Newcastle University

Introduction

I did my PhD in developmental biology at Leeds University and subsequently carried out postdoctoral studies with Professor Bryan Sykes at the Institute of Molecular Medicine at Oxford University. These involved a molecular genetic analysis of monogenic and polygenic diseases of the musculoskeletal system. I subsequently obtained a fellowship from the Arthritis Research Campaign and established a group at the Wellcome Trust Centre for Human Genetics. At that point my focus became the genetic analysis of osteoarthritis (OA) and in 2008 I moved to Newcastle as Professor of Musculoskeletal Research.

Roles and Responsibilities

• Head of the Osteoarthritis Genetics Group, Institute of Cellular Medicine (ICM)
• Mentor for early-stage independent investigators, ICM
• President Elect of OARSI, the principal international OA research society

Qualifications

• 1999 MA University of Oxford
• 1991 PhD Molecular and Developmental Biology, University of Leeds
• 1987 BSc (Hon) Biochemistry, Liverpool John Moores University

Previous Positions

• 2002-2007 University Lecturer in Musculoskeletal Sciences, University of Oxford
• 1997-2002 Arthritis Research Campaign Fellow, University of Oxford
• 1995-1997 Postdoctoral Scientist, Wellcome Trust Centre for Human Genetics, University of Oxford
• 1991-1995 Postdoctoral Scientist, Institute of Molecular Medicine, University of Oxford

Memberships

I am a member of the following professional societies:

• Osteoarthritis Research Society International (www.oarsi.org/)
• British Society for Genetic Medicine (www.bsgm.org.uk/)
• British Society for Matrix Biology (www.bsmb.ac.uk/)
• Skeletal Dysplasia Group (www.skeletaldysplasiagroup.org.uk/)

Research Interests

My groups principal research focus is identifying and then characterising those genes that confer risk towards the development and progression of osteoarthritis.

Osteoarthritis (OA) is a common disease involving loss of normal joint function. It is painful, debilitating and impacts not only on the quality of life but also on the length of life (http://www.arthritisresearchuk.org/arthritis-information/conditions/osteoarthritis.aspx).

The form of the disease that we mostly work on is the one that arises without an obvious cause, such as in the absence of a clear injury. This form of OA, known as primary OA, affects older people.

A number of epidemiological studies have demonstrated that OA has a large genetic component.

Through the application of powerful genome-wide association scans involving tens of thousands of OA patients we have identified a number genes harbouring susceptibility alleles for OA, including the genes CHST11, GDF5, DIO2 and HBP1.

Our efforts are directed toward comprehensive functional analysis of the associated variants within these genes, and in others that are emerging from ongoing scans.

Group Members:

• Dr Louise Reynard - research fellow
• Dr Fiona Gee - postdoctoral scientist
• Dr Michael Rushton - postdoctoral scientist
• Dr Colin Shepherd - postdoctoral scientist
• Madhu Ratnayake - research assistant
• Clare Clubbs - research technician
• Lucy Gentles - research technician
• Emma Rogers - PhD student
• Kath Johnson - PhD student
• Emma Raine - PhD student
• Fabio D'Agostino - PhD student

Current Work

In addition to my OA research I am also one of the lead investigators for CIMA - the MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing. This is a collaboration between the Universities of Liverpool, Newcastle and Sheffield. CIMA runs until 2017 and further details can be found at the CIMA website - www.cimauk.org/ 

Within CIMA I am the lead for work package 1, which is directed toward the integration of research programmes in molecular and cellular mechanisms. I co-supervise two CIMA funded PhD students, one based in Liverpool (Luke Tregilgas) and the other in Sheffield (Amy Easthope).

I am also one of the lead investigators for D-BOARD, a European Union FP7-funded 5-year collaborative project directed toward OA biomarker development (http://www.d-board.eu/dboard/index.aspx). D-BOARD also runs until 2017.

Within D-BOARD I am the lead for work package 3, which is directed to the use of genomics, epigenomics and transcriptomics for OA biomarker development.

Many of the loci that my group investigate harbour polymorphisms that influence gene expression and this has stimulated our study of the tissue-specific effects of cis polymorphism on allelic expression imbalance.

The technical expertise that my group employs includes:

• genetic association analysis by case-control and family-based methods
• overall gene expression analysis using microarrays and RNAseq
• gene expression analysis at the allelic level
• in vitro studies of gene expression using luciferase reporter assays and EMSAs
• analysis of cell-signalling pathways by protein expression studies and western analysis
• identification and characterisation of trans-acting factors using ChIP
• characterisation of cis and trans factors by RNA knockdown and overexpression 
• targeted epigenetic analysis of CpG sites in candidate loci using cell lines and tissue from human donors
• genome-wide epigenetic analysis using methylation arrays
• investigation of gene and protein expression in transformed cells, primary cells and mesenchymal stem cells
• the identification of novel mutations in Mendelian pedigrees by exome sequencing
• the identification of rare polymorphisms in OA susceptibility loci by next generation sequencing

Future Research

My groups main effort for the next several years will be to carry out detailed functional studies of the loci identified such that we can understand clearly how the associated variants influence disease risk. This information will then be applied to develop improved diagnostic and prognostic tools and to facilitate the development of new intervention strategies, including novel therapeutics. 

Postgraduate Supervision

I have considerable experience of postgraduate supervision and encourage undergraduates who have a keen interest in genetics and the functional analysis of disease loci to get in touch.

