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18. Scanning horizons in research, policy and practice

Author

Sutherland, WJ, Brotherton, P, Davies, Z, Pettorelli, N, Vira, B, Vickery, J, Wintle, B, Kennicutt II, MC, Sutherland, WJ, Brotherton, P, Davies, Z, Pettorelli, N, Vira, B, Vickery, J, Wintle, B, and Kennicutt II, MC

Abstract

New and emerging environmental issues make policy and practice difficult. A pressing need to respond when knowledge of the problem is limited is added to an already challenging conservation agenda. Horizon-scanning is an evolving approach that draws on diverse information sources to identify early indications of poorly recognised threats and opportunities. There are many ways to conduct horizon scans, ranging from automated techniques that scan online content and mine text to manual methods that systematically consult large groups of people (often experts). These different approaches aim to sort through vast volumes of information to look for signals of change, for example the rise in microplastics or the use of mobile phones to gather data in remote forests. Identifying these new threats and opportunities is the first important step towards further researching and managing them. This chapter reviews different approaches to horizon-scanning, together with ways of encouraging uptake of scanning outputs. It concludes by introducing emerging technologies that will add value to horizon-scanning in the future.

Published
2020

31. Where are commodity crops certified, and what does it mean for conservation and poverty alleviation?

Author

Tayleur, C, Balmford, A, Buchanan, GM, Butchart, SHM, Corlet Walker, C, Ducharme, H, Green, RE, Milder, JC, Sanderson, FJ, Thomas, DHL, Tracewski, L, Vickery, J, Phalan, B, Green, RE [0000-0001-8690-8914], and Apollo - University of Cambridge Repository

Subjects
Governance, Fair trade, Tropical commodities, Voluntary sustainability standards, Agricultural certification, Eco-labeling
Abstract

Voluntary sustainability standards have expanded dramatically over the last decade. In the agricultural sector, such standards aim to ensure environmentally and socially sustainable production of a variety of commodity crops. However, little is known about where agricultural certification operates and whether certified lands are best located for conserving the world's most important biodiversity and benefiting the most vulnerable producers. To examine these questions we developed the first global map of commodity crop certification, synthesizing data from over one million farms to reveal the distribution of certification in unprecedented detail. It highlights both geographical clusters of certification as well as spatial bias in the location of certification with respect to environmental, livelihood and physical variables. Excluding organic certification, for which spatial data were not available, most certification of commodity crops is in tropical regions. Certification appears to be concentrated in areas important for biodiversity conservation, but not in those areas most in need of poverty alleviation, although there were exceptions to each of these patterns. We argue that the impact of sustainability standards could be increased by identifying places where it would be most beneficial to strengthen, consolidate, and expand certification. To achieve this, standards organizations will need to undertake more rigorous collection of spatial data, and more detailed analysis of their existing reach and impacts, with attention to potential trade-offs between different objectives. Efforts to promote spatial prioritization will require new partnerships to align specific conservation aims with the interests and capabilities of farmers.

Published
2018

33. Balance Right in Multiple Sclerosis (BRiMS): Preliminary results of a randomised controlled feasibility trial

Author

Gunn, H., primary, Andrade, J., additional, Paul, L., additional, Miller, L., additional, Stevens, K., additional, Creanor, S., additional, Green, C., additional, Ewings, P., additional, Barton, A., additional, Berrow, M., additional, Vickery, J., additional, Marshall, B., additional, Marsden, J., additional, and Freeman, J., additional

Published
2019
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36. A preconsultation web-based tool to generate an agenda for discussion in diabetes outpatient clinics to improve patient outcomes (DIAT): a feasibility study

Author

Ukoumunne, OC, Vaidya, B, Frost, J, Anderson, R, Argyle, C, Daly, M, Harris-Golesworthy, F, Harris, J, Gibson, A, Ingram, W, Pinkney, J, Vickery, J, Britten, N, Ukoumunne, OC, Vaidya, B, Frost, J, Anderson, R, Argyle, C, Daly, M, Harris-Golesworthy, F, Harris, J, Gibson, A, Ingram, W, Pinkney, J, Vickery, J, and Britten, N

