| 1. |
- Berndt, Sonja, I, et al.
(författare)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Tidskriftsartikel (refereegranskat)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 2. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 3. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 4. |
- Abata, E., et al.
(författare)
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Study of energy response and resolution of the ATLAS barrel calorimeter to hadrons of energies from 20 to 350 GeV
- 2010
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576 .- 0167-5087. ; 621:1-3, s. 134-150
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Tidskriftsartikel (refereegranskat)abstract
- A fully instrumented slice of the ATLAS detector was exposed to test beams from the SPS (Super Proton Synchrotron) at CERN in 2004. In this paper, the results of the measurements of the response of the barrel calorimeter to hadrons with energies in the range 20-350 GeV and beam impact points and angles corresponding to pseudo-rapidity values in the range 0.2-0.65 are reported. The results are compared to the predictions of a simulation program using the Geant 4 toolkit. (C) 2010 Published by Elsevier B.V.
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| 5. |
- Andersson, Alfred, et al.
(författare)
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Evaluating a Mobility Service Application for Business Travel: Lessons Learnt from a Demonstration Project
- 2020
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Ingår i: Sustainability (Switzerland). - : MDPI AG. - 2071-1050. ; 12:3, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- Business travel contributes to significant greenhouse gas emissions, and there is a need for measures that reduce the demand for trips made with energy-intensive means of transport. In this study, a mobility service application (MSA) introduced in 13 Swedish organisations was tested and evaluated to facilitate booking and handling of business trips, in particular public transport. A before and after study consisting of surveys and interviews with employees at the organisations were conducted. The results show that the MSA was mostly used for regional and local public transport trips, and the users stated that the MSA made it easier to travel by public transport, although this particular result should be seen as tentative due to the small sample size. Three factors that influence the success of a new MSA as a means to increase sustainable business trips were identified: management control and proactiveness; perceived improvement of intervention; functions and technical sufficiency. The results also highlight the need to establish organisational conditions that facilitate sustainable business travel, such as coherent travel policy, accessibility to sustainable modes of transport, and a culture that encourages environmentally friendly behaviour. The study suggests improvements that can be made to similar interventions and strategies that can be introduced to promote sustainable business travel.
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| 6. |
- Benatar, Michael, et al.
(författare)
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Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
- 2024
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
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| 7. |
- Bentley, Michael J., et al.
(författare)
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A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum
- 2014
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse la. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community.
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| 8. |
- Berg, Johanna, et al.
(författare)
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OpenChart-SE: A corpus of artificial Swedish electronic health records for imagined emergency care patients written by physicians in a crowd-sourcing project
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Electronic health records (EHRs) are a rich source of information for medical research and public health monitoring. Information systems based on EHR data could also assist in patient care and hospital management. However, much of the data in EHRs is in the form of unstructured text, which is difficult to process for analysis. Natural language processing (NLP), a form of artificial intelligence, has the potential to enable automatic extraction of information from EHRs and several NLP tools adapted to the style of clinical writing have been developed for English and other major languages. In contrast, the development of NLP tools for less widely spoken languages such as Swedish has lagged behind. A major bottleneck in the development of NLP tools is the restricted access to EHRs due to legitimate patient privacy concerns. To overcome this issue we have generated a citizen science platform for collecting artificial Swedish EHRs with the help of Swedish physicians and medical students. These artificial EHRs describe imagined but plausible emergency care patients in a style that closely resembles EHRs used in emergency departments in Sweden. In the pilot phase, we collected a first batch of 50 artificial EHRs, which has passed review by an experienced Swedish emergency care physician. We make this dataset publicly available as OpenChart-SE corpus (version 1) under an open-source license for the NLP research community. The project is now open for general participation and Swedish physicians and medical students are invited to submit EHRs on the project website (https://github.com/Aitslab/openchart-se). Additional batches of quality-controlled EHRs will be released periodically.
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| 9. |
- Berg, Jessica, et al.