Esteem Indicators

The Osteoarthritis Research Society International (OARSI, http://www.oarsi.org/) is the major international OA research society and within it I perform a number of roles:

• President (2015-2017)
• President-elect (2013-2015)
• Secretary General (2010-2013)
• Member of the Board of Directors (2007-2017)
• Chair of the Ethics Committee (2012-2015)
• Program committee member and session chair, OARSI Congress 2012, 2013 and 2014
• Moderator for the pre-congress workshop on "Genetics, genomics and functional analysis of OA susceptibility", OARSI Congress, Barcelona, 2012

Other esteem indicators unrelated to OARSI include:

• Member of the Fellowship Implementation Committee of Arthritis Research UK (2007-2013)
• Chair and organiser of the second OA Biomarkers workshop, Atlanta, USA, 2010
• Member of the Editorial Boards of the journals Osteoarthritis & Cartilage, BMC Musculoskeletal Disorders, Longevity & Lifespan
• Expert reviewer for INSERM, France, and scientific advisor to the NIH, USA
• Presented my groups research, and overviews of the research area, at international conferences in Europe, North America and Asia (over 40 oral presentations in the past 5 years) 

Funding

I have been the principal investigator (PI) for 25 grants and the co-investigator (CI) for an additional 9, with a total grant income of £15 million.

I am currently the PI for 6 grants and the CI for 4 grants.

These 10 grants come from the MRC, Arthritis Research UK, the European Union, the Nuffield Foundation, the JGW Patterson Foundation and the William Harker Foundation.

Undergraduate Teaching

• Lecturer on the BSc Biomedical Sciences course (BMS3010) and on the BSc Biomedical Genetics course (BGM3061)
• Supervisor for undergraduate laboratory projects
• Undergraduate project marker
• MBBS marker
• Tutor for Biomedical Scientists 

Postgraduate Teaching

• Lecturer for the MRes course in Musculoskeletal Biology (MMB8002)
• Lecturer for the MRes course on the Genetics of Common Diseases (MMB8014)
• Supervisor for MRes laboratory projects

