| 1. |
- Reinke, Beth A, et al.
(författare)
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Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1459-1466
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Tidskriftsartikel (refereegranskat)abstract
- Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.
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| 2. |
- 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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| 3. |
- Bainbridge, Matthew N, et al.
(författare)
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Germline mutations in shelterin complex genes are associated with familial glioma
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 107:1
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Tidskriftsartikel (refereegranskat)abstract
- Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.
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| 4. |
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| 5. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 6. |
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| 7. |
- Jalali, Ali, et al.
(författare)
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Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5, s. 8278-
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Tidskriftsartikel (refereegranskat)abstract
- Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.
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| 8. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 9. |
- Ostrom, Quinn T., et al.
(författare)
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Evaluating glioma risk associated with extent of European admixture in African-Americans and Latinos
- 2018
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 78:13
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Glioma incidence is highest in non-Hispanic Whites, where it occurs ~2x as frequently compared with other race/ethnicity groups. Glioma GWAS to date have included European ancestry populations only, and it is unknown whether variants identified by these analyses are associated with glioma in non- European ancestry populations. African Americans and Hispanics are admixed populations with varying proportions of European ancestry. While global ancestry may be similar within admixed groups, the proportion of European ancestry at each allele can vary across the genome. As glioma is more common in European ancestry populations, the presence of increased local European ancestry in these admixed populations could be used to identify glioma risk loci. Here we assessed whether excess European ancestry at established risk loci (Melin et al, Nature Genetics, 2017) was associated with glioma risk in non-European ancestry populations. Global ancestry was estimated using fastStructure, and local ancestry was estimated using RFMix. Both methods used 1,000 genomes project reference populations (African: YRI; European: CEU; East Asian: CHB/JPT; and Native American: CLM/PEL/MXL). We evaluated differences in local European ancestry between cases and controls using logistic regression conditioned on global European ancestry within 500kb of 25 previously identified risk variants among individuals with ≥50% African ancestry, and ≥30% Native American ancestry for all gliomas, and for grade IV glioblastoma (GBM) and grade II-III non-GBM. There were 347 individuals (184 cases and 163 controls) with ≥50% global African ancestry, and 277 individuals (153 cases and 124 controls) with ≥30% global American ancestry. There was no significant difference in proportion of global European ancestry between cases and controls with ≥50% global African ancestry (cases: 18.2%, controls: 17.7%, p=0.6834), and no significant difference in proportion of global European ancestry between cases and controls with ≥30% global American ancestry (cases: 51.1%, controls: 49.0%, p=0.2123). Among individuals with >50% African ancestry, we observed a nominally significant association between all glioma and increased local European ancestry at 7p11.2 (EGFR, pmin=0.0070) and between GBM and increased local European ancestry at 22q13.1 (CSNK1E, pmin=0.0098), both near SNPs previously associated with glioblastoma in majority European-ancestry populations. The dataset used for this analysis represents the largest collection of genotyped non-European glioma cases. These results suggest that glioma risk in African Americans may be associated with an increased local European ancestry variants at glioma risk loci previously identified in majority European ancestry populations (7p11.2 and 22q13.1).
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| 10. |
- Ostrom, Quinn T., et al.
(författare)
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Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:3, s. 739-748
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Tidskriftsartikel (refereegranskat)abstract
- Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have <80% EA, or self-identify as non-White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with >= 40% AA (AFR(>= 0.4)), and >= 15% NAA (AMR(>= 0.15)), genome-wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 x 10(-4); 11p11.12, p = 7.0 x 10-4) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR(>= 0.4). In addition, we identified a peak at rs1620291 (p = 4.36 x 10(-6)) in 7q21.3. Among AMR(>= 0.15), we found an association between increased EA in one region (12q24.21, p = 8.38 x 10(-4)), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 x 10(-4)). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies. What's new? Glioma is rare in non-White populations, and most glioma genome-wide association studies have included only primarily European ancestry populations. Here, the authors assess whether variation in European ancestry is associated with glioma risk in populations with a combination of European, African and Native American ancestry. Based on African American and Hispanic cases from two large glioma case-control studies, this analysis shows that increased European ancestry in admixed populations may be associated with increased glioma risk. The associations between glioma and two chromosomal regions previously identified in European ancestry populations, and four novel regions, may guide future studies.
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| 11. |
- Pennington, Bruce, et al.
(författare)
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Individual prediction of dyslexia by single vs. multiple deficit models.
