A variant in MCF2L is associated with osteoarthritis

Aaron G. Day-Williams; Lorraine Southam; Kalliope Panoutsopoulou; Nigel W. Rayner; Tonu Esko; Karol Estrada; Hafdis T. Helgadottir; Albert Hofman; Throvaldur Ingvarsson; Helgi Jonsson; Aime Keis; Hanneke J.M. Kerkhof; Gudmar Thorleifsson; Nigel K. Arden; Andrew Carr; Kay Chapman; Panos Deloukas; John Loughlin; Andrew McCaskie; William E.R. Ollier; Stuart H. Ralston; Timothy D. Spector; Gillian A. Wallis; J. Mark Wilkinson; Nadim Aslam; Fraser Birell; Ian Carluke; John Joseph; Ashok Rai; Mike Reed; Kirsten Walker; Sally A. Doherty; Ingileif Jonsdottir; Rose A. MacIewicz; Kenneth R. Muir; Andres Metspalu; Fernando Rivadeneira; Kari Stefansson; Unnur Styrkarsdottir; Andre G. Uitterlinden; Joyce B.J. Van Meurs; Weiya Zhang; Ana M. Valdes; Michael Doherty; Eleftheria Zeggini

doi:10.1016/j.ajhg.2011.08.001

A variant in MCF2L is associated with osteoarthritis

Aaron G. Day-Williams, Lorraine Southam, Kalliope Panoutsopoulou, Nigel W. Rayner, Tonu Esko, Karol Estrada, Hafdis T. Helgadottir, Albert Hofman, Throvaldur Ingvarsson, Helgi Jonsson, Aime Keis, Hanneke J.M. Kerkhof, Gudmar Thorleifsson, Nigel K. Arden, Andrew Carr, Kay Chapman, Panos Deloukas, John Loughlin, Andrew McCaskie, William E.R. OllierStuart H. Ralston, Timothy D. Spector, Gillian A. Wallis, J. Mark Wilkinson, Nadim Aslam, Fraser Birell, Ian Carluke, John Joseph, Ashok Rai, Mike Reed, Kirsten Walker, Sally A. Doherty, Ingileif Jonsdottir, Rose A. MacIewicz, Kenneth R. Muir, Andres Metspalu, Fernando Rivadeneira, Kari Stefansson, Unnur Styrkarsdottir, Andre G. Uitterlinden, Joyce B.J. Van Meurs, Weiya Zhang, Ana M. Valdes, Michael Doherty, Eleftheria Zeggini^*

^*Corresponding author for this work

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

95 Citations (Scopus)

Abstract

Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11-1.23], p = 2.1 × 10^-8) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.

Original language	English
Pages (from-to)	446-450
Number of pages	5
Journal	American Journal of Human Genetics
Volume	89
Issue number	3
DOIs	https://doi.org/10.1016/j.ajhg.2011.08.001
Publication status	Published - 9 Sept 2011

Bibliographical note

Funding Information:
The collection of GOAL samples was funded by Astra Zeneca UK. The author affiliated with AstraZeneca is an employee of AstraZeneca, a global research-based biopharmaceutical company focused on discovering, developing and marketing medicines for some of the world's most serious illnesses, and owns stocks or stock options and has a pending patent application in the company. The authors that are affiliated with deCODE genetics are all employees of deCODE, a biotechnology company that provides genetic testing services, and some own stocks or stock options in the company. Additional acknowledgments are in the Supplemental Data.

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10.1016/j.ajhg.2011.08.001

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Day-Williams, A. G., Southam, L., Panoutsopoulou, K., Rayner, N. W., Esko, T., Estrada, K., Helgadottir, H. T., Hofman, A., Ingvarsson, T., Jonsson, H., Keis, A., Kerkhof, H. J. M., Thorleifsson, G., Arden, N. K., Carr, A., Chapman, K., Deloukas, P., Loughlin, J., McCaskie, A., ... Zeggini, E. (2011). A variant in MCF2L is associated with osteoarthritis. American Journal of Human Genetics, 89(3), 446-450. https://doi.org/10.1016/j.ajhg.2011.08.001

@article{145717180fcb4b8f97d83c9dfd0d8f47,

title = "A variant in MCF2L is associated with osteoarthritis",

abstract = "Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11-1.23], p = 2.1 × 10-8) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.",

author = "Day-Williams, {Aaron G.} and Lorraine Southam and Kalliope Panoutsopoulou and Rayner, {Nigel W.} and Tonu Esko and Karol Estrada and Helgadottir, {Hafdis T.} and Albert Hofman and Throvaldur Ingvarsson and Helgi Jonsson and Aime Keis and Kerkhof, {Hanneke J.M.} and Gudmar Thorleifsson and Arden, {Nigel K.} and Andrew Carr and Kay Chapman and Panos Deloukas and John Loughlin and Andrew McCaskie and Ollier, {William E.R.} and Ralston, {Stuart H.} and Spector, {Timothy D.} and Wallis, {Gillian A.} and Wilkinson, {J. Mark} and Nadim Aslam and Fraser Birell and Ian Carluke and John Joseph and Ashok Rai and Mike Reed and Kirsten Walker and Doherty, {Sally A.} and Ingileif Jonsdottir and MacIewicz, {Rose A.} and Muir, {Kenneth R.} and Andres Metspalu and Fernando Rivadeneira and Kari Stefansson and Unnur Styrkarsdottir and Uitterlinden, {Andre G.} and {Van Meurs}, {Joyce B.J.} and Weiya Zhang and Valdes, {Ana M.} and Michael Doherty and Eleftheria Zeggini",