Abstract

OBJECTIVE: To test the feasibility of running a randomised controlled trial of a preconsultation web-based intervention (Presenting Asking Checking Expressing (PACE-D)) to improve the quality of care and clinical outcomes in patients with diabetes. DESIGN AND SETTING: A feasibility study (with randomisation) conducted at outpatient diabetes clinics at two secondary care hospitals in Devon, UK. PARTICIPANTS: People with diabetes (type 1 and type 2) attending secondary care general diabetes outpatient clinics. INTERVENTION: The PACE-D, a web-based tool adapted for patients with diabetes to use before their consultation to generate an agenda of topics to discuss with their diabetologist. OUTCOMES: The percentage of eligible patients who were recruited and the percentage of participants for whom routine glycosylated haemoglobin (HbA1c) data (the putative primary outcome) could be extracted from medical notes and who completed secondary outcome assessments via questionnaire at follow-up were reported. RESULTS: In contrast with the planned recruitment of 120 participants, only 71 participants were randomised during the 7-month recruitment period. This comprised 18.7% (95% CI 14.9% to 23.0%) of those who were eligible. Mean (SD) age of the participants was 56.5 (12.4) years and 66.2% had type 1 diabetes. Thirty-eight patients were randomised to the intervention arm and 33 to the control arm. HbA1c data were available for only 73% (95% CI 61% to 83%) of participants at the 6 months follow-up. The questionnaire-based data were collected for 66% (95% CI 54% to 77%) of the participants at 6 months follow-up. Participants reported that the PACE-D tool was easy to use. CONCLUSIONS: A randomised controlled trial of the preconsultation web-based intervention as set out in our current protocol is not feasible without significant modification to improve recruitment and follow-up of participants. The study also provides insights into the feasibility and challenges of conducting compl

Published
2017

38. Balance Right in Multiple Sclerosis (BRiMS): a guided self-management programme to reduce falls and improve quality of life, balance and mobility in people with secondary progressive multiple sclerosis: a protocol for a feasibility randomised controlled trial

Author

Gunn, H., primary, Andrade, J., additional, Paul, L., additional, Miller, L., additional, Creanor, S., additional, Green, C., additional, Marsden, J., additional, Ewings, P., additional, Berrow, M., additional, Vickery, J., additional, Barton, A., additional, Marshall, B., additional, Zajicek, J., additional, and Freeman, J. A., additional

Published
2017
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39. The influence of mixing temperature and powder/liquid ratio on the film thickness of three glass-ionomer cements.

Author

Brackett, William W., Vickery, Jeannie M., Brackett, W W, and Vickery, J M

Subjects
TEMPERATURE, DENTAL cements, IONOMERS, GLASS, DENTAL materials, DENTAL technology, DENTAL equipment, BIOMEDICAL materials, DENTISTRY
Abstract

Three glass-ionomer cements, mixed at room temperature and cold mixed, were evaluated for film thickness at different powder to liquid ratios. Film thickness was measured at 1, 2, and 3 minutes after mixing was initiated. The relative accuracy of the manufacturer's volumetric dispensing systems was also measured. For two of the three cements tested, cold mixing significantly reduced film thickness at extended working times and increased powder/liquid ratios. The results suggest that the appearance of the cement surface indicates setting in advance of film thickness and that cold mixing should be routinely employed. [ABSTRACT FROM AUTHOR]

Published
1994

42. MBS ratings and the mortgage credit boom

Author

Ashcraft, A., Goldsmith-Pinkham, P., Vickery, J., and Department of Finance

Subjects
Credit rating agencies, G24, mortgages, subprime crisis, ddc:330, Mortgage-Backed Securities, G21, G01, Credit Rating Agencies, Subprime Crisis, mortgage-backed securities
Abstract

We study credit ratings on subprime and Alt-A mortgage-backed securities (MBS) deals issued between 2001 and 2007, the period leading up to the subprime crisis. The fraction of highly-rated securities in each deal is decreasing in mortgage credit risk (measured either ex-ante or ex-post), suggesting ratings contain useful information for investors. However, we also find evidence of significant time-variation in risk-adjusted credit ratings, including a progressive decline in standards around the MBS market peak between the start of 2005 and mid-2007. Conditional on initial ratings, we observe underperformance (high mortgage defaults and losses, and large rating downgrades) amongst deals with observably higher-risk mortgages based on a simple ex-ante model, and deals with a high fraction of opaque low-documentation loans. These findings hold over the entire sample period, not just for deal cohorts most affected by the crisis.