- 2012
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Ingår i: Journal of Abnormal Psychology. - : American Psychological Association. - 0021-843X .- 1939-1846. ; 121:1, s. 212-224
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Tidskriftsartikel (refereegranskat)abstract
- The overall goals of this study were to test single versus multiple cognitive deficit models of dyslexia (reading disability) at the level of individual cases and to determine the clinical utility of these models for prediction and diagnosis of dyslexia. To accomplish these goals, we tested five cognitive models of dyslexia-two single-deficit models, two multiple-deficit models, and one hybrid model-in two large population-based samples, one cross-sectional (Colorado Learning Disability Research Center) and one longitudinal (International longitudinal Twin Study). The cognitive deficits included in these cognitive models were in phonological awareness, language skill, and processing speed and/or naming speed. To determine whether an individual case fit one of these models, we used two methods: 1) the presence or absence of the predicted cognitive deficits, and 2) whether the individuals level of reading skill best fit the regression equation with the relevant cognitive predictors (i.e., whether their reading skill was proportional to those cognitive predictors.) We found that roughly equal proportions of cases met both tests of model fit for the multiple deficit models (30-36%) and single deficit models (24-28%); hence, the hybrid model provided the best overall fit to the data. The remaining roughly 40% of cases in each sample lacked the deficit or deficits that corresponded with their best-fitting regression model. We discuss the clinical implications of these results for both diagnosis of school-age children and preschool prediction of children at risk for dyslexia.
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| 12. |
- Richard, Benjamin, et al.
(författare)
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Characterization of the conformational alterations, reduced anticoagulant activity, and enhanced antiangiogenic activity of prelatent antithrombin
- 2008
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 283:21, s. 14417-14429
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Tidskriftsartikel (refereegranskat)abstract
- A conformationally altered prelatent form of antithrombin that possesses both anticoagulant and antiangiogenic activities is produced during the conversion of native to latent antithrombin (Larsson, H., Akerud, P., Nordling, K., Raub-Segall, E., Claesson-Welsh, L., and Björk, I. (2001) J. Biol. Chem. 276, 11996-12002). Here, we show that the previously characterized prelatent antithrombin is a mixture of native antithrombin and a modified, true prelatent antithrombin that are resolvable by heparin-agarose chromatography. Kinetic analyses revealed that prelatent antithrombin is an intermediate in the conversion of native to latent antithrombin whose formation is favored by stabilizing anions of the Hofmeister series. Purified prelatent antithrombin had reduced anticoagulant function compared with native antithrombin, due to a reduced heparin affinity and consequent impaired ability of heparin to either bridge prelatent antithrombin and coagulation proteases in a ternary complex or to induce full conformational activation of the serpin. Significantly, prelatent antithrombin possessed an antiangiogenic activity more potent than that of latent antithrombin, based on the relative abilities of the two forms to inhibit endothelial cell growth. The prelatent form was conformationally altered from native antithrombin as judged from an attenuation of tryptophan fluorescence changes following heparin activation and a reduced thermal stability. The alterations are consistent with the limited structural changes involving strand 1C observed in a prelatent form of plasminogen activator inhibitor-1 (Dupont, D. M., Blouse, G. E., Hansen, M., Mathiasen, L., Kjelgaard, S., Jensen, J. K., Christensen, A., Gils, A., Declerck, P. J., Andreasen, P. A., and Wind, T. (2006) J. Biol. Chem. 281, 36071-36081), since the (1)H NMR spectrum, electrophoretic mobility, and proteolytic susceptibility of prelatent antithrombin most resemble those of native rather than those of latent antithrombin. Together, these results demonstrate that limited conformational alterations of antithrombin that modestly reduce anticoagulant activity are sufficient to generate antiangiogenic activity.
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| 13. |
- 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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| 14. |
- Amirian, E. Susan, et al.
(författare)
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Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk : a report from the Glioma International Case-Control Study
- 2016
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 25:2, s. 282-290
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. Methods: The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Results: Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. Conclusion: A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. Impact: As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. (C) 2016 AACR.
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| 15. |
- Amirian, E. Susan, et al.