note = "Funding Information: The collection of GOAL samples was funded by Astra Zeneca UK. The author affiliated with AstraZeneca is an employee of AstraZeneca, a global research-based biopharmaceutical company focused on discovering, developing and marketing medicines for some of the world's most serious illnesses, and owns stocks or stock options and has a pending patent application in the company. The authors that are affiliated with deCODE genetics are all employees of deCODE, a biotechnology company that provides genetic testing services, and some own stocks or stock options in the company. Additional acknowledgments are in the Supplemental Data. ",

year = "2011",

month = sep,

day = "9",

doi = "10.1016/j.ajhg.2011.08.001",

language = "English",

volume = "89",

pages = "446--450",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

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Day-Williams, AG, Southam, L, Panoutsopoulou, K, Rayner, NW, Esko, T, Estrada, K, Helgadottir, HT, Hofman, A, Ingvarsson, T, Jonsson, H, Keis, A, Kerkhof, HJM, Thorleifsson, G, Arden, NK, Carr, A, Chapman, K, Deloukas, P, Loughlin, J, McCaskie, A, Ollier, WER, Ralston, SH, Spector, TD, Wallis, GA, Wilkinson, JM, Aslam, N, Birell, F, Carluke, I, Joseph, J, Rai, A, Reed, M, Walker, K, Doherty, SA, Jonsdottir, I, MacIewicz, RA, Muir, KR, Metspalu, A, Rivadeneira, F, Stefansson, K, Styrkarsdottir, U, Uitterlinden, AG, Van Meurs, JBJ, Zhang, W, Valdes, AM, Doherty, M & Zeggini, E 2011, 'A variant in MCF2L is associated with osteoarthritis', American Journal of Human Genetics, vol. 89, no. 3, pp. 446-450. https://doi.org/10.1016/j.ajhg.2011.08.001

TY - JOUR

T1 - A variant in MCF2L is associated with osteoarthritis

AU - Day-Williams, Aaron G.

AU - Southam, Lorraine

AU - Panoutsopoulou, Kalliope

AU - Rayner, Nigel W.

AU - Esko, Tonu

AU - Estrada, Karol

AU - Helgadottir, Hafdis T.

AU - Hofman, Albert

AU - Ingvarsson, Throvaldur

AU - Jonsson, Helgi

AU - Keis, Aime

AU - Kerkhof, Hanneke J.M.

AU - Thorleifsson, Gudmar

AU - Arden, Nigel K.

AU - Carr, Andrew

AU - Chapman, Kay

AU - Deloukas, Panos

AU - Loughlin, John

AU - McCaskie, Andrew

AU - Ollier, William E.R.

AU - Ralston, Stuart H.

AU - Spector, Timothy D.

AU - Wallis, Gillian A.

AU - Wilkinson, J. Mark

AU - Aslam, Nadim

AU - Birell, Fraser

AU - Carluke, Ian

AU - Joseph, John

AU - Rai, Ashok

AU - Reed, Mike

AU - Walker, Kirsten

AU - Doherty, Sally A.

AU - Jonsdottir, Ingileif

AU - MacIewicz, Rose A.

AU - Muir, Kenneth R.

AU - Metspalu, Andres

AU - Rivadeneira, Fernando

AU - Stefansson, Kari

AU - Styrkarsdottir, Unnur

AU - Uitterlinden, Andre G.

AU - Van Meurs, Joyce B.J.

AU - Zhang, Weiya

AU - Valdes, Ana M.

AU - Doherty, Michael

AU - Zeggini, Eleftheria

N1 - Funding Information: The collection of GOAL samples was funded by Astra Zeneca UK. The author affiliated with AstraZeneca is an employee of AstraZeneca, a global research-based biopharmaceutical company focused on discovering, developing and marketing medicines for some of the world's most serious illnesses, and owns stocks or stock options and has a pending patent application in the company. The authors that are affiliated with deCODE genetics are all employees of deCODE, a biotechnology company that provides genetic testing services, and some own stocks or stock options in the company. Additional acknowledgments are in the Supplemental Data.

PY - 2011/9/9

Y1 - 2011/9/9

N2 - Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11-1.23], p = 2.1 × 10-8) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.

AB - Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11-1.23], p = 2.1 × 10-8) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.

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U2 - 10.1016/j.ajhg.2011.08.001

DO - 10.1016/j.ajhg.2011.08.001

M3 - Article

C2 - 21871595

AN - SCOPUS:80052736294

SN - 0002-9297

VL - 89

SP - 446

EP - 450

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 3

ER -

A variant in MCF2L is associated with osteoarthritis

Abstract

Bibliographical note

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