| 1. |
- Finnsgård, Christian, 1974, et al.
(författare)
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Impact of materials exposure on assembly workstation performance
- 2011
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Ingår i: International Journal of Production Research. - : Informa UK Limited. - 0020-7543 .- 1366-588X. ; 49:24, s. 7253-7274
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines how the choice of materials exposure impacts workstation performance, in terms of non-value-adding work, space requirements and ergonomics. In a typical Swedish automotive setting, components are exposed in wooden pallets with frames beside the assembly line and supplied by forklift truck. In a case study, three workstations on an assembly line were studied and redesigned following the principles of lean production, using smaller plastic containers for the materials exposure. After the redesign, the space required for materials was reduced by 67%, non-value-adding work decreased by 20%, and walking distance was reduced by 52%. Furthermore, the ergonomics for the assembly operator improved greatly, with a 92% reduction of potentially harmful picking activities, thereby almost eliminating potentially harmful body movements. The theoretical contribution of this paper is firstly the development of an analysis model describing the impact of material exposure on workstation performance and secondly development of the existing categorization of work operations to include different materials handling activities. The most important managerial implication is an increased understanding of the relationship between space, ergonomics, non-value-adding work and materials exposure. These findings have direct implications on workstation design in industry.
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| 2. |
- Forsman, Mikael, et al.
(författare)
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Mechanical exposures in serial flow assembly - a proactive intervention research approach
- 2013
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The EU End of Life Vehicle (ELV) Directive 2000/53/EC has prompted rationalization initiatives to facilitate recycling of material and components from ELVs. In the present study, technical recordings were used to assess operators' mechanical exposures in a new serial flow system for full material recovery in car disassembly as compared with those of a previous study of traditional craft-type-parallel disassembly. Estimated task-specific mechanical exposures served as a base to simulate how further rationalisation may affect ergonomics in car disassembly. The time proportion of ‘direct work’ (deemed value-adding tasks) was about 30% in both systems, i.e. substantially lower than in modern forward factories. Movement velocities were higher in the new serial system, implying a higher risk for musculoskeletal disorders, while mixed results were found in the comparison of postures.Simulations revealed increased mechanical exposures, illustrated by increased time in high risk conditions, and decreased duration in low-exposure conditions, when indirect tasks and disturbances (deemed non-value-adding) were removed.This may illustrate the underlying mechanism of how rationalisations to eliminate "waste" can reduce valuable recovery time and increase employee injury risk over time.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Gallagher, Michael D., et al.
(författare)
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TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 127:3, s. 407-418
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Tidskriftsartikel (refereegranskat)abstract
- Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease.
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| 7. |
- Hamp, Quirin, et al.
(författare)
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Study of efficiency of USAR operations with assistive technologies
- 2013
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Ingår i: Advanced Robotics. - : Informa UK Limited. - 0169-1864 .- 1568-5535. ; 27:5, s. 337-350
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents presents a study on eciency of Urban Search and Rescue (USAR) missions that has been carried out within the framework of the German research project I-LOV. After three years of development, first field tests have been carried out in 2011 by professionals such as the Rapid Deployment Unit for Salvage Operations Abroad (SEEBA). We present results from evaluating search teams in simulated USAR scenarios equipped with newly developed technical search means and digital data input terminals developed in the I-LOV project. In particular, USAR missions assisted by the “bioradar”, a ground-penetrating radar system for the detection of humanoid movements, a semi-active video probe of more than 10 m length for rubble pile exploration, a snake-like rescue robot, and the decision support system FRIEDAA were evaluated and compared with conventional USAR missions. Results of this evaluation indicate that the developed technologies represent an advantages for USAR missions, which are discussed in this paper.
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| 8. |
- Hernandez Bennetts, Victor, et al.
(författare)
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Mobile robots for localizing gas emission sources on landfill sites : is bio-inspiration the way to go?
