| 1. |
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| 2. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 3. |
- Haghighi, Mona, et al.
(författare)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 4. |
- Johnson, Randi K., et al.
(författare)
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Metabolite-related dietary patterns and the development of islet autoimmunity
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts. © 2019, The Author(s).
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| 5. |
- Krischer, Jeffrey P, et al.
(författare)
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Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 42:6, s. 1051-1060
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.
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| 6. |
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| 7. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 8. |
- Mavaddat, Nasim, et al.
(författare)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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| 9. |
- Rewers, Marian, et al.
(författare)
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The Environmental Determinants of Diabetes in the Young (TEDDY) Study
- 2008
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1150, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The etiology of type 1 diabetes (T1D) remains unknown, but a growing body of evidence points to infectious agents and/or components of early childhood diet. The National Institutes of Health has established the TEDDY Study consortium of six clinical centers in the United States and Europe and a data coordinating center to identify environmental factors predisposing to, or protective against, islet autoimmunity and T1D. From 2004-2009, TEDDY will screen more than 360,000 newborns from both the general population and families already affected by T1D to identify an estimated 17,804 children with high-risk HLA-DR,DQ genotypes. Of those, 7,801 (788 first-degree relatives and 7,013 newborns with no family history of T1D) will be enrolled in prospective follow-up beginning before the age of 4.5 months. As of May 2008, TEDDY has screened more than 250,000 newborns and enrolled nearly 5,000 infants--approximately 70% of the final cohort. Participants are seen every 3 months up to 4 years of age, with subsequent visits every 6 months until the subject is 15 years of age. Blood samples are collected at each visit for detection of candidate infectious agents and nutritional biomarkers; monthly stool samples are collected for infectious agents. These samples are saved in a central repository. Primary endpoints include (1) appearance of one or more islet autoantibodies (to insulin, GAD65 or IA-2) confirmed at two consecutive visits; (2) development of T1D. By age 15, an estimated 800 children will develop islet autoimmunity and 400 will progress to T1D; 67 and 27 children have already reached these endpoints.
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| 10. |
- Rydin, Catarina, et al.
(författare)
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Deep divergences in the coffee family and the systematic position of Acranthera
- 2009
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Ingår i: Plant Systematics and Evolution. - : Springer Science and Business Media LLC. - 0378-2697 .- 1615-6110. ; 278, s. 101-123
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Tidskriftsartikel (refereegranskat)abstract
- Despite extensive efforts, there are unresolved questions on evolutionary relationships in the angiosperm family Rubiaceae. Here, information from six loci and 149 Rubiaceae taxa provide new insights. Acranthera and Coptosapelta are strongly supported as sisters. Pollen grains of Acranthera possess several features common in Rubiaceae, but amongst potential similarities with the unusual grains of Coptosapelta are the nature of the apertures andthe structure of the sexine. Luculia, Acranthera and Coptosapelta are excluded from the three subfamilies Ixoroideae, Cinchonoideae and Rubioideae. Sipaneeae and Condamineeae form a clade, sister to remaining Ixoroideae. Rondeletieae and Guettardeae are sisters to remaining Cinchonoideae. Colletoecema is sister to remaining Rubioideae, followed by the Urophylleae–Ophiorrhizeae clade. Nuclear ITS provided structured information at all phylogenetic levels, but the main gain from adding nrITS was the increased resolution. Average support values also increased but were generally high also without nrITS andthe increase was not statistically significant.
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| 11. |
- Smedmark, Jenny E. E., et al.
(författare)
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A Phylogeny of Urophylleae (Rubiaceae) based on rps16 intron data
- 2008
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Ingår i: Taxon. - 0040-0262. ; 57:1, s. 24-32
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Tidskriftsartikel (refereegranskat)abstract
- This is the first study of phylogenetic relationships within the pantropical group Urophylleae. Previous studies have included few representatives from this group and little is known about its phylogeny. Here we use sequence data from the rps16 intron to address the question of where the four genera Temnopteryx, Pentaloncha, Pleiocarpidia, and Poecilocalyx, which have sometimes been classified in this group belong. By using different outgroups we show that there is conflict regarding the resolution among lineages in Rubioideae, which partly affects the support for relationships within Urophylleae. Urophylleae is shown to consist of two sister groups, one larger consisting only of Old World taxa and one smaller including the New World genera Amphidasya and Raritebe, and as sister of these two groups the African monotypic genus Temnopteryx. Pentaloncha, Pleiocarpidia, and Poecilocalyx all belong in the large Old World clade, which only comprises taxa included in the original circumscription of Urophylleae. Relationships within this group are not completely resolved, but Poecilocalyx is found to be the sister of Stelechantha and Pleiocarpidia to be the sister of Urophyllum leucophleum. Urophyllum is paraphyletic, as it seems to include Maschalocorymbus, Pleiocarpidia, Praravinia, and Pravinaria. It is not clear from the present analysis whether Pauridiantha is monophyletic or not.