(författare)
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Unga på moped : en studie av riskgrupper och riktade polisinsatser för att motverka trimning
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Unrestricted or so-called trimmed mopeds and speeding are experienced as an increasing traffic safety problem. There is a risk of an increased number of seriously injured and casualties among adolescents as a consequence of the increased number of mopeds found in traffic today and the higher speeds they are driven at. One common police action to reduce trimming is to follow the moped riders who are suspected of altering their vehicles. This can lead to "chase situations" which increase the risk to both moped riders and fellow road-users. One purpose of this report is to study the effects of an alternative way of working with the moped problems by the police in four different towns and by interviews, observations and a questionnaire study broaden our knowledge about attitudes to moped riding and trimming among youths. The results showed that the efforts of the police in the experiment towns had not had any effect on the attitudes and the points of view of the youths towards traffic safety. One possible reason for this is that the method used is too new and that it was not extensive enough. Parents have an effect on the attitude of the youths towards trimming. The parents of those who trim seem to have a more tolerant attitude towards trimming. The results from the questionnaire study show that those that had driven but do not a moped but did not have av moped of their own, as well as those who have a trimmed moped of their own were more positive towards taking risks in traffic, would consider driving at faster speeds and had more experience of traffic offenses. In addition, they are of the opinion that parents, friends and fellow roadusers find it acceptable to exceed the speed limits. Furthermore, these two groups were not as involved in organised leisure activities as the other two groups, their parents were not as strict, grades were not considered as important and they indicated to a greater degree that attending school is difficult or boring. Based on this study, it can be concluded that trimming is not an isolated behaviour but related to a certain lifestyle. In order to reduce trimming an increased understanding of those mechanisms which determine the behaviour of the target groups are needed as well as improved methods to detect trimming. Qualitative studies could be used to discuss the problem with parents, youths and those living in special residential areas where the problem is experienced as being widespread. It might also be interesting to analyse incoming calls/complaints to police communication centres and evaluate the effects police work has on the number of trimmed mopeds over a period of time.
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| 10. |
- Berg, Petra, et al.
(författare)
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Towards a Model for Assessing the Effects of Social-Cyber-Physical Threats on the Future Power Grid - Review and Workshop Results
- 2024
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Ingår i: 2024 International Workshop on Artificial Intelligence and Machine Learning for Energy Transformation, AIE 2024. - : Institute of Electrical and Electronics Engineers (IEEE).
-
Konferensbidrag (refereegranskat)abstract
- The energy system, including the electrical power system, is currently undergoing major changes to meet increased demands and climate target plans, and to stand against potential malicious activities and all sorts of disruptions. Specifically, the electrical power system is drastically changing with regards to consumption, production, transmission, control, monitoring, markets, and digitalization. Such a change, however, makes the power system an attractive and vulnerable target to all kinds of disruptive events and social-cyber-physical attacks since the system is crucial for the functioning of the society and economy. In this work, to act against such events and to study the future power system's susceptibility and resilience towards social-cyber-physical attacks, the Resilient Digital Sustainable Energy Transition (REDISET) project has shown the need for a new model that is able to describe the future electrical power system in a way that reflects the future reality. In this paper, existing power system models, the changing landscape of power systems, the drivers for a new model, the suggested model that comprises 7 building blocks instead of today's 3, and finally a direction of future related work are presented.
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| 11. |
- Dimitrakopoulou, Vasiliki I., et al.
(författare)
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Interactions between genome-wide significant genetic variants and circulating concentrations of 25-Hydroxyvitamin D in relation to prostate cancer risk in the National Cancer Institute BPC3
- 2017
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 185:6, s. 452-464
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified over 100 single nucleotide polymorphisms (SNPs) associated with prostate cancer. However, information on the mechanistic basis for some associations is limited. Recent research has been directed towards the potential association of Vitamin D concentrations and prostate cancer, but little is known about whether the aforementioned genetic associations are modified by Vitamin D. We investigated the associations of 46 GWAS-identified SNPs, circulating concentrations of 25-hydroxyVitamin D (25 (OH)D), and prostate cancer (3,811 cases, 511 of whom died from the disease, compared with 2,980 controls- from 5 cohort studies that recruited participants over several periods beginning in the 1980s). We used logistic regression models with data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) to evaluate interactions on the multiplicative and additive scales. After allowing for multiple testing, none of the SNPs examined was significantly associated with 25(OH)D concentration, and the SNP-prostate cancer associations did not differ by these concentrations. A statistically significant interaction was observed for each of 2 SNPs in the 8q24 region (rs620861 and rs16902094), 25(OH)D concentration, and fatal prostate cancer on both multiplicative and additive scales (P ≥ 0.001). We did not find strong evidence that associations between GWASidentified SNPs and prostate cancer are modified by circulating concentrations of 25(OH)D. The intriguing interactions between rs620861 and rs16902094, 25(OH)D concentration, and fatal prostate cancer warrant replication.
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| 12. |
- Forward, Sonja, et al.