• Reynard LN, Loughlin J. Insights from human genetic studies into the pathways involved in osteoarthritis. Nature Reviews Rheumatology 2013, Epub ahead of print.
• Syddall CM, Reynard LN, Young DA, Loughlin J. The Identification of Trans-acting Factors That Regulate the Expression of GDF5 via the Osteoarthritis Susceptibility SNP rs143383. PLoS Genetics 2013, 9(6), e1003557.
• Dodd AW, Syddall CM, Loughlin J. A rare variant in the osteoarthritis-associated locus GDF5 is functional and reveals a site that can be manipulated to modulate GDF5 expression. European Journal of Human Genetics 2013, 21(5), 517-521.
• Raine EV, Dodd AW, Reynard LN, Loughlin J. Allelic expression analysis of the osteoarthritis susceptibility gene COL11A1 in human joint tissues. BMC Musculoskeletal Disorders 2013, 14, 85.
• Reynard LN, Loughlin J. The genetics and functional analysis of primary osteoarthritis susceptibility. Expert Reviews in Molecular Medicine 2013, 15, e2-e16.
• Hudson G, Panoutsopoulou K, Wilson I, Southam L, Rayner NW, Arden N, Birrell F, Carluke I, Carr A, Chapman K, Deloukas P, Doherty M, McCaskie A, Ollier WE, Ralston SH, Reed MR, Spector TD, Valdes AM, Wallis GA, Wilkinson JM, Zeggini E, Samuels DC, Loughlin J, Chinnery PF, arcOGEN Consortium. No evidence of an association between mitochondrial DNA variants and osteoarthritis in 7393 cases and 5122 controls. Annals of Rheumatic Diseases 2013, 72(1), 136-139.
• Elliott KS, Chapman K, Day-Williams A, Panoutsopoulou K, Southam L, Lindgren CM, The GIANT Consortium, Arden N, Aslam N, Birrell F, Carluke I, Carr A, Deloukas P, Doherty M, Loughlin J, McCaskie A, Ollier WE, Rai A, Ralston S, Reed MR, Spector TD, Valdes AM, Wallis GA, Wilkinson M, The arcOGEN Consortium, Zeggini E. Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data. Annals of the Rheumatic Diseases 2013, 72(6), 935-941.
• Evangelou E, Kerkhof HJ, Styrkarsdottir U, Ntzani EE, Bos SD, Esko T, Evans DS, Metrustry S, Panoutsopoulou K, Ramos YFM, Thorleifsson G, Tsilidis KK, arcOGEN Consortium, Arden N, Aslam N, Bellamy N, Birrell F, Blanco FJ, Carr A, Chapman K, Day-Williams AG, Deloukas P, Doherty M, Engstrom G, Helgadottir HT, Hofman A, Ingvarsson T, Jonsson H, Keis A, Keurentjes JC, Kloppenburg M, Lind PA, McCaskie A, Martin NG, Milani L, Montgomery GW, Nelissen RGHH, Nevitt MC, Nilsson PM, Ollier WER, Parimi N, Rai A, Ralston SH, Reed MR, Riancho JA, Rivadeneira F, Rodriguez-Fontenla C, Southam L, Thorsteinsdottir U, Tsezou A, Wallis GA, Wilkinson JM, Gonzalez A, Lane NE, Lohmander LS, Loughlin J, Metspalu A, Uitterlinden AG, Jonsdottir I, Stefansson K, Slagboom PE, Zeggini E, Meulenbelt I, Ioannidis JPA, Spector TD, van Meurs JBJ, Valdes AM. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip. Annals of the Rheumatic Diseases 2013, Epub ahead of print.
• Reynard LN, Loughlin J. Genetics and epigenetics of osteoarthritis. Maturitas 2012, 71(3), 200–204.
• Raine EVA, Wreglesworth N, Dodd AW, Reynard LN, Loughlin J. Gene expression analysis reveals HBP1 as a key target for the osteoarthritis susceptibility locus that maps to chromosome 7q22. Annals of the Rheumatic Diseases 2012, 71(12), 2020-2027.
• Ratnayake M, Reynard LN, Raine EVA, Santibanez-Koref M, Loughlin J. Allelic expression analysis of the osteoarthritis susceptibility locus that maps to MICAL3. BMC Medical Genetics 2012, 13(1), 12.
• Horvath R, Holinski Feder E, Neeve VC, Pyle A, Griffin H, Ashok D, Foley C, Hudson G, Rautenstrauss B, Nürnberg G, Nürnberg P, Kortler J, Neitzel B, Bäßmann I, Rahman T, Keavney B, Loughlin J, Hambleton S, Schoser B, Lochmüller H, Santibanez Koref M, Chinnery PF. A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy. Movement Disorders 2012, 76(6), 789-793.
• Xu Y, Barter MJ, Swan DC, Rankin KS, Rowan AD, Santibanez-Koref M, Loughlin J, Young DA. Identification of the pathogenic pathways in osteoarthritic hip cartilage: commonality and discord between hip and knee OA. Osteoarthritis and Cartilage 2012, 20(9), 1029-1038.
• Bos SD, Bovée JV, Duijnisveld BJ, Raine EV, van Dalen WJ, Ramos YF, van der Breggen R, Nelissen RG, Slagboom PE, Loughlin J, Meulenbelt I. Increased type II deiodinase protein in OA-affected cartilage and allelic imbalance of OA risk polymorphism rs225014 at DIO2 in human OA joint tissues. Annals of the Rheumatic Diseases 2012, 71(7), 1254-1258.
• Rodriguez-Fontenla C, Carr A, Gomez-Reino JJ, Tsezou A, Loughlin J, Gonzalez A. Association of a BMP5 microsatellite with knee osteoarthritis: case-control study. Arthritis Research & Therapy 2012, 14(6), R257.