- 2012
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Ingår i: Frontiers in Neuroengineering. - : Frontiers Media S.A.. - 1662-6443. ; 4:20, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Roboticists often take inspiration from animals for designing sensors, actuators, or algorithms that control the behavior of robots. Bio-inspiration is motivated with the uncanny ability of animals to solve complex tasks like recognizing and manipulating objects, walking on uneven terrains, or navigating to the source of an odor plume. In particular the task of tracking an odor plume up to its source has nearly exclusively been addressed using biologically inspired algorithms and robots have been developed, for example, to mimic the behavior of moths, dung beetles, or lobsters. In this paper we argue that biomimetic approaches to gas source localization are of limited use, primarily because animals differ fundamentally in their sensing and actuation capabilities from state-of-the-art gas-sensitive mobile robots. To support our claim, we compare actuation and chemical sensing available to mobile robots to the corresponding capabilities of moths. We further characterize airflow and chemosensor measurements obtained with three different robot platforms (two wheeled robots and one flying micro-drone) in four prototypical environments and show that the assumption of a constant and unidirectional airflow, which is the basis of many gas source localization approaches, is usually far from being valid. This analysis should help to identify how underlying principles, which govern the gas source tracking behavior of animals, can be usefully translated into gas source localization approaches that fully take into account the capabilities of mobile robots. We also describe the requirements for a reference application, monitoring of gas emissions at landfill sites with mobile robots, and discuss an engineered gas source localization approach based on statistics as an alternative to biologically inspired algorithms.
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| 9. |
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| 10. |
- Neumann, Patrick, et al.
(författare)
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Adaptive gas source localization strategies and gas distribution mapping using a gas-sensitive micro-drone
- 2012
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Ingår i: Proceedings of the 16th ITG / GMA Conference. - Wunstorf : AMA Service. - 9783981348408 ; , s. 800-809
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Konferensbidrag (refereegranskat)abstract
- In this paper we exemplify how to address environmental monitoring tasks with a gas-sensitive micro-drone and present two different approaches to locate gas emission sources. First, we sent the micro-drone in real-world experiments along predefined sweeping trajectories to model the gas distribution. The identification of the gas source location is made afterwards based on the created model. Second, we adapted two bio-inspired plume tracking algorithms that have been implemented so far on ground-based mobile robots. We developed a third bio-inspired algorithm, which is called “pseudo gradient-based algorithm”, and compared its perfomance in real-world experiments with the other two algorithms.Keywords: Anemotaxis, chemotaxis, micro UAV, bio-inspired, chemical sensing, gas distribution modeling, gas source localization, gas sensors, mobile sensing system, odor localization, olfaction, plume tracking, quadrocopter.
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| 11. |
- Neumann, Patrick, et al.
(författare)
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An artificial potential field based sampling strategy for a gas-sensitive micro-drone
- 2011
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Konferensbidrag (refereegranskat)abstract
- This paper presents a sampling strategy for mobile gas sensors. Sampling points are selected using a modified artificial potential field (APF) approach, which balances multiple criteria to direct sensor measurements towards locations of high mean concentration, high concentration variance and areas for which the uncertainty about the gas distribution model is still large. By selecting in each step the most often suggested close-by measurement location, the proposed approach introduces a locality constraint that allows planning suitable paths for mobile gas sensors. Initial results in simulation and in real-world experiments witha gas-sensitive micro-drone demonstrate the suitability of the proposed sampling strategy for gas distribution mapping and its use for gas source localization.
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| 12. |
- Neumann, Patrick, et al.
(författare)
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Consumer demand as a driver of improved working conditions : the 'Ergo-Brand' proposition
- 2014
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 57:8, s. 1113-1126
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Tidskriftsartikel (refereegranskat)abstract
- This paper develops and explores the “Ergo-Brand” proposition; which posits that consumersmay prefer to buy goods that are made under good working conditions (GWC). This preferencewould enhance a differentiation strategy for companies, thereby fostering the application ofergonomics in production. This proposition is developed in the context of a narrative review ofthe literature on ‘ethical consumerism’. This is supplemented with a small pilot survey study,conducted in both Canada and Sweden (n=141) to explore this proposition. Results indicate thatconsumers would prefer goods made under GWC, but not unconditionally as quality and priceconcerns were ranked higher. Access to information on the working conditions in productionwas seen as a barrier. Nevertheless, the Ergo-Brand concept may be a viable avenue topromoting attention to ergonomics in companies – particularly if consumer habits are subject tointervention by advertising. Further research on this strategy is warranted.
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| 13. |
- Neumann, Patrick, et al.