Published
2010

43. NOU seminar: Birds of agricultural areas / Nederlandse Ornithologische Unie: themadag 'vogels van het agrarisch gebied'

Author

Bijlsma, R., Kleijn, D., Koffijberg, K., Teunissen, W., Kragten, S., Oosterveld, E., Schekkerman, H., and Vickery, J.

Subjects
populatiedichtheid, wildbescherming, WIMEK, bedreigde soorten, Plant Ecology and Nature Conservation, endangered species, Centrum Ecosystemen, Centre for Ecosystem Studies, birds, wildlife conservation, Plantenecologie en Natuurbeheer, vogels, Wageningen Environmental Research, population density
Abstract

Het gaat bijzonder slecht met veel vogels van het agrarisch gebied. Zowel weidevogels als akkervogels staan zwaar onder druk. Vogelbescherming Nederland, SOVON en de Ornothologische Unie hielden een studiedag in Leiden (maart 2006). Dit artikel doet verslag van (onderzoeks)bevindingen vanuit CML, SOVON, Alterra, Radboud Universiteit en Altenburg & Wymenga

Published
2006

47. A pilot randomised controlled trial of a preconsultation web- based intervention to improve the care quality and clinical outcomes of diabetes outpatients (DIAT)

Author

Frost, J, Anderson, R, Argyle, C, Daly, M, Harris-Golesworthy, F, Harris, J, Gibson, A, Ingram, W, Pinkney, J, Ukoumunne, OC, Vaidya, B, Vickery, J, Britten, N, Frost, J, Anderson, R, Argyle, C, Daly, M, Harris-Golesworthy, F, Harris, J, Gibson, A, Ingram, W, Pinkney, J, Ukoumunne, OC, Vaidya, B, Vickery, J, and Britten, N

Abstract

INTRODUCTION: Diabetes is a chronic condition associated with many long-term complications. People with diabetes need to actively manage their condition, which can be complex. In consultations with healthcare professionals, patients receive advice about their diabetes but do not always discuss things which concern them, perhaps because of the perceived limited time or embarrassment. We want to test a 'preconsultation' intervention in which the patient is supported by a healthcare assistant to complete a web-based intervention aimed at producing an agenda to help them identify important areas for discussion in the consultation. Use of this agenda may enable the patient to play a more active role in that consultation and consequently become more confident, and hence more successful, in managing their condition. METHODS AND ANALYSIS: In this pilot randomised controlled trial, 120 people with diabetes will be randomised with equal allocation to receive the intervention or usual clinical care. The primary outcome is reduction in glycosylated haemoglobin(HbA1c). Secondary outcomes are patient-reported communication, enablement, self-care activity, diabetes-dependent quality of life, empowerment, satisfaction, health-related quality of life and resource use. The aim of the pilot study was to estimate parameters to inform the design of the definitive trial. Follow-up on quantitative outcomes will be at 3 and 6 months. A nested qualitative study will collect data on the patients' experiences of producing an agenda. Resource use data and medication use will also be collected via a review of medical records for a sample of participants. ETHICS AND DISSEMINATION: Approval was granted by the NHS Research Ethics Committee North West-Preston (13/NW/0123). Dissemination will include publication of quantitative and qualitative findings, and experience of public involvement in peer-reviewed journals. Results will also be disseminated to trial participants via workshops led by lay coa