• Zeggini E, Panoutsopoulou K, Southam L, Rayner NW, Day-Williams AG, Lopes MC, Boraska V, Esko T, Evangelou E, Hofman A, Houwing-Duistermaat JJ, Ingvarsson T, Jonsdottir I, Jonsson H, Kerkhof HJM, Kloppenburg M, Bos SD, Mangino M, Metrustry S, Slagboom PE, Thorleifsson G, Raine EVA, Ratnayake M, Ricketts M, Beazley C, Blackburn H, Bumpstead S, Elliott KS, Hunt SE, Potter SC, Shin SY, Yadav VK, Zhai GJ, Sherburn K, Dixon K, Arden E, Aslam N, Battley PK, Carluke I, Doherty S, Gordon A, Joseph J, Keen R, Koller NC, Mitchell S, O'Neill F, Paling E, Reed MR, Rivadeneira F, Swift D, Walker K, Watkins B, Wheeler M, Birrell F, Ioannidis JPA, Meulenbelt I, Metspalu A, Rai A, Salter D, Stefansson K, Styrkarsdottir U, Uitterlinden AG, van Meurs JBJ, Chapman K, Deloukas P, Ollier WER, Wallis GA, Arden N, Carr A, Doherty M, McCaskie A, Wilkinson JM, Ralston SH, Valdes AM, Spector TD, Loughlin J. Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study. Lancet 2012, 380(9844), 815-823.
• Reynard LN, Bui C, Canty-Laird EG, Young DA, Loughlin J. Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation. Human Molecular Genetics 2011, 20(17), 3450-3460.
• Dodd AW, Rodriguez-Fontenla C, Calaza M, Carr A, Gomez-Reino JJ, Tsezou A, Reynard LN, Gonzalez A, Loughlin J. Deep sequencing of GDF5 reveals the absence of rare variants at this important osteoarthritis susceptibility locus. Osteoarthritis and Cartilage 2011, 19(4), 430-434.
• Loughlin J. Genetics of osteoarthritis. Current Opinion in Rheumatology 2011, 23(5), 479-483.
• Loughlin J. Knee osteoarthritis, lumbar-disc degeneration and developmental dysplasia of the hip - an emerging genetic overlap. Arthritis Research & Therapy 2011, 13(2), 108.
• 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, arcOGEN Consortium, 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. A variant in MCF2L is associated with osteoarthritis. American Journal of Human Genetics 2011, 89(3), 446-450.
• Dickinson RE, Griffin H, Bigley V, Reynard LN, Hussain R, Haniffa M, Lakey JH, Rahman T, Wang XN, McGovern N, Pagan S, Cookson S, McDonald D, Chua I, Wallis J, Cant A, Wright M, Keavney B, Chinnery PF, Loughlin J, Hambleton S, Santibanez-Koref M, Collin M. Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood 2011, 118(10), 2656-2658.
• Meulenbelt I, Kraus VB, Sandell LJ, Loughlin J. Summary of the OA biomarkers workshop 2010 – genetics and genomics: new targets in OA. Osteoarthritis and Cartilage 2011, 19(9), 1091-1094.
• Loughlin J. Osteoarthritis: All types of trouble-defining OA in the genomic era. Nature Reviews Rheumatology 2011, 7(4), 200-202.
• Loughlin J. Genetic indicators and susceptibility to osteoarthritis. British Journal of Sports Medicine 2011, 45(4), 278-282.
• Southam L, Panoutsopoulou K, Rayner NW, Chapman K, Durrant C, Ferreira T, Arden N, Carr A, Deloukas P, Doherty M, Loughlin J, McCaskie A, Ollier WE, Ralston S, Spector TD, Valdes AM, Wallis GA, Wilkinson JM, the arcOGEN consortium, Marchini J, Zeggini E. The effect of genome-wide association scan quality control on imputation outcome for common variants. European Journal of Human Genetics 2011, 19(5), 610–614.
• Panoutsopoulou K, Southam L, Elliott KS, Wrayner N, Zhai G, Beazley C, Thorleifsson G, Arden NK, Carr A, Chapman K, Deloukas P, Doherty M, McCaskie A, Ollier WE, Ralson SH, Spector TD, Valdes AM, Wallis GA, Wilkinson JM, Arden E, Battley K, Blackburn H, Blanco FJ, Bumpstead S, Cupples LA, Day-Williams AG, Dixon K, Doherty SA, Esko T, Evangelou E, Felson D, Gomez-Reino JJ, Gonzalez A, Gordon A, Gwilliam R, Haldorsson BV, Hauksson VB, Hofman A, Hunt SE, Ioannidis JP, Ingvarsson T, Jonsdottir I, Jonsson H, Keen R, Kerkhof HJ, Kloppenburg MG, Koller N, Lakenberg N, Lane NE, Lee AT, Metspalu A, Meulenbelt I, Nevitt MC, O'Neill F, Parimi N, Potter SC, Rego-Perez I, Riancho JA, Sherburn K, Slagboom PE, Stefansson K, Styrkarsdottir U, Sumillera M, Swift D, Thorsetinsdottir U, Tsezou A, Uitterlinkden AG, van Meurs JB, Watkins B, Wheeler M, Mitchell S, Zhu Y, Zmuda JM, arcOGEN consortium, Zeggini E, Loughlin J. Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study. Annals of the Rheumatic Diseases 2011, 70(5), 864-867.
• Evangelou E, Valdes AM, Kerkhof HJ, Styrkarsdottir U, Zhu Y, Meulenbelt I, Lories RJ, Karassa FB, Tylzanowski P, Bos SD, arcOGEN Consortium, Akune T, Arden NK, Carr A, Chapman K, Cupples LA, Dai J, Deloukas P, Doherty M, Doherty S, Engstrom G, Gonzalez A, Halldorsson BV, Hammond CL, Hart DJ, Helgadottir H, Hofman A, Ikegawa S, Ingvarsson T, Jiang Q, Jonsson H, Kaprio J, Kawaguchi H, Kisand K, Kloppenburg M, Kujala UM, Lohmander LS, Loughlin J, Luyten FP, Mabuchi A, McCaskie A, Nakajima M, Nilsson PM, Nishida N, Ollier WE, Panoutsopoulou K, van de Putte T, Ralston SH, Rivadeneira F, Saarela J, SchulteMerker S, Shi D, Slagboom PE, Sudo A, Tamm A, Tamm A, Thorleifsson G, Thorsteinsdottir U, Tsezou A, Wallis GA, Wilkinson JM, Yoshimura N, Zeggini E, Zhai G, Zhang F, Jonsdottir I, Uitterlinden AG, Felson DT, van Meurs JB, Stefansson K, Ioannidis JP, Spector TD, Translation Research in Europe Applied Technologies for Osteoarthritis (TreatOA). Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22. Annals of the Rheumatic Diseases 2011, 70(2), 349-355.