(författare)
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Aspirin, NSAIDs, and Glioma Risk : Original Data from the Glioma International Case-Control Study and a Meta-analysis
- 2019
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:3, s. 555-562
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Tidskriftsartikel (refereegranskat)abstract
- Background: There have been few studies of sufficient size to address the relationship between glioma risk and the use of aspirin or NSAIDs, and results have been conflicting. The purpose of this study was to examine the associations between glioma and aspirin/NSAID use, and to aggregate these findings with prior published studies using meta-analysis.Methods: The Glioma International Case-Control Study (GICC) consists of 4,533 glioma cases and 4,171 controls recruited from 2010 to 2013. Interviews were conducted using a standardized questionnaire to obtain information on aspirin/NSAID use. We examined history of regular use for ≥6 months and duration-response. Restricted maximum likelihood meta-regression models were used to aggregate site-specific estimates, and to combine GICC estimates with previously published studies.Results: A history of daily aspirin use for ≥6 months was associated with a 38% lower glioma risk, compared with not having a history of daily use [adjusted meta-OR = 0.62; 95% confidence interval (CI), 0.54–0.70]. There was a significant duration-response trend (P = 1.67 × 10−17), with lower ORs for increasing duration of aspirin use. Duration-response trends were not observed for NSAID use. In the meta-analysis aggregating GICC data with five previous studies, there was a marginally significant association between use of aspirin and glioma (mOR = 0.84; 95% CI, 0.70–1.02), but no association for NSAID use.Conclusions: Our study suggests that aspirin may be associated with a reduced risk of glioma.Impact: These results imply that aspirin use may be associated with decreased glioma risk. Further research examining the association between aspirin use and glioma risk is warranted.
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| 16. |
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| 17. |
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| 18. |
- Amirian, E. Susan, et al.
(författare)
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The Glioma International Case-Control Study : A Report From the Genetic Epidemiology of Glioma International Consortium
- 2016
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 183:2, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.
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| 19. |
- Andersson, Ulrika, et al.
(författare)
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Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer
- 2014
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 16:10, s. 1333-1340
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer. The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.
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| 20. |
- Arnett, Anne, et al.
(författare)
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A cross-lagged model of the development of ADHD inattention symptoms and rapid naming speed
- 2012
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Ingår i: Journal of Abnormal Child Psychology. - : Springer. - 0091-0627 .- 1573-2835. ; 40:8, s. 1313-1326
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Tidskriftsartikel (refereegranskat)abstract
- Although previous research has identified contemporaneous associations between cognitive deficits and symptom phenotypes in Attention Deficit/Hyperactivity Disorder, no studies have as yet attempted to identify direction of effect. The present study used cross-lagged path modeling to examine competing hypotheses about longitudinal associations between rapid naming speed and symptoms of inattention in children. 1,506 school-age twins from Australia and the U.S. were tested for inattention, hyperactivity/impulsivity, and rapid naming speed at three and four time points, respectively. Symptom severity of inattention from Kindergarten to fourth grade is consistently predicted by previous rapid naming, over and above auto-regressive and correlational associations in the model. Likewise, inattention symptoms have a small but significant predictive effect on subsequent rapid naming. The findings support a reciprocal relationship between naming speed and ADHD inattentive symptoms.
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| 21. |
- Arnett, Anett, et al.
(författare)
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The SWAN captures variance at the negative and positive ends of the ADHD Symptom dimension
- 2013
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Ingår i: Journal of Attention Disorders. - : Sage Publications. - 1087-0547 .- 1557-1246. ; 17:2, s. 152-162
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Strengths and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN) Rating Scale differs from previous parent reports of ADHD in that it was designed to also measure variability at the positive end of the symptom spectrum. Method: The psychometric properties of the SWAN were tested and compared with an established measure of ADHD, the Disruptive Behavior Rating Scale (DBRS). Results: The SWAN demonstrates comparable validity, reliability, and heritability to the DBRS. Furthermore, plots of the SWAN and DBRS reveal heteroscedasticity, which supports the SWAN as a preferred measure of positive attention and impulse regulation behaviors. Conclusion: The ability of the SWAN to measure additional variance at the adaptive end of the ADHD symptom dimensions makes it a promising tool for behavioral genetic studies of ADHD.
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| 22. |
- Atkins, Isabelle, et al.
(författare)
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Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma
- 2019
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 79:8, s. 2065-2071
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM and 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P < 5.69 x 10(-6), candidate novel risk locus for GBM (mean Z = 4.43; P = 5.68 x 10(-6)). GALNT6 resides at least 55 Mb away from any previously identified glioma risk variant, while all other 30 significantly associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis.Significance: This study identifies new genes associated with glioma risk, increasing understanding of how these tumors develop.
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| 23. |
- Berntsson, Shala G., 1964-, et al.
(författare)
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Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study.
- 2018
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 265:6, s. 1432-1442
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls.The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n=4533) and controls (n=4171) were also asked about seizures less than 2years from diagnosis and previous seizure history more than 2years prior to tumor diagnosis, including childhood seizures.Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p<0.009). No significant difference was found between glioma cases and controls in terms of seizure occurring more than 2 years before diagnosis or during childhood.Our study showed that glioma-related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma.