Published
2013

49. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Author

Sawcer, S., Hellenthal, G., Pirinen, M., Spencer, C.C.A., Patsopoulos, N.A., Moutsianas, L., Dilthey, A., Su, Z., Freeman, C., Hunt, S.E., Edkins, S., Gray, E., Booth, D.R., Potter, S.C., Goris, A., Band, G., Bang Oturai, A., Strange, A., Saarela, J., Bellenguez, C., Fontaine, B., Gillman, M., Hemmer, B., Gwilliam, R., Zipp, F., Jayakumar, A., Martin, R., Leslie, S., Hawkins, S., Giannoulatou, E., D’alfonso, S., Blackburn, H., Martinelli Boneschi, F., Liddle, J., Harbo, H.F., Perez, M.L., Spurkland, A., Waller, M.J., Mycko, M.P., Ricketts, M., Comabella, M., Hammond, N., Kockum, I., McCann, O.T., Ban, M., Whittaker, P., Kemppinen, A., Weston, P., Hawkins, C., Widaa, S., Zajicek, J., Dronov, S., Robertson, N., Bumpstead, S.J., Barcellos, L.F., Ravindrarajah, R., Abraham, R., Alfredsson, L., Ardlie, K., Aubin, C., Baker, A., Baker, K., Baranzini, S.E., Bergamaschi, L., Bergamaschi, R., Bernstein, A., Berthele, A., Boggild, M., Bradfield, J.P., Brassat, D., Broadley, S.A., Buck, D., Butzkueven, H., Capra, R., Carroll, W.M., Cavalla, P., Celius, E.G., Cepok, S., Chiavacci, R., Clerget-Darpoux, F., Clysters, K., Comi, G., Cossburn, M., Cournu-Rebeix, I., Cox, M.B., Cozen, W., Cree, B.A.C., Cross, A.H., Cusi, D., Daly, M.J., Davis, E., de Bakker, P.I.W., Debouverie, M., D’hooghe, M.B., Dixon, K., Dobosi, R., Dubois, B., Ellinghaus, D., Elovaara, I., Esposito, F., Fontenille, C., Foote, S., Franke, A., Galimberti, D., Ghezzi, A., Glessner, J., Gomez, R., Gout, O., Graham, C., Grant, S.F.A., Rosa Guerini, F., Hakonarson, H., Hall, P., Hamsten, A., Hartung, H-P, Heard, R.N., Heath, S., Hobart, J., Hoshi, M., Infante-Duarte, C., Ingram, G., Ingram, W., Islam, T., Jagodic, M., Kabesch, M., Kermode, A.G., Kilpatrick, T.J., Kim, C., Klopp, N., Koivisto, K., Larsson, M., Lathrop, M., Lechner-Scott, J.S., Leone, M.A., Leppä, V., Liljedahl, U., Lima Bomfim, I., Lincoln, R.R., Link, J., Liu, J., Lorentzen, Å.R., Lupoli, S., Macciardi, F., Mack, T., Marriott, M., Martinelli, V., Mason, D., McCauley, J.L., Mentch, F., Mero, I-L, Mihalova, T., Montalban, X., Mottershead, J., Myhr, K-M, Naldi, P., Ollier, W., Page, A., Palotie, A., Pelletier, J., Piccio, L., Pickersgill, T., Piehl, F., Pobywajlo, S., Quach, H.L., Ramsay, P.P., Reunanen, M., Reynolds, R., Rioux, J.D., Rodegher, M., Roesner, S., Rubio, J.P., Rückert, I-M, Salvetti, M., Salvi, E., Santaniello, A., Schaefer, C.A., Schreiber, S., Schulze, C., Scott, R.J., Sellebjerg, F., Selmaj, K.W., Sexton, D., Shen, L., Simms-Acuna, B., Skidmore, S., Sleiman, P.M.A., Smestad, C., Sørensen, P.S., Søndergaard, H.B., Stankovich, J., Strange, R.C., Sulonen, A-M, Sundqvist, E., Syvänen, A-C, Taddeo, F., Taylor, B., Blackwell, J.M., Tienari, P., Bramon, E., Tourbah, A., Brown, M.A., Tronczynska, E., Casas, J.P., Tubridy, N., Corvin, A., Vickery, J., Jankowski, J., Villoslada, P., Markus, H.S., Wang, K., Mathew, C.G., Wason, J., Palmer, C.N.A., Wichmann, H-E, Plomin, R., Willoughby, E., Rautanen, A., Winkelmann, J., Wittig, M., Trembath, R.C., Yaouanq, J., Viswanathan, A.C., Zhang, H., Wood, N.W., Zuvich, R., Deloukas, P., Langford, C., Duncanson, A., Oksenberg, J.R., Pericak-Vance, M.A., Haines, J.L., Olsson, T., Hillert, J., Ivinson, A.J., De