| 1. |
- Willems, S. M., et al.
(författare)
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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality. © The Author(s) 2017.
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| 2. |
- Farina, D., et al.
(författare)
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Toward higher-performance bionic limbs for wider clinical use
- 2021
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Ingår i: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 7:4, s. 473-85
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Tidskriftsartikel (refereegranskat)abstract
- Most prosthetic limbs can autonomously move with dexterity, yet they are not perceived by the user as belonging to their own body. Robotic limbs can convey information about the environment with higher precision than biological limbs, but their actual performance is substantially limited by current technologies for the interfacing of the robotic devices with the body and for transferring motor and sensory information bidirectionally between the prosthesis and the user. In this Perspective, we argue that direct skeletal attachment of bionic devices via osseointegration, the amplification of neural signals by targeted muscle innervation, improved prosthesis control via implanted muscle sensors and advanced algorithms, and the provision of sensory feedback by means of electrodes implanted in peripheral nerves, should all be leveraged towards the creation of a new generation of high-performance bionic limbs. These technologies have been clinically tested in humans, and alongside mechanical redesigns and adequate rehabilitation training should facilitate the wider clinical use of bionic limbs. This Perspective argues that technologies for the neural interfacing of robotic devices with the body that have been clinically tested in humans should be leveraged toward the creation of a new generation of high-performance bionic limbs.
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| 3. |
- Kerkhof, H. J. M., et al.
(författare)
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Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium
- 2011
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 254-264
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. Results: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P=0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3 x 10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. Conclusion: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 4. |
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| 5. |
- Lohmander, Stefan, et al.
(författare)
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Standardized incidence rates of total hip replacement for primary hip osteoarthritis in the 5 Nordic countries: similarities and differences
- 2006
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Ingår i: Acta Orthop. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 77:5, s. 733-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The national hip registers of the Nordic countries provide an opportunity to compare age- and sex-standardized annual incidence of primary total hip replacement (THR) and types of implants used for primary hip osteoarthritis (OA) in Denmark, Finland, Iceland, Norway and Sweden. METHODS: The data on THR were from the national total hip replacement registries, and population data were from the national statistics agencies. Annual incidence density per 100,000 was calculated for each 5-year age group and it was age-standardized using the WHO European standard population. RESULTS: Crude country-specific annual incidence (all ages) for 1996-2000 varied between 73 and 90. WHO age-standardized annual incidence (all ages) varied between 61 (Finland) and 84 (Iceland). For the ages 50-89, comprising 94-98% of all THRs for OA, annual incidence varied between 217 (Finland) and 309 (Iceland). For Norway, the sex incidence ratio (women/men) was 2, and for the other countries it was between 1.1 and 1.3. The use of uncemented and hybrid replacements was considerably higher in Finland and Denmark than in the other countries. INTERPRETATION: We found overall similarity in THR incidence between the 5 Nordic countries, but substantial differences between women and men, and in the use of different types of implant. Population-based, age-standardized and disease-specific information on THR incidence is required in order to properly explore the causes of differences in provision and practice of THR in different countries, regions and groups, and it will aid in projecting future needs.
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| 6. |
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| 7. |
- Styrkarsdottir, Unnur, et al.
(författare)
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Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:5, s. 498-502
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P = 1.1 × 10(-11) (rs3204689).
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| 8. |
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| 9. |
- Cole, Christopher T., et al.
(författare)
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Pathway position constrains the evolution of an ecologically important pathway in aspens (Populus tremula L.)
- 2018
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Ingår i: Molecular Ecology. - : Wiley-Blackwell. - 0962-1083 .- 1365-294X. ; 27:16, s. 3317-3330
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Tidskriftsartikel (refereegranskat)abstract
- Many ecological interactions of aspens and their relatives (Populus spp.) are affected by products of the phenylpropanoid pathway synthesizing condensed tannins (CTs), whose production involves trade-offs with other ecologically important compounds and with growth. Genes of this pathway are candidates for investigating the role of selection on ecologically important, polygenic traits. We analysed sequences from 25 genes representing 10 steps of the CT synthesis pathway, which produces CTs used in defence and lignins used for growth, in 12 individuals of European aspen (Populus tremula). We compared these to homologs from P.trichocarpa, to a control set of 77 P. tremula genes, to genome-wide resequencing data and to RNA-seq expression levels, in order to identify signatures of selection distinct from those of demography. In Populus, pathway position exerts a strong influence on the evolution of these genes. Nonsynonymous diversity, divergence and allele frequency shifts (Tajima's D) were much lower than for synonymous measures. Expression levels were higher, and the direction of selection more negative, for upstream genes than for those downstream. Selective constraints act with increasing intensity on upstream genes, despite the presence of multiple paralogs in most gene families. Pleiotropy, expression level, flux control and codon bias appear to interact in determining levels and patterns of variation in genes of this pathway, whose products mediate a wide array of ecological interactions for this widely distributed species.