• Meulenbelt I, Bos SD, Chapman K, van der Breggen R, Houwing-Duistermaat JJ, Kremer D, Kloppenburg M, Carr A, Tsezou A, Gonzalez A, Loughlin J, Slagboom E. Meta-analyses of genes modulating intracellular T3 bio-availability reveal a possible role for the DIO3 gene in osteoarthritis susceptibility. Annals of the Rheumatic Diseases 2011, 70(1), 164-167.
• Loughlin J. Osteoarthritis year 2010 in review: genetics. Osteoarthritis and Cartilage 2011, 19(4), 342-345.
• Kerkhof HJM, Meulenbelt I, Carr A, Gonzalez A, Hart D, Hofman A, Kloppenburg M, Lane NE, Loughlin J, Nevitt MC, Pols HAP, Rivadeneira F, Slagboom EP, Spector TD, Stolk L, Tsezou A, Uitterlinden AG, Valdes AM, van Meurs JBJ. Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis. BMC Medical Genetics 2010, 11(1), 164.
• Snelling SJB, Hulley PA, Loughlin J. BMP5 activates multiple signaling pathways and promotes chondrogenic differentiation in the ATDC5 growth plate model. Growth Factors 2010, 28(4), 268-279.
• Moxley G, Meulenbelt I, Chapman K, van Duijn CM, Slagboom PE, Neale MC, Smith AJP, Carr AJ, Loughlin J. Interleukin-1 region meta-analysis with osteoarthritis phenotypes. Osteoarthritis and Cartilage 2010, 18(2), 200-207.
• Riancho JA, Garcia-Ibarbia C, Gravani A, Raine EV, Rodriguez-Fontenla C, Soto-Hermida A, Rego-Perez I, Dodd AW, Gomez-Reino JJ, Zarrabeitia MT, Garces CM, Carr A, Blanco F, Gonzalez A, Loughlin J. Common variations in estrogen-related genes are associated with severe large-joint osteoarthritis: a multicenter genetic and functional study. Osteoarthritis and Cartilage 2010, 18(7), 927-933.
• Bowl MR, Mirczuk SM, Grigorieva IV, Piret SE, Cranston T, Southam L, Allgrove J, Bahl S, Brain C, Loughlin J, Mughal Z, Ryan F, Shaw N, Thakker YV, Tiosano D, Nesbit MA, Thakker RV. Identification and characterization of novel parathyroid-specific transcription factor Glial Cells Missing Homolog B (GCMB) mutations in eight families with autosomal recessive hypoparathyroidism. Human Molecular Genetics 2010, 19(10), 2028-2038.
• Kerkhof HJM, Lories RJ, Meulenbelt I, Jonsdottir I, Valdes AM, Arp P, Ingvarsson T, Jhamai M, Jonsson H, Stolk L, Thorleifsson G, Zhai G, Zhang F, Zhu Y, van der Breggen R, Carr A, Doherty M, Doherty S, Felson DT, Gonzalez A, Halldorsson BV, Hart DJ, Hauksson VB, Hofman A, Ioannidis JPA, Kloppenburg M, Lane NE, Loughlin J, Luyten FP, Nevitt MC, Parimi N, Pols HAP, Rivadeneira F, Slagboom EP, Styrkársdóttir U, Tsezou A, van de Putte T, Zmuda J, Spector TD, Stefansson K, Uitterlinden AG, van Meurs JBJ. A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22. Arthritis & Rheumatism 2010, 62(2), 499-510.
• Wilkins JM, Southam L, Mustafa Z, Chapman K, Loughlin J. Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis. BMC Medical Genetics 2009, 10, 141.
• Egli R, Southam L, Wilkins JM, Lorenzen I, Pombo-Suarez M, Gonzalez A, Carr A, Chapman K, Loughlin J. Functional analysis of the osteoarthritis susceptibility-associated GDF5 regulatory polymorphism. Arthritis & Rheumatism 2009, 60(7), 2055-2064.
• Rodriguez-Lopez J, Pombo-Suarez M, Loughlin J, Tsezou A, Blanco FJ, Meulenbelt I, Slagboom PE, Valdes AM, Spector TD, Gomez-Reino JJ, Gonzalez A. Association of a nsSNP in ADAMTS14 to some osteoarthritis phenotypes. Osteoarthritis and Cartilage 2009, 17(3), 321-327.
• Loughlin J. Genetics and osteoarthritis: implications for the clinic. International Journal Clinical Rheumatology 2009, 4(5), 499-501.
• Meulenbelt I, Chapman K, Dieguez-Gonzalez R, Shi DQ, Tsezou A, Dai J, Malizos KN, Kloppenburg M, Carr A, Nakajima M, van der Breggen R, Lakenberg N, Gomez-Reino JJ, Jiang Q, Ikegawa S, Gonzalez A, Loughlin J, Slagboom EP. Large replication study and meta-analyses of DVWA as an osteoarthritis susceptibility locus in European and Asian populations. Human Molecular Genetics 2009, 18(8), 1518-1523.
• Evangelou E, Chapman K, Meulenbelt I, Karassa FB, Loughlin J, Carr A, Doherty M, Doherty S, Gomez-Reino JJ, Gonzalez A, Halldorsson BV, Hauksson VB, Hofman A, Hart DJ, Ikegawa S, Ingvarsson T, Jiang Q, Jonsdottir I, Jonsson H, Kerkhof HJM, Kloppenburg M, Lane NE, Li J, Lories RJ, van Meurs JBJ, Nakki A, Nevitt MC, Rodriguez-Lopez J, Shi DQ, Slagboom E, Stefansson K, Tsezou A, Wallis GA, Watson CM, Spector TD, Uitterlinden AG, Valdes AM, Ioannidis JPA. Large-Scale Analysis of Association Between GDF5 and FRZB Variants and Osteoarthritis of the Hip, Knee, and Hand. Arthritis & Rheumatism 2009, 60(6), 1710-1721.
• Dieguez-Gonzalez R, Calaza M, Shi D, Meulenbelt I, Loughlin J, Tsezou A, Dai J, Malizos KN, Slagboom EP, Kloppenburg M, Chapman K, Jiang Q, Kremer D, Gomez-Reino JJ, Nakajima N, Ikegawa S, Gonzalez A. Testing the druggable EDG2 knee OA genetic factor for replication in a wide range of sample collections. Annals of the Rheumatic Diseases 2009, 68(6), 1017-1021.