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| 24. |
- Brian, Byrne, et al.
(författare)
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Evolutionary and genetic perspectives on educational attainment
- 2010. - 1
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Ingår i: International handbook of psychology in education. - Bingley : Emerald Publishing Limited. - 9781848552326 ; , s. 3-33
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- "The International Handbook of Psychology in Education" provides researchers, practitioners and advisers working in the fields of psychology and education with an overview of cutting-edge research across a broad spectrum of work within the domain of psychology of education. The chapters in the handbook are authored by internationally recognised researchers, from across Europe, North America and the Pacific Rim. As well as covering the latest thinking within established areas of enquiry, the handbook includes chapters on recently emerging, yet important, topics within the field and explicitly considers the inter-relationship between theory and practice. A strong unifying theme is the volume's emphasis on processes of teaching and learning. The work discussed in the handbook focuses on typically developing school-age children, although issues relating to specific learning difficulties are also addressed.
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| 25. |
- Byrne, Brian, et al.
(författare)
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A behaviour-genetic analysis of orthographic learning, spelling and decoding
- 2008
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Ingår i: Journal of research in reading (Print). - : Wiley. - 0141-0423 .- 1467-9817. ; 31:1
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Tidskriftsartikel (refereegranskat)abstract
- As part of a longitudinal twin study of literacy and language, we conducted a behaviour-genetic analysis of orthographic learning, spelling and decoding in Grade 2 children (225 identical and 214 fraternal twin pairs) in the United States and Australia. Each variable showed significant genetic and unique environment influences. Multivariate analyses revealed very high genetic correlations among the variables, indicating that the same genes are involved in their aetiology. These genes are partly independent of those contributing to intelligence. A further analysis indicated that the covariation between decoding and orthographic learning is mediated by shared genes rather than by a direct causal path. The authors argue that a learning parameter, most directly assessed by orthographic learning in this study, underlies all three literacy variables. The results are also discussed in relation to Share's self-teaching hypothesis, which may require modification. © United Kingdom Literacy Association 2008.
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| 26. |
- Byrne, Brian, et al.
(författare)
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Behavior-genetic studies of academic performance in school students : A commentary for professional in psychology and education
- 2019. - 1
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Ingår i: Reading development and difficulties. - Cham : Springer. - 9783030265496 - 9783030265502 ; , s. 213-232
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Bokkapitel (refereegranskat)abstract
- Available behavior-genetic research indicates that the single largest factor influencing individual differences in literacy development is genetic endowment. We briefly review some typical evidence and methodology used in studying the behavior-genetics of reading. We then outline three hypothetical educational scenarios and demonstrate how behavior-genetic studies might play out in them, with the aim of enhancing the critical capacity of school psychologists and other educational professionals to evaluate research findings in this area. We show that heritability estimates will tend to be higher in educational environments in which the instruction and other factors are more uniform, that the way subsamples are combined can affect estimates, and that population-level estimates cannot be used to determine the etiology of any individual child’s performance. We address and dismiss genetic determinism, and review evidence to suggest that genetic accounts of reading disability may reduce blame and stigma yet increase pessimism about successful intervention. However, we argue that continued research into optimal ways to design and deliver curricula is quite compatible with the substantial heritability of individual differences in literacy and has already provided grounds for optimism. We also suggest that genetically derived constraints on academic progress bring into sharp focus questions about the goals of education.
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| 27. |
- Byrne, Brian, et al.
(författare)
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Dyslexia
- 2014
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Ingår i: The Routledge international companion to educational psychology. - London : Routledge. - 9780415675581 - 9780415675604 ; , s. 297-306
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Byrne, Brian, et al.
(författare)
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Genetic and environmental influences on aspects of literacy and language in early childhood : Continuity and change from preschool to Grade 2
- 2009
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Ingår i: JOURNAL OF NEUROLINGUISTICS. - : Elsevier BV. - 0911-6044. ; 22:3, s. 219-236
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Tidskriftsartikel (refereegranskat)abstract
- Early literacy and language skills of twin children in the USA, Australia, and Scandinavia were explored in a genetically sensitive design (maximum N = 615 pairs). For this article, we report aspects of preschool and Grade 2 data. In Grade 2, there were strong genetic influences on word reading, reading comprehension, and spelling. Vocabulary was about equally affected by genes and shared environment. Multivariate analyses indicated substantial genetic overlap among the Grade 2 literacy variables. Longitudinal analyses showed that genetic factors evident at the preschool stage continued to affect literacy and vocabulary three years later in Grade 2, but there was also evidence of new genetic factors coming into play over the time interval, at least for literacy. Suggestions are made about the search for underlying biological and cognitive processes, and educational implications are explored.