(författare)
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En utvärdering av den utökade riskutbildningen för B-körkort : delstudie 4
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den 1 juli 1999 ersattes den traditionella halkutbildningen med en ny, utökad riskutbildning för B-körkort. Målet var att lägga mer tonvikt på riskmedvetenhet, förutseende körsätt och insikt om egna begränsningar. Syftet med föreliggande rapport är att redovisa resultatet från en utvärdering som genomfördes före och efter genomförandet av den nya utbildningen. Studien genomfördes som en enkätstudie och målgruppen var nyblivna körkortstagare mellan 18 och 24 år. Resultaten baseras på 1 403 personer. Resultaten visar att deltagarna i efterstudien angav att de under utbildningen lärt sig mer om alkohol/droger och trötthet än deltagarna i förstudien. De ansåg också att de lärt sig mindre om körning på halt väglag, ABS-bromsar och antisladdsystem. Resultaten från kunskapsfrågorna visar att deltagarna i efterstudien hade en bättre kunskap om promillegräns för rattfylleri, krockvåld och ABS-bromsar. Deras inställning till trötthet och bilkörning förändrades. I viss mån var man också mer medveten om vad man borde göra för att motverka trötthet men man förespråkade fortfarande några felaktiga strategier. I likhet med deltagarnas inställning ändrades även deras intentioner men tyvärr inte alltid i rätt riktning. Sammanfattningsvis visar resultaten att de deltagare som genomgått den utökade riskutbildningen fått ökad kunskap och en trafiksäkrare inställning även om detta inte alltid avspeglade sig i en mera trafiksäker intention.
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| 13. |
- Forward, Sonja, 1956-, et al.
(författare)
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Kombinerad mobilitet för hållbara tjänsteresor
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med studien var att uppnå ett mer hållbart tjänsteresande genom att demonstrera och utvärdera en ny tjänst för kombinerad mobilitet för tjänsteresor. Ett annat syfte var att undersöka hur tjänsteresor inklusive resfria möten (dvs. virtuella möten som sker på distans) genomförs i organisationer och vad som påverkar val av transporter. I studien ingick en processutvärdering, en intervjustudie och en effektutvärdering. Intervjustudien, som bygger på intervjuer och fokusgrupper med 38 personer från 12 organisationer, visade att man rent allmänt var nöjd med rese-appen och kunde se fördelarna med att använda en sådan. De som var mindre nöjda ansåg att tekniken inte fungerade fullt ut. Svaren från enkätstudien visade att även om deltagarna var nöjda använde de den inte regelbundet utan mest då de skulle göra regionala resor. Detta innebar att färre använt appen för lokala bussresor och långväga tågresor vilket kan bero på att de hade egna resekort och avtal med en resebyrå. Detta stöds även av processutvärderingen som visade att lanseringen av appen var svårare än man förväntat sig, vilket många gånger berodde på att organisationerna hade egna lösningar. I effektutvärderingen jämfördes även svaren från de som använt och de som inte använt rese-appen. Resultatet visade att gruppen som använt appen ansåg att det blivit mindre besvärligt att resa med buss jämfört med svaren i förstudien. Någon liknande förändring hade inte skett i kontrollgruppen. På frågor om resfria möten ansåg ungefär hälften att det var lätt eller mycket lätt att ordna ett sådant möte. Anledningen till att man inte utnyttjade denna möjligt var att man kände sig osäker på hur tekniken skulle hanteras. Resultaten visade att det fanns en potential att ersätta ca en femtedel av tjänsteresorna med resfria möten. En viktig slutsats från studien var att utformningen av appen fungerade bra men att utbudet i egna kanaler som man redan använder inte får skilja sig för mycket med appen. Om appen sedan ökar användningen av mera hållbara transporter behöver undersökas ytterligare över en längre tid och med en större grupp.
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| 14. |
- Forward, Sonja, et al.