(författare)
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Ergonomic and technical aspects in the redesign of material supply systems: Big boxes vs. narrow bins
- 2010
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Ingår i: International Journal of Industrial Ergonomics. - : Elsevier BV. - 1872-8219 .- 0169-8141. ; 40:5, s. 541-548
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a design stage comparison of an existing ‘big box’ material supply strategy common in Swedish manufacturing to a proposed ‘narrow bin’ approach common in Japanese production systems. Performance times, walking distances, layout space requirements were evaluated for 6 workstations using ‘big boxes’ of parts along the line. Biomechanical loading on spine and shoulder was estimated for one of the workstations. Comparisons were made to simulated layouts with the ‘narrow bin’ approach. The use of narrow bin supply yielded significant reductions in rack lengths (−81%), Material Areas (−61%), Walking Distances (−61%), Indirect Work (−24%), and Cycle times (−8%). Peak and cumulative spinal load estimates showed reductions from 29% to 65% with similar load reductions in shoulders and hands. The ‘narrow bin’ strategy also has implications for the material re-supply system, enables the use of flexible racking and can reduce lift-truck use. Work intensification may increase risks if time-gains are used only to increase direct assembly work repetitions. It is concluded that the narrow bin supply strategy has potential to both improve productivity and reduce risk characteristics of the system. Further field testing is required.Relevance to industry: Supplying materials in smaller narrower bins poses a potential ‘win-win’ design tactic with decreased operator risks and improved performance in final assembly when compared to ‘big box’ supply strategies. The final choice of strategy requires a context-specific assessment.
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| 14. |
- Neumann, Patrick, et al.
(författare)
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Gas source localization with a micro-drone using bio-inspired and particle filter-based algorithms
- 2013
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Ingår i: Advanced Robotics. - : Informa UK Limited. - 0169-1864 .- 1568-5535. ; 27:9, s. 725-738
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Tidskriftsartikel (refereegranskat)abstract
- Gas source localization (GSL) with mobile robots is a challenging task due to the unpredictable nature of gas dispersion,the limitations of the currents sensing technologies, and the mobility constraints of ground-based robots. This work proposesan integral solution for the GSL task, including source declaration. We present a novel pseudo-gradient-basedplume tracking algorithm and a particle filter-based source declaration approach, and apply it on a gas-sensitivemicro-drone. We compare the performance of the proposed system in simulations and real-world experiments againsttwo commonly used tracking algorithms adapted for aerial exploration missions.
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| 15. |
- Neumann, Patrick, et al.
(författare)
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Monitoring of CCS areas using micro unmanned aerial vehicles (MUAVs)
- 2013
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Ingår i: Energy Procedia. - : Elsevier BV. - 1876-6102. ; 37, s. 4182-4190
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Tidskriftsartikel (refereegranskat)abstract
- Carbon capture & storage (CCS) is one of the most promis ing technologies for greenhouse gas (GHG) management.However, an unsolved issue of CCS is the development of appropriate long-term monitoring systems for leakdetection of the stored CO2. To complement already existing monitoring infrastructure for CO2 storage areas, and toincrease the granularity of gas concentration measurements, a quickly deployab le, mobile measurement device isneeded. In this paper, we present an autonomous gas-sensitive micro-drone, which can be used to monitor GHGemissions, more specifically, CO2. Two different measurement strategies are proposed to address this task. First, theuse of predefined sensing trajectories is evaluated for the task of gas distribution mapping using the micro-drone.Alternatively, we present an adaptive strategy, which suggests sampling points based on an artific ial potential field(APF). The results of real-world experiments demonstrate the feas ibility of using gas-sensitive micro-drones for GHG monitoring missions. Thus, we suggest a multi-layered surveillance system for CO2 storage areas.
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| 16. |
- Neumann, Patrick, et al.
(författare)
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On Effect Assessment in Work Environment Interventions : A Literature Overview and Methodological Reflection
- 2010
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Ingår i: Industrial Engineering Publications and Research. - : Ryerson University.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Despite many positive case studies our overview of the work environment intervention (WEI) research literature finds mixed results. There is support for the profitability of WEI investments such as training and personnel policies at the organisational level but less clear results for disorder reductions. The financial benefits of WEIs were greater for performance gains than for reduced sickness costs. Multifactor interventions are widely seen as key to successful intervention but are difficult to evaluate and unused in experimental studies. Review inclusion criteria excluding studies with good interventions but non-experimental evaluations, pose a quality criteria selection bias. Difficulties in proving WEI effectiveness may depend on views of what constitutes good scientific quality. WEI effects are clear in some cases but are difficult to show in others. Evaluation poses methodological challenges that contribute to the lack of clear evidence for WEI effectiveness. There is a need for more practical multifactor WEIs and non-experimental evaluation strategies suited to today’s complex systems.RELEVANCE: Ergonomists and managers should understand that the problems in 'proving' the effectiveness of ergonomics are related to perceptions of what constitutes proof. Progress in the practise of ergonomics should recognise the difficulty of organisational change, the weaknesses of experimental traditions, and the need for multifactor interventions that reach deep into the work process to maximise impact. Isolating effects is difficult but this does not mean no effects exist.