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| 29. |
- Byrne, Brian, et al.
(författare)
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Genetic and environmental influences on early literacy
- 2006
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Ingår i: Journal of research in reading (Print). - : Wiley. - 0141-0423 .- 1467-9817. ; 29:1, s. 33-49
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Tidskriftsartikel (refereegranskat)abstract
- Prereading and early reading skills of preschool twin children in Australia, Scandinavia and the United States were explored in a genetically sensitive design (max. N = 627 preschool pairs and 422 kindergarten pairs). Analyses indicated a strong genetic influence on preschool phonological awareness, rapid naming and verbal memory. Print awareness, vocabulary and grammar/morphology were subject primarily to shared environment effects. There were significant genetic and shared environment correlations among the preschool traits. Kindergarten reading, phonological awareness and rapid naming were primarily affected by genes, and spelling was equally affected by genes and shared environment. Multivariate analyses revealed genetic and environmental overlap and independence among kindergarten variables. Longitudinal analyses showed genetic continuity as well as change in phonological awareness and rapid naming across the 2 years. Relations among the preschool variables of print awareness, phonological awareness and rapid naming and kindergarten reading were also explored in longitudinal analyses. Educational implications are discussed. © United Kingdom Literacy Association 2006.
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| 30. |
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| 31. |
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| 32. |
- Byrne, Brian, et al.
(författare)
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Longitudinal twin study of early literacy development : Preschool and kindergarten phases
- 2005
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Ingår i: Scientific Studies of Reading. - : Informa UK Limited. - 1088-8438 .- 1532-799X. ; 9:3, s. 219-235
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Tidskriftsartikel (refereegranskat)abstract
- We conducted behavior-genetic analyses of kindergarten reading, spelling, phonological awareness, rapid naming, and spoken sentence processing in 172 pairs of monozygotic and 153 pairs of same-sex dizygotic twin kindergarten children sampled in the United States and Australia. We also modeled progress from preschool to kindergarten in literacy-related variables, with larger numbers of twins contributing to the preschool phase. Reading, phonological awareness, and rapid naming at kindergarten showed substantial effects of genes and modest effects of shared environment, spelling was influenced by genes and environment equally, and sentence processing was affected primarily by shared environment. Longitudinal analyses indicated that the same genes affect phonological awareness in preschool and kinder garten but that a new genetic factor comes into play in rapid naming as letters and digits are introduced in kindergarten. At preschool, print knowledge and phonological awareness share one source of genetic influence, which in turn affects reading and spelling in kindergarten. Phonological awareness is subject to a second genetic factor, but only the one it shares with print also influences kindergarten reading and spelling. In contrast to the genetic effects, a single source of shared environment affects preschool print knowledge and phonological awareness and kindergarten reading. The results are discussed in the context of theoretical and practical issues in literacy development. Copyright © 2005, Lawrence Erlbaum Associates, Inc.
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| 33. |
- Byrne, Brian, et al.
(författare)
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Longitudinal twin study of early literacy development : Preschool through Grade 1
- 2007
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Ingår i: Reading and writing. - : Springer Science and Business Media LLC. - 0922-4777 .- 1573-0905. ; 20:1-2, s. 77-102
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Tidskriftsartikel (refereegranskat)abstract
- Grade 1 literacy skills of twin children in Australia (New South Wales) and the United States (Colorado) were explored in a genetically sensitive design (N = 319 pairs). Analyses indicated strong genetic influence on word and nonword identification, reading comprehension, and spelling. Rapid naming showed more modest, though reliable, genetic influence. Phonological awareness was subject to high nonshared environment and no reliable genetic effects, and individual measures of memory and learning were also less affected by genes than nonshared environment. Multivariate analyses showed that the same genes affected word identification, reading comprehension, and spelling. Country comparisons indicated that the patterns of genetic influence on reading and spelling in Grade 1 were similar, though for the U.S. but not the Australian children new genes came on stream in the move from kindergarten to Grade 1. We suggest that this is because the more intensive kindergarten literacy curriculum in New South Wales compared with Colorado, consistent with the mean differences between the two countries, means that more of the genes are "online" sooner in Australia because of accelerated overall reading development. © Springer Science+Business Media B.V. 2007.
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| 34. |
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| 35. |
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| 36. |
- Byrne, Brian, et al.