(författare)
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Utvärdering av en ny obligatorisk riskutbildning för motorcyklister
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Från den 1 november 2009 infördes en obligatorisk riskutbildning för behörighet A och A1 (tung respektive lätt motorcykel). Utbildningen är både teoretisk och praktisk och specifikt riktad till motorcyklister. Syftet med föreliggande studie är att undersöka om det skett någon förändring i synen på risktagning efter införandet av den nya riskutbildningen. Undersökningen genomfördes i form av en webbenkätstudie och två olika grupper jämfördes: de somavslutade mc-utbildningen före riskutbildningens införande den 1 november 2009 och de som avslutadeutbildningen efter detta datum. I studien deltog 1 472 personer (förstudie=541; efterstudie=931).Medelåldern var 30 år och andelen kvinnor 20 procent. Resultaten visar att det skett relativt småförändringar i attityder, normer och intentioner i jämförelsen mellan för- och efterstudie. De skillnadersom konstaterades gick oftast i ”rätt” riktning, det vill säga en ökad förståelse för olika risker. De negativa förändringar som kan ses finns främst inom den yngsta gruppen (16-–20 år) avseende hastighet, alkohol, trötthet och synen på den egna förmågan i jämförelse med andra motorcyklister. Sammanfattningsvis visar studien att det dels finns behov av ytterligare studier av utbildningens effekter, dels utbildningens form och upplägg avseende till exempel pedagogik riktat till specifika målgrupper. Hur de aktuella resultaten kan hjälpa till att utveckla den obligatoriska riskutbildningen för behörighet A och A1 diskuteras.
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| 15. |
- Gu, Fangyi, et al.
(författare)
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Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer
- 2010
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 19:11, s. 2877-2887
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins.Methods: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.Results: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 × 10−4); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R2 = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers.Conclusion: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women.Impact: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes.
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| 16. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 17. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 18. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 19. |
- Jonsson, Annie, et al.
(författare)
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Landskapets förmåga att hålla biologisk mångfald : – en indikator för biologisk mångfald och ett planeringsverktyg för prioritering av markanvändning
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten beskriver ett nytt verktyg framtaget för att underlätta planering av grön infrastruktur på landskapsnivå och ger via fallstudier exempel på hur verktyget kan användas. Projektet har utförts i ett samarbete med expertis inom teoretisk ekologi, ekologi, biodiversitetsinformatik och tillämpad matematik.Forskningsprojektet har utvecklat en modell för att uppskatta ett landskaps för-måga att hålla biologisk mångfald i dess olika biotoper (Biotope Biodiversity Capacity Indicator, BBCI). Ett teoretiskt ramverk baserat på ekologisk kunskap har tagits fram som grund för modellen.Syftet med BBCI är att modellen ska kunna användas som ett planeringsverktyg för att:stärka biologisk mångfald i ett landskap,förbättra förutsättningarna för arter att använda hela landskapet ochskapa bättre förutsättningar för hänsyn till biologisk mångfald i samband med samhällsutveckling.För att testa och beskriva verktygets användbarhet har fyra fallstudier genomförts med olika fokus:Analys av fragmenteringen i ett barrskogslandskap som sköts med särskild naturhänsyn i Västernorrlands län.Analys av barrskogsvärdekärnors kapacitet för biologisk mångfald inom Västra Götalands län som synliggör vikten av kommunöverskridande samverkan.Analys av potentiella målkonflikter mellan två biotoper, ädellövskog och öppen mark med skyddsvärda träd i Valle.Analys av kapacitet för biologisk mångfald hos äldre ädellövträd i ett landskap mixat med urbana miljöer och landsbygd, Mjölby kommun.Parallellt med utvcklingen av BBCI har en tät dialog och samverkan skett med olika intressenter och slutanvändare. Den breda dialogen har medfört ett effektivt kun-skapsutbyte mellan olika parter.Rapporten avslutas med att beskriva utmaningar och verktygets utvecklings-potential både avseende pedagogik och teknik men även hur modellen kan byggas på och utvecklas med ytterligare funktioner för en breddad tillämpning.
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| 20. |
- Kivinen, Sonja, et al.
(författare)
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Effects of modern forest management on winter grazing resources for reindeer in Sweden
- 2010
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 39:4, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- Boreal forests in Sweden are exploited in a number of ways, including forestry and reindeer husbandry. In the winter, reindeer feed mainly on lichens, and lichen-rich forests are a key resource in the herding system. Commercial forestry has mainly negative effects on reindeer husbandry, and conflicts between these two industries have escalated over the last century. This article reviews the effects of modern forest management practices on the winter resources available for reindeer husbandry. Forestry affects reindeer husbandry at both the stand level and the landscape level and over various time scales. Clear-cutting, site preparation, fertilization, short rotation times, and forest fragmentation have largely resulted in a reduced amount of ground growing and arboreal lichens and restricted access to resource. This article also discusses alternative forestry practices and approaches that could reduce the impacts of forestry on reindeer husbandry, both in the short and long term.
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| 21. |
- Kivinen, Sonja, et al.