• Chapman K, Takahashi A, Meulenbelt I, Watson C, Rodriguez-Lopez J, Egli R, Tsezou A, Malizos KN, Kloppenburg M, Shi D, Southam L, Breggen Rvander, Donn R, Qin J, Doherty M, Slagboom PE, Wallis G, Kamatani N, Jiang Q, Gonzalez A, Loughlin J, Ikegawa S. A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5' UTR of GDF5 with osteoarthritis susceptibility. Human Molecular Genetics 2008, 17(10), 1497-504.
• Loughlin J, Chapman K. Big is beautiful. Osteoarthritis Cartilage 2008, 16(3), 277-278.
• Ryder JJ, Garrison K, Song F, Hooper L, Skinner J, Loke Y, Loughlin J, Higgins JP, MacGregor AJ. Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review. Annals of the Rheumatic Diseases 2008, 67(5), 584-91.
• Rodriguez-Lopez J, Mustafa Z, Pombo-Suarez M, Malizos KN, Rego I, Blanco FJ, Tsezou A, Loughlin J, Gomez-Reino JJ, Gonzalez A. Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5, in susceptibility to osteoarthritis. Arthritis & Rheumatism 2008, 58(2), 435-441.
• Valdes AM, Loughlin J, Timms KM, van Meurs JJB, Southam L, Wilson SG, Doherty S, Lories RJ, Luyten FP, Gutin A, Abkevich V, Ge D, Hofman A, Uitterlinden AG, Hart DJ, Zhang F, Zhai G, Egli RJ, Doherty M, Lanchbury J, Spector TD. Genome-wide Association Scan Identifies a Prostaglandin-Endoperoxide Synthase 2 Variant Involved in Risk of Knee Osteoarthritis. American Journal of Human Genetics 2008, 82(6), 1231-1240.
• Meulenbelt I, Min JL, Bos S, Riyazi N, Houwing-Duistermaat JJ, van der Wijk HJ, Kroon HM, Nakajima M, Ikegawa S, Uitterlinden AG, van Meurs JB, van der Deure WM , Visser TJ, Seymour AB, Lakenberg N, van der Breggen R , Kremer D, van Duijn CM, Kloppenburg M, Loughlin J, Slagboom PE. Identification of DIO2 as new susceptibility locus for symptomatic Osteoarthritis. Human Molecular Genetics 2008, 17(12), 1867-1875.
• Fresquet M, Jackson GC, Loughlin J, Briggs MD. Novel mutations in exon 2 of MATN3 affect residues within the alpha-helices of the A-domain and can result in the intracellular retention of mutant matrilin-3. Human Mutation 2008, 29(2), 330.
• Snelling S, Ferreira A, Loughlin J. Allelic expression analysis suggests that cis-acting polymorphism of FRZB expression does not contribute to osteoarthritis susceptibility. Osteoarthritis and Cartilage 2007, 15(1), 90-92.
• Southam L, Rodriguez-Lopez J, Wilkins JM, Pombo-Suarez M, Snelling S, Gomez-Reino JJ, Chapman K, Gonzalez A, Loughlin J. An SNP in the 5'-UTR of GDF5 is associated with osteoarthritis susceptibility in Europeans and with in vivo differences in allelic expression in articular cartilage. Human Molecular Genetics 2007, 16(18), 2226-2232.
• Wilkins JM, Southam L, Price AJ, Mustafa Z, Carr A, Loughlin J. Extreme context specificity in differential allelic expression. Hum Mol Genet 2007, 16(5), 537-546.
• Snelling S, Sinsheimer JS, Carr A, Loughlin J. Genetic association analysis of LRCH1 as an osteoarthritis susceptibility locus. Rheumatology 2007, 46(2), 250-252.
• Loughlin J, Meulenbelt I, Min J, Mustafa Z, Sinsheimer JS, Carr A, Slagboom PE. Genetic association analysis of RHOB and TXNDC3 in osteoarthritis. American Journal of Human Genetics 2007, 80(2), 383-386; author reply 386-387.
• Nakamura T, Shi D, Tzetis M, Rodriguez-Lopez J, Miyamoto Y, Tsezou A, Gonzalez A, Jiang Q, Kamatani N, Loughlin J, Ikegawa S. Meta-analysis of association between the ASPN D-repeat and osteoarthritis. Human Molecular Genetics 2007, 16(14), 1676-81.
• Wilkins JM, Loughlin J, Snelling SJB. Osteoarthritis genetics: current status and future prospects. Future Rheumatology 2007, 2(6), 607-620.
• Valdes AM, Loughlin J, Oene MV, Chapman K, Surdulescu GL, Doherty M, Spector TD. Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee. Arthritis Rheum 2007, 56(1), 137-146.
• Gordon A, Southam L, Loughlin J, Wilson AG, Stockley I, Hamer AJ, Eastell R, Wilkinson JM. Variation in the secreted frizzled-related protein-3 gene and risk of Osteolysis and heterotopic ossification after total hip arthroplasty. Journal of Orthopaedic Research 2007, 25(12), 1665-1670.
• Southam L, Heath O, Chapman K, Loughlin J. Association analysis of the interleukin 17 genes IL17A and IL17F as potential osteoarthritis susceptibility loci. Annals of the Rheumatic Diseases 2006, 65(4), 556-557.
• Chapman K, Loughlin J. Association of the interleukin-1 gene cluster with osteoarthritis of the hip: comment on the article by Meulenbelt et al and the letter by Smith et al. Arthritis & Rheumatism 2006, 54(11), 3722-3723.
• Loughlin J. Osteoarthritis linkage scan: more loci for the geneticists to investigate. Annals of the Rheumatic Diseases 2006, 65(10), 1265-6.
• Chapman K, Carr A, Loughlin J, Sinsheimer JS. Presence of a primary hip osteoarthritis susceptibility locus on chromosome 6: comment on the article by Meenagh et al. Arthritis Rheum 2006, 54(3), 1026-1027.