Jager, P.L., Peltonen, L., Stewart, G.J., Hafler, D.A., Hauser, S.L., McVean, G., Donnelly, P., Compston, A., Sawcer, S., Hellenthal, G., Pirinen, M., Spencer, C.C.A., Patsopoulos, N.A., Moutsianas, L., Dilthey, A., Su, Z., Freeman, C., Hunt, S.E., Edkins, S., Gray, E., Booth, D.R., Potter, S.C., Goris, A., Band, G., Bang Oturai, A., Strange, A., Saarela, J., Bellenguez, C., Fontaine, B., Gillman, M., Hemmer, B., Gwilliam, R., Zipp, F., Jayakumar, A., Martin, R., Leslie, S., Hawkins, S., Giannoulatou, E., D’alfonso, S., Blackburn, H., Martinelli Boneschi, F., Liddle, J., Harbo, H.F., Perez, M.L., Spurkland, A., Waller, M.J., Mycko, M.P., Ricketts, M., Comabella, M., Hammond, N., Kockum, I., McCann, O.T., Ban, M., Whittaker, P., Kemppinen, A., Weston, P., Hawkins, C., Widaa, S., Zajicek, J., Dronov, S., Robertson, N., Bumpstead, S.J., Barcellos, L.F., Ravindrarajah, R., Abraham, R., Alfredsson, L., Ardlie, K., Aubin, C., Baker, A., Baker, K., Baranzini, S.E., Bergamaschi, L., Bergamaschi, R., Bernstein, A., Berthele, A., Boggild, M., Bradfield, J.P., Brassat, D., Broadley, S.A., Buck, D., Butzkueven, H., Capra, R., Carroll, W.M., Cavalla, P., Celius, E.G., Cepok, S., Chiavacci, R., Clerget-Darpoux, F., Clysters, K., Comi, G., Cossburn, M., Cournu-Rebeix, I., Cox, M.B., Cozen, W., Cree, B.A.C., Cross, A.H., Cusi, D., Daly, M.J., Davis, E., de Bakker, P.I.W., Debouverie, M., D’hooghe, M.B., Dixon, K., Dobosi, R., Dubois, B., Ellinghaus, D., Elovaara, I., Esposito, F., Fontenille, C., Foote, S., Franke, A., Galimberti, D., Ghezzi, A., Glessner, J., Gomez, R., Gout, O., Graham, C., Grant, S.F.A., Rosa Guerini, F., Hakonarson, H., Hall, P., Hamsten, A., Hartung, H-P, Heard, R.N., Heath, S., Hobart, J., Hoshi, M., Infante-Duarte, C., Ingram, G., Ingram, W., Islam, T., Jagodic, M., Kabesch, M., Kermode, A.G., Kilpatrick, T.J., Kim, C., Klopp, N., Koivisto, K., Larsson, M., Lathrop, M., Lechner-Scott, J.S., Leone, M.A., Leppä, V., Liljedahl, U., Lima Bomfim, I., Lincoln, R.R., Link, J., Liu, J., Lorentzen, Å.R., Lupoli, S., Macciardi, F., Mack, T., Marriott, M., Martinelli, V., Mason, D., McCauley, J.L., Mentch, F., Mero, I-L, Mihalova, T., Montalban, X., Mottershead, J., Myhr, K-M, Naldi, P., Ollier, W., Page, A., Palotie, A., Pelletier, J., Piccio, L., Pickersgill, T., Piehl, F., Pobywajlo, S., Quach, H.L., Ramsay, P.P., Reunanen, M., Reynolds, R., Rioux, J.D., Rodegher, M., Roesner, S., Rubio, J.P., Rückert, I-M, Salvetti, M., Salvi, E., Santaniello, A., Schaefer, C.A., Schreiber, S., Schulze, C., Scott, R.J., Sellebjerg, F., Selmaj, K.W., Sexton, D., Shen, L., Simms-Acuna, B., Skidmore, S., Sleiman, P.M.A., Smestad, C., Sørensen, P.S., Søndergaard, H.B., Stankovich, J., Strange, R.C., Sulonen, A-M, Sundqvist, E., Syvänen, A-C, Taddeo, F., Taylor, B., Blackwell, J.M., Tienari, P., Bramon, E., Tourbah, A., Brown, M.A., Tronczynska, E., Casas, J.P., Tubridy, N., Corvin, A., Vickery, J., Jankowski, J., Villoslada, P., Markus, H.S., Wang, K., Mathew, C.G., Wason, J., Palmer, C.N.A., Wichmann, H-E, Plomin, R., Willoughby, E., Rautanen, A., Winkelmann, J., Wittig, M., Trembath, R.C., Yaouanq, J., Viswanathan, A.C., Zhang, H., Wood, N.W., Zuvich, R., Deloukas, P., Langford, C., Duncanson, A., Oksenberg, J.R., Pericak-Vance, M.A., Haines, J.L., Olsson, T., Hillert, J., Ivinson, A.J., De Jager, P.L., Peltonen, L., Stewart, G.J., Hafler, D.A., Hauser, S.L., McVean, G., Donnelly, P., and Compston, A.