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| 10. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 11. |
- Evangelou, Evangelos, et al.
(författare)
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A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:12, s. 2130-2136
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9x10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p= 5.6x10(-8)) and follow-up studies (p=7.3x10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9x10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2x10(-6), OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
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| 12. |
- Evangelou, Evangelos, et al.
(författare)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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| 13. |
- Franklin, Jonas, et al.
(författare)
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Sex differences in the association between body mass index and total hip or knee joint replacement resulting from osteoarthritis
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:4, s. 536-540
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the association between body mass index (BMI) and osteoarthritis (OA) leading to total hip (THR) or knee (TKR) joint replacement. Methods: Case-control study design. All patients still living in Iceland who had had a THR or TKR resulting from OA before the end of 2002 were invited to participate. First-degree relatives of participating patients served as controls. A total of 1473 patients ( 872 women) and 1103 controls ( 599 women), all born between 1910 and 1939 and who had answered a questionnaire including questions about height and weight, were analysed. A randomly selected sample, representative of the Icelandic population, was used as a secondary control group. Results: The OR, adjusted for age, occupation and presence of hand OA, for having a THR was 1.1 (95% CI 0.9 to 1.5) for overweight men and 1.7 ( 95% CI 1.0 to 2.9) for obese men. The OR for having a TKR was 1.7 ( 95% CI 1.1 to 2.6) for overweight men and 5.3 ( 95% CI 2.8 to 10.1) for obese men. The OR for having a THR was 1.0 ( 95% CI 0.8 to 1.3) for overweight women and 1.0 ( 95% CI 0.6 to 1.5) for obese women. The OR for having a TKR was 1.6 ( 95% CI 1.1 to 2.2) for overweight women and 4.0 ( 95% CI 2.6 to 6.1) for obese women. Conclusion: This study supports a positive association between high BMI and TKR in both sexes, but for THR the association with BMI seems to be weaker, and possibly negligible for women.
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| 14. |
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| 15. |
- Hajihoseini, H., et al.
(författare)
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Effect of substrate bias on properties of HiPIMS deposited vanadium nitride films
- 2018
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Ingår i: Thin Solid Films. - : Elsevier B.V.. - 0040-6090 .- 1879-2731. ; 663, s. 126-130
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Tidskriftsartikel (refereegranskat)abstract
- We report on the effect of varying the substrate bias on the morphology, composition, structural, and electrical properties of vanadium nitride films deposited by high power impulse magnetron sputtering (HiPIMS). The optimum substrate bias is found to be −50 V, which gives the highest film density, the lowest electrical resistivity, and the lowest surface roughness at the highest deposition rate. We demonstrate how increasing the substrate bias voltage leads to a highly textured film. The preferred orientation of the film changes from (111) to (200) as the substrate bias voltage is increased. An X-ray pole scan shows that the (111) plane grows parallel to the SiO2 substrate when the substrate is grounded while it is gradually replaced by the (200) plane as the substrate bias voltage is increased up to −200 V. The lowest electrical resistivity is measured as 48.4 μΩ cm for the VN film deposited under substrate bias of −50 V. This is among the lowest room temperature values that have been reported for a VN film. We found that the nitrogen concentration presents a decline by 6.5 percentage points as the substrate bias is changed from ground to −200 V.
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| 16. |
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| 17. |
- Ingvarsson, Henrik, et al.
(författare)
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Crystallization of Mycobacterium smegmatis methionyl-tRNA synthetase in the presence of methionine and adenosine
- 2009
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Ingår i: Acta Crystallographica. Section F. - 1744-3091 .- 1744-3091. ; 65:Part 6, s. 618-620
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Tidskriftsartikel (refereegranskat)abstract
- Methionyl-tRNA synthetase (MetRS) from Mycobacterium smegmatis was recombinantly expressed in Escherichia coli and purified using Ni(2+)-affinity and size-exclusion chromatography. Crystals formed readily in the presence of the ligands methionine and adenosine. These two ligands are components of an intermediate in the two-step catalytic mechanism of MetRS. The crystals were produced using the vapour-diffusion method and a full data set to 2.1 A resolution was collected from a single crystal. The crystal belonged to the monoclinic space group C2, with unit-cell parameters a = 155.9, b = 138.9, c = 123.3 A, beta = 124.8 degrees . The presence of three molecules in the asymmetric unit corresponded to a solvent content of 60% and a Matthews coefficient of 3.1 A(3) Da(-1). Structure determination is in progress.