(författare)
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Multivariate genetic analysis of learning and early reading development
- 2013
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Ingår i: Scientific Studies of Reading. - : Routledge. - 1088-8438 .- 1532-799X. ; 17:3, s. 224-242
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Tidskriftsartikel (refereegranskat)abstract
- The genetic factor structure of a range of learning measures was explored in twin children, recruited in preschool and followed to Grade 2 (N = 2,084). Measures of orthographic learning and word reading were included in the analyses to determine how these patterned with the learning processes. An exploratory factor analysis of the genetic correlations among the variables indicated a three-factor model. Vocabulary tests loaded on the first factor, the Grade 2 measures of word reading and orthographic learning, plus preschool letter knowledge, loaded on the second, and the third was characterized by tests of verbal short-term memory. The three genetic factors correlated, with the second (print) factor showing the most specificity. We conclude that genetically influenced learning processes underlying print–speech integration, foreshadowed by preschool letter knowledge, have a degree of independence from genetic factors affecting spoken language. We also argue that the psychology and genetics of associative learning be afforded a more central place in studies of reading (dis)ability and suggest some links to molecular studies of the genetics of learning.
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| 37. |
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| 38. |
- Byrne, Brian, et al.
(författare)
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Reading and reading acquisition in European languages
- 2014
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Ingår i: South and Southeast Asian psycholinguistics. - Cambridge : Cambridge University Press. - 9781107017764 ; , s. 159-170
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 39. |
- Byrne, Brian, et al.
(författare)
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Teacher Effects in Early Literacy Development: Evidence From a Study of Twins
- 2010
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Ingår i: Journal of Educational Psychology. - : Apa American Psychological Association. - 0022-0663 .- 1939-2176. ; 102:1, s. 32-42
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Tidskriftsartikel (refereegranskat)abstract
- It is often assumed that differences in teacher characteristics area major source of variability in childrens educational achievements. We examine this assumption for early literacy achievement by calculating the correlations between pairs of twin children who either shared or did not share a teacher in kindergarten, Grade 1, and Grade 2. Teacher effects-or, more strictly, classroom effects-would show up as higher correlations for same-class than for different-class twin pairs. Same-class correlations were generally higher than different-class correlations.. though not significantly so on most occasions. On the basis of the results, we estimate that the maximum variance accounted for by being assigned to the same or different classrooms is 8%. This is an upper-bound figure for a teacher effect because factors other than teachers may contribute to variation attributable to classroom assignment. We discuss the limitations of the study and draw out some of its educational implications.
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| 40. |
- Byrne, Brian, et al.
(författare)
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The longitudinal perspective on developmental disorders
- 2012. - 1
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Ingår i: Current issues in developmental disorders. - Hove : Psychology Press. - 9781848720848 ; , s. 73-92
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- "Cognitive development in children is a highly complex process which, while remarkably resilient, can be disrupted in a variety of ways. This volume focuses on two types of neurodevelopmental disorder: syndromic conditions, such as fragile X syndrome, Down syndrome, Williams syndrome and Velocardiofacial syndrome; and non-syndromic conditions including dyslexia, specific language impairment, autism spectrum disorder and attention deficit hyperactivity disorder. This book provides a state-of-the-art review of current research and covers key topics across the full range of developmental disorders. Topics covered include: diagnosis and comorbidity genetics longitudinal studies computational models distinguishing disorder from deprivation/delay language and culture the history of research into developmental disorders The book also looks at how the study of developmental disorders has contributed to our understanding of typical development, and themes emerge that are common across chapters, including intervention and education, and the neurobiological bases of developmental disorders. The result is a fascinating and thought-provoking volume that will be indispensable to advanced students, researchers and practitioners in the fields of developmental psychology, neuropsychology, speech and language therapy and other developmental disorders"--
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| 41. |
- Christopher, Micaela, et al.
(författare)
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Genetic and environmental etiologies of the longitudinal relations between prereading skills and reading
- 2015
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Ingår i: Child Development. - : Wiley. - 0009-3920 .- 1467-8624. ; 86:2, s. 342-361
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Tidskriftsartikel (refereegranskat)abstract
- The present study explored the environmental and genetic etiologies of the longitudinal relations between prereading skills and reading and spelling. Twin pairs (n = 489) were assessed before kindergarten (M = 4.9 years), post-first grade (M = 7.4 years), and post-fourth grade (M = 10.4 years). Genetic influences on five prereading skills (print knowledge, rapid naming, phonological awareness, vocabulary, and verbal memory) were primarily responsible for relations with word reading and spelling. However, relations with post-fourth-grade reading comprehension were due to both genetic and shared environmental influences. Genetic and shared environmental influences that were common among the prereading variables covaried with reading and spelling, as did genetic influences unique to verbal memory (only post-fourth-grade comprehension), print knowledge, and rapid naming.