• Valdes AM, van Oene M, Hart DJ, Surdulescu GL, Loughlin J, Doherty M, Spector TD. Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women. Arthritis & Rheumatism 2006, 54(2), 533-539.
• Loughlin J, Sinsheimer JS, Carr A, Chapman K. The CALM1 core promoter polymorphism is not associated with hip osteoarthritis in a United Kingdom Caucasian population. Osteoarthritis Cartilage 2006, 14(3), 295-298.
• Loughlin J. Crystals in hand. Arthritis Research & Therapy 2005, 7(5), 187-188.
• Kawahara C, Forster T, Chapman K, Carr A, Loughlin J. Genetic association analysis of the IGFBP7, ADAMTS3, and IL8 genes as the potential osteoarthritis susceptibility that maps to chromosome 4q. Annals of the Rheumatic Diseases 2005, 64(3), 474-476.
• Spencer JM, Loughlin J, Clipsham K, Carr AJ. Genetic background increases the risk of hip osteoarthritis. Clinical Orthopaedics and Related Research 2005, (431), 134-137.
• Mustafa Z, Dowling B, Chapman K, Sinsheimer JS, Carr A, Loughlin J. Investigating the aspartic acid (D) repeat of asporin as a risk factor for osteoarthritis in a UK Caucasian population. Arthritis & Rheumatism 2005, 52(11), 3502-3506.
• Loughlin J. Polymorphism in signal transduction is a major route through which osteoarthritis susceptibility is acting. Current Opinion in Rheumatology 2005, 17(5), 629-633.
• Peach CA, Carr AJ, Loughlin J. Recent advances in the genetic investigation of osteoarthritis. Trends in Molecular Medicine 2005, 11(4), 186-191.
• Loughlin J, Carr A, Chapman K. The common HFE variants C282Y and H63D are not associated with primary OA of the hip or knee. Journal of Rheumatology 2005, 32(2), 391-2; author reply 392.
• Loughlin J. The genetic epidemiology of human primary osteoarthritis: current status. Expert Reviews in Molecular Medicine 2005, 7(9), 1-12.
• Forster T, Chapman K, Loughlin J. Common variants within the interleukin 4 receptor alpha gene (IL4R) are associated with susceptibility to osteoarthritis. Human Genetics 2004, 114(4), 391-395.
• Loughlin J. Familial inheritance of osteoarthritis: documented family subsets. Clinical Orthopaedics and Related Research 2004, 427(supplement), S22-25.
• Forster T, Chapman K, Marcelline L, Mustafa Z, Southam L, Loughlin J. Finer linkage mapping of primary osteoarthritis susceptibility loci on chromosomes 4 and 16 in families with affected women. Arthritis & Rheumatism 2004, 50(1), 98-102.
• Loughlin J, Dowling B, Chapman K, Marcelline L, Mustafa Z, Southam L, Ferreira A, Ciesielski C, Carson DA, Corr M. Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proceedings of the National Academy of Sciences of the United States of America 2004, 101(26), 9757-9762.
• Southam L, Dowling B, Ferreira A, Marcelline L, Mustafa Z, Chapman K, Bentham G, Carr A, Loughlin J. Microsatellite association mapping of a primary osteoarthritis susceptibility locus on chromosome 6p12.3-q13. Arthritis & Rheumatism 2004, 50(12), 3910-3914.
• Bergink AP, van Meurs JB, Loughlin J, Arp PP, Fang Y, Hofman A, van Leeuwen JP, van Duijn CM, Uitterlinden AG, Pols HA. Estrogen receptor alpha gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women. Arthritis & Rheumatism 2003, 48(7), 1913-1922.
• Southam L, Chapman K, Loughlin J. Genetic association analysis of BMP5 as a potential osteoarthritis susceptibility gene. Rheumatology 2003, 42(7), 911-912.
• Loughlin J. Genetics of osteoarthritis and potential for drug development. Current Opinion in Pharmacology 2003, 3(3), 295-299.
• Nentwich HA, Mustafa Z, Rugg MS, Marsden BD, Cordell MR, Mahoney DJ, Jenkins SC, Dowling B, Fries E, Milner CM, Loughlin J, Day AJ. A novel allelic variant of the human TSG-6 gene encoding an amino acid difference in the CUB module. Chromosomal localization, frequency analysis, modeling, and expression. Journal of Biological Chemistry 2002, 277(18), 15354-15362.
• Loughlin J, Dowling B, Mustafa Z, Chapman K. Association of the interleukin-1 gene cluster on chromosome 2q13 with knee osteoarthritis. Arthritis & Rheumatism 2002, 46(6), 1519-1527.
• Loughlin J, Mustafa Z, Dowling B, Southam L, Marcelline L, Raina SS, Ala-Kokko L, Chapman K. Finer linkage mapping of a primary hip osteoarthritis susceptibility locus on chromosome 6. European Journal of Human Genetics 2002, 10(9), 562-568.
• Chapman K, Mustafa Z, Dowling B, Southam L, Carr A, Loughlin J. Finer linkage mapping of primary hip osteoarthritis susceptibility on chromosome 11q in a cohort of affected female sibling pairs. Arthritis & Rheumatism 2002, 46(7), 1780-1783.
• Loughlin J. Genome studies and linkage in primary osteoarthritis. Rheumatic Disease Clinics of North America 2002, 28(1), 95-109.
• Loughlin J, Dowling B, Mustafa Z, Southam L, Chapman K. Refined linkage mapping of a hip osteoarthritis susceptibility locus on chromosome 2q. Rheumatology 2002, 41(8), 955-956.
• Loughlin J. Genetic epidemiology of primary osteoarthritis. Current Opinion in Rheumatology 2001, 13(2), 111-116.