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| 17. |
- Neumann, Patrick P., et al.
(författare)
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A Probabilistic Gas Patch Path Prediction Approach for Airborne Gas Source Localization in Non-Uniform Wind Fields
- 2014
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Ingår i: Sensor Letters. - Valencia, USA : American Scientific Publishers. - 1546-198X .- 1546-1971. ; 12:6-7, s. 1113-1118
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we show that a micro unmanned aerial vehicle (UAV) equipped with commercially available gas sensors can addressenvironmental monitoring and gas source localization (GSL) tasks. To account for the challenges of gas sensing under real-world conditions,we present a probabilistic approach to GSL that is based on a particle filter (PF). Simulation and real-world experiments demonstrate thesuitability of this algorithm for micro UAV platforms.
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| 18. |
- Neumann, Patrick P., et al.
(författare)
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Autonomous gas-sensitive microdrone wind vector estimation and gas distribution mapping
- 2012
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Ingår i: IEEE robotics & automation magazine. - : Institute of Electrical and Electronics Engineers (IEEE). - 1070-9932 .- 1558-223X. ; 19:1, s. 50-61
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Tidskriftsartikel (refereegranskat)abstract
- This article presents the development and validation of an autonomous, gas sensitive microdrone that is capable of estimating the wind vector in real time using only the onboard control unit of the microdrone and performing gas distribution mapping (DM). Two different sampling approaches are suggested to address this problem. On the one hand, a predefined trajectory is used to explore the target area with the microdrone in a real-world gas DM experiment. As an alternative sampling approach, we introduce an adaptive strategy that suggests next sampling points based on an artificial potential field (APF). Initial results in real-world experiments demonstrate the capability of the proposed adaptive sampling strategy for gas DM and its use for gas source localization.
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| 19. |
- Palmerud, Gunnar, 1948, et al.
(författare)
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Mechanical exposure implications of rationalization : A comparison of two flow strategies in a Swedish manufacturing plant
- 2012
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Ingår i: Applied Ergonomics. - : Elsevier BV. - 0003-6870 .- 1872-9126. ; 43:6, s. 1110-1121
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this case study was to (1) investigate differences in mechanical exposure (i.e. mechanical forces arising in the body of the operator) between two production strategies: long-cycle parallelised flow assembly (OLD) and conventional serial flow assembly (NEW), and (2) estimate potential changes in job exposure as a consequence of waste reduction when rationalising a line system.Data on postures, movements and whole body exposure were collected during an ordinary working shift, by means of video recordings synchronised to direct technical measurements of six professional operators.The results revealed the machine paced NEW system to have slower movements with less time spent in movements of high velocity compared to the self-paced OLD system. No significant differences were found between time-median posture levels. ‘Disturbances’ in the NEW system offered lower mechanical risk exposures compared to direct assembly work. Modelling the removal of wasteful ‘disturbances’ revealed both an increase in risk-implying fast movements and decrease in recovery-implying periods at low velocity – effectively isolating a work intensification. This study helps expose the complex relationship between rationalizations and mechanical exposure for system operators
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| 20. |
- Rose, Linda M, 1963-, et al.
(författare)
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Designing Jobs in Manufacturing : Rest Allowances
- 2012
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The organization of work along a conventional production line layout has called for the consideration of both human (e.g., rest breaks, work pace) and technical factors, striving for the optimization of ergonomics and production. Linda Rose and Patrick Neumann discuss these issues in relation to muscle fatigue.
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| 21. |
- Rose, Linda M., et al.
(författare)
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Fatigue and recovery during and after static loading
- 2014
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 57:11, s. 1696-1710
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Tidskriftsartikel (refereegranskat)abstract
- Subjectively assessed endurance time (ET), resumption time (RT) and perceived discomfort, pain or fatigue (PD), and objectively measured maximum force-exerting capacity were investigated for varying loads and durations of a pushing task with two repeated trials. Beyond the main results quantifying how the load scenario affected ET, RT and PD, three additional results are of note: (1) although the maximum pushing force did not change between trials, shorter ET, longer RT and higher PD indicated accumulation of fatigue in Trial 2; (2) the PD ratings showed a trend with a linear increase during loading and a curvilinear decrease during recovery; and (3) the RT and the load level for different relative loading times were found to have an unexpected U-shaped relationship, indicating lowest fatigue at the intermediate load level. These results can be used to model a more sustainable and productive work-recovery ratio.