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| 42. |
- Christopher, Micaela, et al.
(författare)
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Modeling the etiology of individual differences in early reading development : Evidence for strong genetic influences
- 2013
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Ingår i: Scientific Studies of Reading. - : Routledge. - 1088-8438 .- 1532-799X. ; 17:5, s. 350-368
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Tidskriftsartikel (refereegranskat)abstract
- We explored the etiology of individual differences in reading development from post-kindergarten to post–4th grade by analyzing data from 487 twin pairs tested in Colorado. Data from three reading measures and one spelling measure were fit to biometric latent growth curve models, allowing us to extend previous behavioral genetic studies of the etiology of early reading development at specific time points. We found primarily genetic influences on individual differences at post–1st grade for all measures. Genetic influences on variance in growth rates were also found, with evidence of small, nonsignificant, shared environmental influences for two measures. We discuss our results, including their implications for educational policy.
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| 43. |
- Christopher, Micaela, et al.
(författare)
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The genetic and environmental etiologies of individual differences in early reading growth in Australia, the United States and Scandinavia
- 2013
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Ingår i: Journal of experimental child psychology (Print). - : Elsevier. - 0022-0965 .- 1096-0457. ; 115:3, s. 453-467
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Tidskriftsartikel (refereegranskat)abstract
- This first cross-country twin study of individual differences in reading growth from post-kindergarten to post-second grade analyzed data from 487 twin pairs from the United States, 267 twin pairs from Australia, and 280 twin pairs from Scandinavia. Data from two reading measures were fit to biometric latent growth models. Individual differences for the reading measures at post-kindergarten in the United States and Australia were due primarily to genetic influences and to both genetic and shared environmental influences in Scandinavia. In contrast, individual differences in growth generally had large genetic influences in all countries. These results suggest that genetic influences are largely responsible for individual differences in early reading development. In addition, the timing of the start of formal literacy instruction may affect the etiology of individual differences in early reading development but have only limited influence on the etiology of individual differences in growth.
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| 44. |
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| 45. |
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| 46. |
- Deyhle, Richard T, et al.
(författare)
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Maintenance of near normal bone mass and architecture in lethally irradiated female mice following adoptive transfer with as few as 750 purified hematopoietic stem cells
- 2019
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Ingår i: Radiation Research. - 0033-7587. ; 5, s. 413-427
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Tidskriftsartikel (refereegranskat)abstract
- Total-body irradiation (TBI) followed by transfer of bone marrow cells from donors is routinely performed in immunology research and can be used to manipulate differentiation and/or function of bone cells. However, exposure to high-dose radiation can result in irreversible osteopenia, and transfer of heterogeneous cell populations can complicate interpretation of results. The goal of this research was to establish an approach for reconstituting bone marrow using small numbers of purified donor-derived hematopoietic stem cells (HSCs) without negatively affecting bone metabolism. Gamma-irradiated (9 Gy) WBB6F1 mice were engrafted with bone marrow cells (5 × 106 cells) or purified HSCs (3,000 cells) obtained from GFP transgenic mice. In vivo analysis and in vitro differentiation assays performed two months later established that both methods were effective in reconstituting the hematopoietic compartment with donor-derived cells. We confirmed these findings by engrafting C57Bl/6 (B6) mice with bone marrow cells or purified HSCs from CD45.1 B6 congenic mice. We next performed adoptive transfer of purified HSCs (750 cells) into WBB6F1 and radiosensitive KitW/W-v mice and evaluated the skeleton two months later. Minimal differences were observed between controls and WBB6F1-engrafted mice that received fractionated doses of 2 × 5 Gy. Kitw/wv mice lost weight and became osteopenic after 2 × 5 Gy irradiations but these abnormalities were negligible after 5 Gy irradiation. Importantly, adoptive transfer of wild-type cells into Kitw/wv mice restored normal Kit expression in bone marrow. Together, these findings provide strong evidence for efficient engraftment with purified HSCs after lethal TBI with minimal collateral damage to bone. This approach will be useful for investigating mechanisms by which hematopoietic lineage cells regulate bone metabolism.
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| 47. |
- Disney-Hogg, Linden, et al.