• Chapman KL, Mortier GR, Chapman K, Loughlin J, Grant ME, Briggs MD. Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia. Nature Genetics 2001, 28(4), 393-396.
• Loughlin J, Dowling B, Mustafa Z, Smith A, Sykes B, Chapman K. Analysis of the association of the matrillin-1 gene (CRTM) with osteoarthritis: comment on the article by Meulenbelt et al. Arthritis Rheum 2000, 43(6), 1423-1425.
• Loughlin J, Sinsheimer JS, Mustafa Z, Carr AJ, Clipsham K, Bloomfield VA, Chitnavis J, Bailey A, Sykes B, Chapman K. Association analysis of the vitamin D receptor gene, the type I collagen gene COL1A1, and the estrogen receptor gene in idiopathic osteoarthritis. Journal of Rheumatology 2000, 27(3), 779-784.
• Henderson S, Sillence D, Loughlin J, Bennetts B, Sykes B. Germline and somatic mosaicism in achondroplasia. Journal of Medical Genetics 2000, 37(12), 956-958.
• Mustafa Z, Chapman K, Irven C, Carr AJ, Clipsham K, Chitnavis J, Sinsheimer JS, Bloomfield VA, McCartney M, Cox O, Sykes B, Loughlin J. Linkage analysis of candidate genes as susceptibility loci for osteoarthritis-suggestive linkage of COL9A1 to female hip osteoarthritis. Rheumatology 2000, 39(3), 299-306.
• Loughlin J, Mustafa Z, Smith A, Irven C, Carr AJ, Clipsham K, Chitnavis J, Bloomfield VA, McCartney M, Cox O, Sinsheimer JS, Sykes B, Chapman KE. Linkage analysis of chromosome 2q in osteoarthritis. Rheumatology 2000, 39(4), 377-381.
• Oldridge M, Temple IK, Santos HG, Gibbons RJ, Mustafa Z, Chapman KE, Loughlin J, Wilkie AO. Brachydactyly Type B: Linkage to Chromosome 9q22 and Evidence for Genetic Heterogeneity. American Journal of Human Genetics 1999, 64(2), 578-585.
• Chapman K, Mustafa Z, Irven C, Carr AJ, Clipsham K, Smith A, Chitnavis J, Sinsheimer JS, Bloomfield VA, McCartney M, Cox O, Cardon LR, Sykes B, Loughlin J. Osteoarthritis-susceptibility locus on chromosome 11q, detected by linkage. American Journal of Human Genetics 1999, 65(1), 167-174.
• Holden P, Canty EG, Mortier GR, Zabel B, Spranger J, Carr A, Grant ME, Loughlin JA, Briggs MD. Identification of novel pro-alpha 2(IX) collagen gene mutations in two families with distinctive olgo-epiphyseal forms of multiple epiphyseal dysplasia. American Journal of Human Genetics 1999, 65(1), 31-38.
• Loughlin J, Mustafa Z, Irven C, Smith A, Carr AJ, Sykes B, Chapman K. Stratification analysis of an osteoarthritis genome screen-suggestive linkage to chromosomes 4, 6, and 16. American Journal of Human Genetics 1999, 65(6), 1795-1798.
• M. E. Hurles,C. Irven,J. Nicholson,P. G. Taylor,F. R. Santos,J. Loughlin,M. A. Jobling,B. C. Sykes. European Y-chromosomal lineages in Polynesians: a contrast to the population structure revealed by mtDNA. Am J Hum Genet 1998, 63(6), 1793-806.
• J. Loughlin,C. Irven,Z. Mustafa,M. D. Briggs,A. Carr,S. A. Lynch,R. G. Knowlton,D. H. Cohn,B. Sykes. Identification of five novel mutations in cartilage oligomeric matrix protein gene in pseudoachondroplasia and multiple epiphyseal dysplasia. Hum Mutat 1998, Suppl 1, S10-7.
• D. J. Wilkin,J. K. Szabo,R. Cameron,S. Henderson,G. A. Bellus,M. L. Mack,I. Kaitila,J. Loughlin,A. Munnich,B. Sykes,J. Bonaventure,C. A. Francomano. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Am J Hum Genet 1998, 63(3), 711-6.
• J. Chitnavis,J. S. Sinsheimer,K. Clipsham,J. Loughlin,B. Sykes,P. D. Burge,A. J. Carr. Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis. J Bone Joint Surg Br 1997, 79(4), 660-4.
• Spector TD, Cicuttini F, Baker J, Loughlin J, Hart D. Genetic influences on osteoarthritis in women: a twin study. British Medical Journal 1996, 312(7036), 940-943.
• J. Loughlin,C. Irven,N. Athanasou,A. Carr,B. Sykes. Differential allelic expression of the type II collagen gene (COL2A1) in osteoarthritic cartilage. Am J Hum Genet 1995, 56(5), 1186-93.
• J. Loughlin,C. Irven,L. J. Hardwick,S. Butcher,S. Walsh,P. Wordsworth,B. Sykes. Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II). Hum Mol Genet 1995, 4(9), 1649-51.
• J. Loughlin,C. Irven,B. Sykes. Exclusion of the cartilage link protein and the cartilage matrix protein genes as the mutant loci in several heritable chondrodysplasias. Hum Genet 1994, 94(6), 698-700.
• M. D. Briggs,H. Choi,M. L. Warman,J. A. Loughlin,P. Wordsworth,B. C. Sykes,C. M. Irven,M. Smith,R. Wynne-Davies,M. H. Lipson,et al. Genetic mapping of a locus for multiple epiphyseal dysplasia (EDM2) to a region of chromosome 1 containing a type IX collagen gene. Am J Hum Genet 1994, 55(4), 678-84.
• A. S. Virdi,J. A. Loughlin,C. M. Irven,J. Goodship,B. C. Sykes. Mutation screening by a combination of biotin-SSCP and direct sequencing. Hum Genet 1994, 93(3), 287-90.
• J. Loughlin,C. Irven,C. Fergusson,B. Sykes. Sibling pair analysis shows no linkage of generalized osteoarthritis to the loci encoding type II collagen, cartilage link protein or cartilage matrix protein. Br J Rheumatol 1994, 33(12), 1103-6.