 1618 MS cases and 3413 healthy controls conducted by the Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) revealed several SNPs within the MERTK gene (Chromosome 2q14.1, Accession Number NG_011607.1) that showed suggestive association with MS. We therefore interrogated 28 SNPs in MERTK in an independent replication cohort of 1140 MS cases and 1140 healthy controls. We found 12 SNPs that replicated, with 7 SNPs showing p-values of less than 10-5 when the discovery and replication cohorts were combined. All 12 replicated SNPs were in strong linkage disequilibrium with each other. In combination, these data suggest the MERTK gene is a novel risk gene for MS susceptibility.",

author = "Ma, {Gerry Z.M.} and Jim Stankovich and Kilpatrick, {Trevor J.} and Binder, {Michele D.} and Judith Field and Melanie Bahlo and Booth, {David R.} and Simon Broadley and Brown, {Matthew A.} and Browning, {Brian L.} and Browning, {Sharon R.} and Helmut Butzkueven and Carroll, {William M.} and Patrick Danoy and Foote, {Simon J.} and Lyn Griffiths and Heard, {Robert N.} and Kermode, {Allan G.} and Jeanette Lechner-Scott and Pablo Moscato and Perreau, {Victoria M.} and Scott, {Rodney J.} and Mark Slee and Stewart, {Graeme J.} and Taylor, {Bruce V.} and James Wiley",

year = "2011",

doi = "10.1371/journal.pone.0016964",

language = "English",

volume = "6",

journal = "PLoS ONE",

issn = "1932-6203",

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Ma, GZM, Stankovich, J, Kilpatrick, TJ, Binder, MD, Field, J, Bahlo, M, Booth, DR, Broadley, S, Brown, MA, Browning, BL, Browning, SR, Butzkueven, H, Carroll, WM, Danoy, P, Foote, SJ, Griffiths, L, Heard, RN, Kermode, AG, Lechner-Scott, J, Moscato, P, Perreau, VM, Scott, RJ, Slee, M, Stewart, GJ, Taylor, BV & Wiley, J 2011, 'Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with Multiple Sclerosis susceptibility', PLoS ONE, vol. 6, no. 2, e16964. https://doi.org/10.1371/journal.pone.0016964

TY - JOUR

T1 - Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with Multiple Sclerosis susceptibility

AU - Ma, Gerry Z.M.

AU - Stankovich, Jim

AU - Kilpatrick, Trevor J.

AU - Binder, Michele D.

AU - Field, Judith

AU - Bahlo, Melanie

AU - Booth, David R.

AU - Broadley, Simon

AU - Brown, Matthew A.

AU - Browning, Brian L.

AU - Browning, Sharon R.

AU - Butzkueven, Helmut

AU - Carroll, William M.

AU - Danoy, Patrick

AU - Foote, Simon J.

AU - Griffiths, Lyn

AU - Heard, Robert N.

AU - Kermode, Allan G.

AU - Lechner-Scott, Jeanette

AU - Moscato, Pablo

AU - Perreau, Victoria M.

AU - Scott, Rodney J.

AU - Slee, Mark

AU - Stewart, Graeme J.

AU - Taylor, Bruce V.

AU - Wiley, James

PY - 2011

Y1 - 2011

N2 - Multiple sclerosis (MS) is a debilitating, chronic demyelinating disease of the central nervous system affecting over 2 million people worldwide. The TAM family of receptor tyrosine kinases (TYRO3, AXL and MERTK) have been implicated as important players during demyelination in both animal models of MS and in the human disease. We therefore conducted an association study to identify single nucleotide polymorphisms (SNPs) within genes encoding the TAM receptors and their ligands associated with MS. Analysis of genotype data from a genome-wide association study which consisted of 1618 MS cases and 3413 healthy controls conducted by the Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) revealed several SNPs within the MERTK gene (Chromosome 2q14.1, Accession Number NG_011607.1) that showed suggestive association with MS. We therefore interrogated 28 SNPs in MERTK in an independent replication cohort of 1140 MS cases and 1140 healthy controls. We found 12 SNPs that replicated, with 7 SNPs showing p-values of less than 10-5 when the discovery and replication cohorts were combined. All 12 replicated SNPs were in strong linkage disequilibrium with each other. In combination, these data suggest the MERTK gene is a novel risk gene for MS susceptibility.

AB - Multiple sclerosis (MS) is a debilitating, chronic demyelinating disease of the central nervous system affecting over 2 million people worldwide. The TAM family of receptor tyrosine kinases (TYRO3, AXL and MERTK) have been implicated as important players during demyelination in both animal models of MS and in the human disease. We therefore conducted an association study to identify single nucleotide polymorphisms (SNPs) within genes encoding the TAM receptors and their ligands associated with MS. Analysis of genotype data from a genome-wide association study which consisted of 1618 MS cases and 3413 healthy controls conducted by the Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) revealed several SNPs within the MERTK gene (Chromosome 2q14.1, Accession Number NG_011607.1) that showed suggestive association with MS. We therefore interrogated 28 SNPs in MERTK in an independent replication cohort of 1140 MS cases and 1140 healthy controls. We found 12 SNPs that replicated, with 7 SNPs showing p-values of less than 10-5 when the discovery and replication cohorts were combined. All 12 replicated SNPs were in strong linkage disequilibrium with each other. In combination, these data suggest the MERTK gene is a novel risk gene for MS susceptibility.

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U2 - 10.1371/journal.pone.0016964

DO - 10.1371/journal.pone.0016964

M3 - Article

SN - 1932-6203

VL - 6

JO - PLoS ONE

JF - PLoS ONE

IS - 2

M1 - e16964

ER -

Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with Multiple Sclerosis susceptibility

Abstract

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