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| 18. |
- Ingvarsson, Magdalena, et al.
(författare)
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Isolation and culture of ovarian tumour cells, cytological and cell survival evaluation
- 1999
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 19:6B, s. 5069-5073
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the reproducibility and reliability of the fluorometric microculture cytotoxicity assay (FMCA). Emphasis was placed on obtaining pure tumour cell cultures which were subjected to careful cytological evaluation. Preparations of 39 ovarian tumours, malignant, borderline and benign were made, of which 37 were successfully cultured. In 34 of the 37 tumour cell cultures, the epithelial cell fraction was > 90%, and in 30 of 39 cultures the epithelial cell fraction was > 95%. Transportation within 24 h and the 72 h incubation did not change the yield or epithelial cell fraction. There was a linear relationship between fluorescence and the number of viable cells. The fluorescence increased with time, making only comparisons within each assay plate possible. The sensitivity of the method makes it possible to perform many analyses on a small amount of material. The method also makes it possible to study cells derived from all stages of the disease, including benign tumours.
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| 19. |
- Ingvarsson, T, et al.
(författare)
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Assessment of primary hip osteoarthritis: comparison of radiographic methods using colon radiographs : comparison of radiographic methods using colon radiographs
- 2000
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 59:8, s. 650-653
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the reliability of quantitative measurement of minimum hip joint space with a qualitative global assessment of radiological features for estimating the prevalence of primary osteoarthritis (OA) of the hip in colon radiographs.METHODS: All colon radiographs from patients aged 35 or older, taken at three different radiographic departments in Iceland during the years 1990-96, were examined. A total of 3002 hips in 638 men and 863 women were analysed. Intraobserver and interobserver reliability was assessed by measuring 147 randomly selected radiographs (294 hips) twice by the same observer, and 87 and 98 randomly selected radiographs (174 and 196 hips) by two additional independent observers. Minimum hip joint space was measured with a millimetre ruler, and global assessment of radiological features by a published atlas.RESULTS: With a minimum joint space of 2.5 mm or less as definition for OA, 212 hips were defined as having OA. When the global Kellgren and Lawrence assessment with grade 2 (definite narrowing in the presence of definite osteophytes) or higher as definition for OA was used, 202 hips showed OA. However, only 166 hips were diagnosed as OA with both systems. With 2.0 or 3.0 mm minimum joint space as cut off point, the difference between the two methods increased. Both intrarater and interrater reliability was significantly higher with joint space measurement than with global assessment.CONCLUSIONS: Overall prevalence of radiological OA was similar with the two methods. However, the quantitative measurement of minimum hip joint space had a better within-observer and between-observer reliability than qualitative global assessment of radiographic features of hip OA. It is thus suggested that minimum joint space measurement is a preferable method in epidemiological studies of radiological hip OA.
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| 20. |
- Ingvarsson, T, et al.
(författare)
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Long-term results after adolescent Blount's disease
- 1997
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Ingår i: Journal of Pediatric Orthopaedics Part B. - 1060-152X. ; 6:2, s. 6-153
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Tidskriftsartikel (refereegranskat)abstract
- A long-term follow-up study was made of 23 patients with an average age of 47 years (range 38-68 years) who had adolescent Blount's disease. Four patients had bilateral disease (27 affected knees). Nine knees had no treatment during childhood, 11 were treated by physiodesis, and seven were treated by osteotomy of the proximal tibia. At follow-up, most of the patients had no pain or mild pain from their knee. Nine knees showed arthrosis. We conclude that most children with adolescent Blount's disease will have a straight leg at middle age without arthrosis and that this result can be obtained in one of four patients without treatment.
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| 21. |
- Ingvarsson, T, et al.