Abstract

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability1. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals2, 3, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk4. Modestly powered genome-wide association studies (GWAS)5, 6, 7, 8, 9, 10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility11. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

Published
2011

50. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Author

Sawcer, S, Hellenthal, G, Pirinen, M, Spencer, CCA, Patsopoulos, NA, Moutsianas, L, Dilthey, A, Su, Z, Freeman, C, Hunt, SE, Edkins, S, Gray, E, Booth, DR, Potter, SC, Goris, A, Band, G, Oturai, AB, Strange, A, Saarela, J, Bellenguez, C, Fontaine, B, Gillman, M, Hemmer, B, Gwilliam, R, Zipp, F, Jayakumar, A, Martin, R, Leslie, S, Hawkins, S, Giannoulatou, E, D'alfonso, S, Blackburn, H, Boneschi, FM, Liddle, J, Harbo, HF, Perez, ML, Spurkland, A, Waller, MJ, Mycko, MP, Ricketts, M, Comabella, M, Hammond, N, Kockum, I, McCann, OT, Ban, M, Whittaker, P, Kemppinen, A, Weston, P, Hawkins, C, Widaa, S, Zajicek, J, Dronov, S, Robertson, N, Bumpstead, SJ, Barcellos, LF, Ravindrarajah, R, Abraham, R, Alfredsson, L, Ardlie, K, Aubin, C, Baker, A, Baker, K, Baranzini, SE, Bergamaschi, L, Bergamaschi, R, Bernstein, A, Berthele, A, Boggild, M, Bradfield, JP, Brassat, D, Broadley, SA, Buck, D, Butzkueven, H, Capra, R, Carroll, WM, Cavalla, P, Celius, EG, Cepok, S, Chiavacci, R, Clerget-Darpoux, F, Clysters, K, Comi, G, Cossburn, M, Cournu-Rebeix, I, Cox, MB, Cozen, W, Cree, BAC, Cross, AH, Cusi, D, Daly, MJ, Davis, E, de Bakker, PIW, Debouverie, M, D'hooghe, MB, Dixon, K, Dobosi, R, Dubois, B, Ellinghaus, D, Elovaara, I, Esposito, F, Fontenille, C, Foote, S, Franke, A, Galimberti, D, Ghezzi, A, Glessner, J, Gomez, R, Gout, O, Graham, C, Grant, SFA, Guerini, FR, Hakonarson, H, Hall, P, Hamsten, A, Hartung, H-P, Heard, RN, Heath, S, Hobart, J, Hoshi, M, Infante-Duarte, C, Ingram, G, Ingram, W, Islam, T, Jagodic, M, Kabesch, M, Kermode, AG, Kilpatrick, TJ, Kim, C, Klopp, N, Koivisto, K, Larsson, M, Lathrop, M, Lechner-Scott, JS, Leone, MA, Leppa, V, Liljedahl, U, Bomfim, IL, Lincoln, RR, Link, J, Liu, J, Lorentzen, AR, Lupoli, S, Macciardi, F, Mack, T, Marriott, M, Martinelli, V, Mason, D, McCauley, JL, Mentch, F, Mero, I-L, Mihalova, T, Montalban, X, Mottershead, J, Myhr, K-M, Naldi, P, Ollier, W, Page, A, Palotie, A, Pelletier, J, Piccio, L, Pickersgill, T, Piehl, F, Pobywajlo, S, Quach, HL, Ramsay, PP, Reunanen, M, Reynolds, R, Rioux, J, Rodegher, M, Roesner, S, Rubio, JP, Rueckert, I-M, Salvetti, M, Salvi, E, Santaniello, A, Schaefer, CA, Schreiber, S, Schulze, C, Scott, RJ, Sellebjerg, F, Selmaj, KW, Sexton, D, Shen, L, Simms-Acuna, B, Skidmore, S, Sleiman, PMA, Smestad, C, Sorensen, PS, Sondergaard, HB, Stankovich, J, Strange, RC, Sulonen, A-M, Sundqvist, E, Syvaenen, A-C, Taddeo, F, Taylor, B, Blackwell, JM, Tienari, P, Bramon, E, Tourbah, A, Brown, MA, Tronczynska, E, Casas, JP, Tubridy, N, Corvin, A, Vickery, J, Jankowski, J, Villoslada, P, Markus, HS, Wang, K, Mathew, CG, Wason, J, Palmer, CNA, Wichmann, H-E, Plomin, R, Willoughby, E, Rautanen, A, Winkelmann, J, Wittig, M, Trembath, RC, Yaouanq, J, Viswanathan, AC, Zhang, H, Wood, NW, Zuvich, R, Deloukas, P, Langford, C, Duncanson, A, Oksenberg, JR, Pericak-Vance, MA, Haines, JL, Olsson, T, Hillert, J, Ivinson, AJ, De Jager, PL, Peltonen, L, Stewart, GJ, Hafler, DA, Hauser, SL, McVean, G, Donnelly, P, 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Piehl, F, Pobywajlo, S, Quach, HL, Ramsay, PP, Reunanen, M, Reynolds, R, Rioux, J, Rodegher, M, Roesner, S, Rubio, JP, Rueckert, I-M, Salvetti, M, Salvi, E, Santaniello, A, Schaefer, CA, Schreiber, S, Schulze, C, Scott, RJ, Sellebjerg, F, Selmaj, KW, Sexton, D, Shen, L, Simms-Acuna, B, Skidmore, S, Sleiman, PMA, Smestad, C, Sorensen, PS, Sondergaard, HB, Stankovich, J, Strange, RC, Sulonen, A-M, Sundqvist, E, Syvaenen, A-C, Taddeo, F, Taylor, B, Blackwell, JM, Tienari, P, Bramon, E, Tourbah, A, Brown, MA, Tronczynska, E, Casas, JP, Tubridy, N, Corvin, A, Vickery, J, Jankowski, J, Villoslada, P, Markus, HS, Wang, K, Mathew, CG, Wason, J, Palmer, CNA, Wichmann, H-E, Plomin, R, Willoughby, E, Rautanen, A, Winkelmann, J, Wittig, M, Trembath, RC, Yaouanq, J, Viswanathan, AC, Zhang, H, Wood, NW, Zuvich, R, Deloukas, P, Langford, C, Duncanson, A, Oksenberg, JR, Pericak-Vance, MA, Haines, JL, Olsson, T, Hillert, J, Ivinson, AJ, De Jager, PL, Peltonen, L, Stewart, GJ, Hafler, DA, Hauser, SL, McVean, G, Donnelly, P, and Compston, A

Abstract

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

Published
2011

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