(författare)
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Forest Fragmentation and Landscape Transformation in a Reindeer Husbandry Area in Sweden
- 2012
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Ingår i: Environmental Management. - New York : Springer-Verlag New York. - 0364-152X .- 1432-1009. ; 49:2, s. 295-304
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Tidskriftsartikel (refereegranskat)abstract
- Reindeer husbandry and forestry are two main land users in boreal forests in northern Sweden. Modern forestry has numerous negative effects on the ground-growing and arboreal lichens that are crucial winter resources for reindeer husbandry. Using digitized historical maps, we examined changes in the forest landscape structure during the past 100 years, and estimated corresponding changes in suitability of forest landscape mosaics for the reindeer winter grazing. Cover of old coniferous forests, a key habitat type of reindeer herding system, showed a strong decrease during the study period, whereas clear-cutting and young forests increased rapidly in the latter half of the 20th century. The dominance of young forests and fragmentation of old-growth forests (decreased patch sizes and increased isolation) reflect decreased amount of arboreal lichens as well as a lowered ability of the landscape to sustain long-term persistence of lichens. The results further showed that variation in ground lichen cover among sites was mainly related to soil moisture conditions, recent disturbances, such as soil scarification and prescribed burning, and possibly also to forest history. In general, the results suggest that the composition and configuration of the forest landscape mosaic has become less suitable for sustainable reindeer husbandry.
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| 22. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 23. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 24. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 25. |
- Parmar, Priyanka, et al.
(författare)
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Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults
- 2018
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 38, s. 206-216
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0.012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 x 10(-7) < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 10(-8) < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. Fund: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.
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| 26. |
- Robinson, Matthew R., et al.
(författare)
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Population genetic differentiation of height and body mass index across Europe
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47:11, s. 1357-1362
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Tidskriftsartikel (refereegranskat)abstract
- Across-nation differences in the mean values for complex traits are common(1-8), but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 x 10(-8); BMI, P < 5.95 x 10(-4)), and we find an among-population genetic correlation for tall and slender individuals (r = -0.80, 95% CI = -0.95, -0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).
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| 27. |
- Schmit, Stephanie L, et al.
(författare)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 28. |
- Shui, Irene M., et al.
(författare)
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Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
- 2014
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 65:6, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Background: Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM). Objective: To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM. Design, setting, and participants: We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred. Outcome measurements and statistical analysis: The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls. Results and limitations: Among the cases, we found that 8 of the 47 SNPs were significantly associated (p < 0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p < 0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only. Conclusions: Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. Patient summary: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 29. |
- van Es, Michael A, et al.
(författare)
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Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis.
- 2008
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:1, s. 29-31
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Tidskriftsartikel (refereegranskat)abstract
- We identified a SNP in the DPP6 gene that is consistently strongly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in different populations of European ancestry, with an overall P value of 5.04 x 10(-8) in 1,767 cases and 1,916 healthy controls and with an odds ratio of 1.30 (95% confidence interval (CI) of 1.18-1.43). Our finding is the first report of a genome-wide significant association with sporadic ALS and may be a target for future functional studies.
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| 30. |
- van Es, Michael A, et al.
(författare)
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ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis : a genome-wide association study.
- 2007
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 6:10, s. 869-77
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease characterised by progressive degeneration of motor neurons in the brain and spinal cord. ALS is thought to be multifactorial, with both environmental and genetic causes. Our aim was to identify genetic variants that predispose for sporadic ALS. METHODS: We did a three-stage genome-wide association study in 461 patients with ALS and 450 controls from The Netherlands, using Illumina 300K single-nucleotide polymorphism (SNP) chips. The SNPs that were most strongly associated with ALS were analysed in a further 876 patients and 906 controls in independent sample series from The Netherlands, Belgium, and Sweden. We also investigated the possible pathological functions of associated genes using expression data from whole blood of patients with sporadic ALS and of control individuals who were included in the genome-wide association study. FINDINGS: A genetic variant in the inositol 1,4,5-triphosphate receptor 2 gene (ITPR2) was associated with ALS (p=0.012 after Bonferroni correction). Combined analysis of all samples (1337 patients and 1356 controls) confirmed this association (p=3.28x10(-6), odds ratio 1.58, 95% CI 1.30-1.91). ITPR2 expression was greater in the peripheral blood of 126 ALS patients than in that of 126 healthy controls (p=0.00016). INTERPRETATION: Genetic variation in ITPR2 is a susceptibility factor for ALS. ITPR2 is a strong candidate susceptibility gene for ALS because it is involved in glutamate-mediated neurotransmission, is one of the main regulators of intracellular calcium concentrations, and has an important role in apoptosis.
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