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| 22. |
- Rose, Linda M., 1963-, et al.
(författare)
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Work Environment and the Bottom Line : Survey of Tools Relating Work Environment to Business Results
- 2013
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Ingår i: Human Factors and Ergonomics in Manufacturing. - : Wiley-Blackwell. - 1090-8471 .- 1520-6564. ; 23:5, s. 368-381
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Tidskriftsartikel (refereegranskat)abstract
- Insufficient knowledge of how the working environment (WE) impacts company performance leads to a poor basis for managerial decision making. The objective of this study was to survey and evaluate available tools relating WE to business results. Nine tools were identified and qualitatively evaluated using 11 criteria. The tools were clustered into three categories, ranging from analysis of WE risks as well as calculation of their economic impact to solely investment analysis. Shortcomings in the tools include insufficient attention to quality and productivity issues and insufficient guidance for users. Although further methodological development is indicated, researchers should also attend to the factors affecting tool uptake and application as well as the potential to integrate such analysis into companies' regular accounting systems.
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| 23. |
- Rose, Linda M., 1963-, et al.
(författare)
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Workshop : Human Factors And The Bottom Line – Quantifying The Benefits Of Healthy Workplaces
- 2014
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Ingår i: 11th International Symposium on Human Factors in Organisational Design and Management (ODAM 2014)and 46th Annual Nordic Ergonomics Society, Technical University of Denmark.
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Konferensbidrag (refereegranskat)abstract
- The aim of the workshopThe workshop gives opportunities to learn about how to banish the phantom of unexpected costs and poor operating performance that comes from ergonomics / Human Factors problems in the workplace. The objectives are to foster a broad discussion on the economics of ergonomics including aspects such as 1) How Human Factors can affect company’s bottom line , 2) Why companies underestimate Ergonomics/Human Factors costs and benefits, 3) What economic assessment tools and approaches can be used to help companies realise the financial benefits of good working environments. The format of the workshopParticipants are invited to join this interactive workshop on quantifying the financial costs and benefits of workplace improvements. The workshop will take an interactive approach. First the hosts will share their experiences, and will be examining a range of economic assessment techniques and discuss case studies in from both Swedish and Canadian industry, of how attending the human factors and ergonomics can improve a company’s productivity and quality performance. Thereafter an open plenary discussion will follow.Work environment effects are often difficult to assess, especially since many of them are hidden. Moreover, the economic impact of these hidden effects is often many times larger than that from visible effects, such as costs from absenteeism. Hidden effects often play a larger role on business parameters than visible ones do. Without adequate measurement or assessment tools, hidden effects remain obscured. As a result, they may be overlooked, which can have significant business consequences, particularly when making investment decisions related to work environment issues. Ergonomics/Human Factors gains from quality and productivity are usually much greater than for reduced compensation costs. Companies that underestimate the financial impact of human aspects of their systems can find their anticipated profits vanish – so called ‘phantom profits’.
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| 24. |
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| 25. |
- Takala, Esa-Pekka, et al.
(författare)
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Systematic evaluation of observational methods assessing biomechanical exposures at work
- 2010
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Finnish Institute of Occupational Health; National Research Centre for the  . - 0355-3140 .- 1795-990X. ; 36:1, s. 3-24
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This systematic review aimed to identify published observational methods assessing biomechanical exposures in occupational settings and evaluate them with reference to the needs of different users.Methods: We searched scientific databases and the internet for material from 1965 to September 2008. Methods were included if they were primarily based on the systematic observation of work, the observation target was the human body, and the method was clearly described in the literature. A systematic evaluation procedure was developed to assess concurrent and predictive validity, repeatability, and aspects related to utility. At least two evaluators independently carried out this evaluation.Results: We identified 30 eligible observational methods. Of these, 19 had been compared with some other method(s), varying from expert evaluation to data obtained from video recordings or through the use of technical instruments. Generally, the observations showed moderate-to-good agreement with the corresponding assessments made from video recordings; agreement was the best for large-scale body postures and work actions. Postures of wrist and hand as well as trunk rotation seemed to be more difficult to observe correctly. Intra- and inter-observer repeatability were reported for 7 and 17 methods, respectively, and were judged mostly to be moderate or good.Conclusions: With training, observers can reach consistent results on clearly visible body postures and work activities. Many observational tools exist, but none evaluated in this study appeared to be generally superior. When selecting a method, users should define their needs and assess how results will influence decision-making
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| 26. |
- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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| 27. |
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