(författare)
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Impact of atopy on risk of glioma : a Mendelian randomisation study
- 2018
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: An inverse relationship between allergies with glioma risk has been reported in several but not all epidemiological observational studies. We performed an analysis of genetic variants associated with atopy to assess the relationship with glioma risk using Mendelian randomisation (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.Methods: Two-sample MR was undertaken using genome-wide association study data. We used single nucleotide polymorphisms (SNPs) associated with atopic dermatitis, asthma and hay fever, IgE levels, and self-reported allergy as instrumental variables. We calculated MR estimates for the odds ratio (OR) for each risk factor with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighting (IVW), maximum likelihood estimation (MLE), weighted median estimate (WME) and mode-based estimate (MBE) methods. Violation of MR assumptions due to directional pleiotropy were sought using MR-Egger regression and HEIDI-outlier analysis.Results: Under IVW, MLE, WME and MBE methods, associations between glioma risk with asthma and hay fever, self-reported allergy and IgE levels were non-significant. An inverse relationship between atopic dermatitis and glioma risk was found by IVW (OR 0.96, 95% confidence interval (CI) 0.93-1.00, P = 0.041) and MLE (OR 0.96, 95% CI 0.94-0.99, P = 0.003), but not by WME (OR 0.96, 95% CI 0.91-1.01, P = 0.114) or MBE (OR 0.97, 95% CI 0.92-1.02, P = 0.194).Conclusions: Our investigation does not provide strong evidence for relationship between atopy and the risk of developing glioma, but findings do not preclude a small effect in relation to atopic dermatitis. Our analysis also serves to illustrate the value of using several MR methods to derive robust conclusions.
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| 48. |
- Disney-Hogg, Linden, et al.
(författare)
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Influence of obesity-related risk factors in the aetiology of glioma
- 2018
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 118:7, s. 1020-1027
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity and related factors have been implicated as possible aetiological factors for the development of glioma in epidemiological observation studies. We used genetic markers in a Mendelian randomisation framework to examine whether obesity-related traits influence glioma risk. This methodology reduces bias from confounding and is not affected by reverse causation. METHODS: Genetic instruments were identified for 10 key obesity-related risk factors, and their association with glioma risk was evaluated using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. The estimated odds ratio of glioma associated with each of the genetically defined obesity-related traits was used to infer evidence for a causal relationship. RESULTS: No convincing association with glioma risk was seen for genetic instruments for body mass index, waist-to-hip ratio, lipids, type-2 diabetes, hyperglycaemia or insulin resistance. Similarly, we found no evidence to support a relationship between obesity-related traits with subtypes of glioma-glioblastoma (GBM) or non-GBM tumours. CONCLUSIONS: This study provides no evidence to implicate obesity-related factors as causes of glioma.
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| 49. |
- Ebejer, Jane L., et al.
(författare)
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Genetic and Environmental Influences on Inattention, Hyperactivity-Impulsivity, and Reading: Kindergarten to Grade 2
- 2010
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Ingår i: Scientific Studies of Reading. - : Taylor and Francis. - 1088-8438 .- 1532-799X. ; 14:4, s. 293-316
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Tidskriftsartikel (refereegranskat)abstract
- Twin children from Australia, Scandinavia, and the United States were assessed for inattention, hyperactivity-impulsivity, and reading across the first 3 school years. Univariate behavior-genetic analyses indicated substantial heritability for all three variables in all years. Longitudinal analyses showed one genetic source operating across the time span and a second entering in the second school year for each variable, though possibly not reliable for inattention. Other analyses confirmed previous findings of pleiotropy (shared genes) between inattention and reading and showed that this genetic overlap is in place from kindergarten onwards and is restricted to one of the genetic sources that affect reading and inattention. The results extend previous conclusions about the developmental trajectories of inattention, hyperactivity-impulsivity, and reading and their relationships. Limitations of this study are discussed, as are educational implications.
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| 50. |
- Elwér, Åsa, et al.
(författare)
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A Retrospective Longitudinal Study of Cognitive and Language Skills in Poor Reading Comprehension
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Fifty-six specific poor reading comprehenders (SPRC) were selected in grade 4 and retrospectively compared to good comprehenders at preschool age 5 and at the end of kindergarten, grade 1 and 2. The results showed a widespread language-deficit profile in children with SPRC, including deficits in vocabulary, grammar, verbal memory and early phonological awareness in a large part of the sample beginning in preschool. The reading comprehension deficits in children with SPRC were not as apparent in earlier assessments at grade 1 and 2, likely because of the greater dependence on word decoding in reading comprehension in the early grades.
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