(författare)
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Long-term results after infantile Blount's disease
- 1998
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Ingår i: Journal of Pediatric Orthopaedics Part B. - 1060-152X. ; 7:3, s. 9-226
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Tidskriftsartikel (refereegranskat)abstract
- A long-term follow-up of 49 patients with an average age of 38 years (range: 25-67 years) who had experienced infantile Blount's disease was done. Thirty-seven patients had bilateral disease, giving a total of 86 affected knees. Thirty-eight knees had conservative or no treatment during childhood; 13 were treated by epiphysiodesis, and 35 by osteotomy. At follow-up, 11 knees showed arthrosis, and 9 were graded as mild. Ten knees had been surgically treated by medial meniscectomy at an average age of 29 years (range: 19-45 years), after the diagnosis of Blount's disease. Four of the knees showed arthrosis. Most of the patients had a straight leg and mild or no pain from their knee. It is concluded that most children with infantile Blount's disease will, at the age of 40 years, have a straight leg without arthrosis and that one third can reach this result without any treatment.
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| 22. |
- Price, Douglas T., et al.
(författare)
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Origins of inhabitants from the 16th century Sala (Sweden) silver mine cemetery – A lead isotope perspective
- 2017
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403. ; 80, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Historical documents record the operation of a silver mine from the 16th century AD located near the former village of Salberget in central Sweden. The historical record describes several categories of inhabitants, including local families, workers and miners, foreign engineers and mining specialists, as well as war captives and criminals used as forced labor in the mines. A church yard in the vicinity of the village served as a burial ground. Archaeological evidence indicates two distinct grave types (coffin and earthen) and physical anthropology documents differences in age and sex between these grave types, as well as harsh conditions of life. Strontium and oxygen isotopes have been used previously to investigate the place of origin of the cemetery inhabitants and clear differences among the types of graves were seen in the isotope results. Place of origin was more difficult to ascertain however. Here we utilize lead isotopes as an additional isotopic tracer to identify origins. The lead isotope investigations pinpoint several areas outside of the Sala region where some of the inhabitants originated. In addition, the study documents the benefits of using lead isotopes in human proveniencing studies.
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| 23. |
- Riehl, Jennifer F. L., et al.
(författare)
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Genomic and transcriptomic analyses reveal polygenic architecture for ecologically important traits in aspen (Populus tremuloides Michx.)
- 2023
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Intraspecific genetic variation in foundation species such as aspen (Populus tremuloides Michx.) shapes their impact on forest structure and function. Identifying genes underlying ecologically important traits is key to understanding that impact. Previous studies, using single-locus genome-wide association (GWA) analyses to identify candidate genes, have identified fewer genes than anticipated for highly heritable quantitative traits. Mounting evidence suggests that polygenic control of quantitative traits is largely responsible for this “missing heritability” phenomenon. Our research characterized the genetic architecture of 30 ecologically important traits using a common garden of aspen through genomic and transcriptomic analyses. A multilocus association model revealed that most traits displayed a highly polygenic architecture, with most variation explained by loci with small effects (likely below the detection levels of single-locus GWA methods). Consistent with a polygenic architecture, our single-locus GWA analyses found only 38 significant SNPs in 22 genes across 15 traits. Next, we used differential expression analysis on a subset of aspen genets with divergent concentrations of salicinoid phenolic glycosides (key defense traits). This complementary method to traditional GWA discovered 1243 differentially expressed genes for a polygenic trait. Soft clustering analysis revealed three gene clusters (241 candidate genes) involved in secondary metabolite biosynthesis and regulation. Our work reveals that ecologically important traits governing higher-order community- and ecosystem-level attributes of a foundation forest tree species have complex underlying genetic structures and will require methods beyond traditional GWA analyses to unravel.
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| 24. |
- Styrkarsdottir, Unnur, et al.
(författare)
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GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10 −42 , β = −0.090) and confers risk of hip fracture (P = 1.0 × 10 −8 , OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
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| 25. |
- Sultan, M. T., et al.
(författare)
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Photoluminescence study of Si1-xGex nanoparticles in various oxide matrices
- 2021
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Ingår i: 2021 International Semiconductor Conference (Cas). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 21-24
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Konferensbidrag (refereegranskat)abstract
- We investigate the photoluminescence properties of structures comprising of Si1-xGex nanoparticles (NPs) within SiO2, GeO2, TiO2 and Ta2O5 oxide matrices. Of the investigated structures, it was observed that the structures with GeO2 and TiO2 matrices provide increased spectral response (at similar to 907 and 844 nm respectively) and increased PL intensity. The improved PL characteristic have been attributed to increased diffusion barrier against oxygen which otherwise would result in formation of unwanted oxide at the film-oxide interface, thereby deteriorating the optical properties.
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