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| 12. |
- Smedmark, Jenny E. E., et al.
(författare)
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Divergence time uncertainty and historical biogeography reconstruction - an example from Urophylleae (Rubiaceae)
- 2010
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 37:12, s. 2260-2274
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Tidskriftsartikel (refereegranskat)abstract
- Aim When hypotheses of historical biogeography are evaluated, age estimates of individual nodes in a phylogeny often have a direct impact on what explanation is concluded to be most likely. Confidence intervals of estimated divergence times obtained in molecular dating analyses are usually very large, but the uncertainty is rarely incorporated in biogeographical analyses. The aim of this study is to use the group Urophylleae, which has a disjunct pantropical distribution, to explore how the uncertainty in estimated divergence times affects conclusions in biogeographical analysis. Two hypotheses are evaluated: (1) long-distance dispersal from Africa to Asia and the Neotropics, and (2) a continuous distribution in the boreotropics, probably involving migration across the North Atlantic Land Bridge, followed by isolation in equatorial refugia. Location Tropical and subtropical Asia, tropical Africa, and central and southern tropical America. Methods This study uses parsimony and Bayesian phylogenetic analyses of chloroplast DNA and nuclear ribosomal DNA data from 56 ingroup species, beast molecular dating and a Bayesian approach to dispersal-vicariance analysis (Bayes-DIVA) to reconstruct the ancestral area of the group, and the dispersal-extinction-cladogenesis method to test biogeographical hypotheses. Results When the two models of geographic range evolution were compared using the maximum likelihood (ML) tree with mean estimates of divergence times, boreotropical migration was indicated to be much more likely than long-distance dispersal. Analyses of a large sample of dated phylogenies did, however, show that this result was not consistent. The age estimate of one specific node had a major impact on likelihood values and on which model performed best. The results show that boreotropical migration provides a slightly better explanation of the geographical distribution patterns of extant Urophylleae than long-distance dispersal. Main conclusions This study shows that results from biogeographical analyses based on single phylogenetic trees, such as a ML or consensus tree, can be misleading, and that it may be very important to take the uncertainty in age estimates into account. Methods that account for the uncertainty in topology, branch lengths and estimated divergence times are not commonly used in biogeographical inference today but should definitely be preferred in order to avoid unwarranted conclusions.
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| 13. |
- Smedmark, Jenny E. E., et al.
(författare)
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Inferring geographic range evolution of a pantropical tribe in the coffee family (Lasiantheae, Rubiaceae) in the face of topological uncertainty
- 2014
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Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903 .- 1095-9513. ; 70, s. 182-194
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Tidskriftsartikel (refereegranskat)abstract
- In this study we explore what historical biogeographic events are responsible for the wide and disjunct distribution of extant species in Lasiantheae, a pantropical group of trees and shrubs in the coffee family. Three of the genera in the group, Lasianthus, Saldinia, and Trichostachys, are found to be monophyletic, while there are indications that the fourth, Ronabea, is paraphyletic. We also address how the uncertainty in topology and divergence times affects the level of confidence in the biogeographic reconstruction. A data set consisting of chloroplast and nuclear ribosomal DNA data was analyzed using a Bayesian relaxed molecular clock approach to estimate phylogenetic relationships and divergence times, and the dispersal-extinction-cladogenesis (DEC) method to reconstruct geographic range evolution. Our results show that the Lasiantheae stem lineage originated in the neotropics, and the group expanded its range to the palaeotropics during the Eocene, either by continental migration through the boreotropics or by transatlantic long-distance dispersal. Two cases of Oligocene/Miocene over water-dispersal were also inferred, once from the paleotropics to the neotropics within Lasianthus, and once to Madagascar, concurrent with the origin of Saldinia. A lot of the diversification within Lasianthus took place during the Miocene and may have been influenced by climatic factors such as a period of markedly warm and moist climate in Asia and the aridification of the interior of the African continent. When biogeographic reconstructions were averaged over a random sample of 1000 dated phylogenies, the confidence in the biogeographic reconstruction decreased for most nodes, compared to when a single topology was used. A good understanding of phylogenetic relationships is necessary to understand the biogeographic history of a group, bit since the phylogeny is rarely completely known it is important to include phylogenetic uncertainty in biogeographic analysis. For nodes where the resolution is uncertain, the use of a single best topology as a basis for biogeographic analysis will result in inflated confidence in a biogeographic reconstruction which may be just one of several possible reconstructions.
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| 14. |
- Smedmark, Jenny E. E., et al.
(författare)
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Molecular systematics and incongruent gene trees of Urophylleae (Rubiaceae)
- 2011
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Ingår i: Taxon. - 0040-0262 .- 1996-8175. ; 60:5, s. 1397-1406
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Tidskriftsartikel (refereegranskat)abstract
- The phylogeny of the Pantropical tribe Urophylleae is poorly understood. Earlier phylogenetic work has identified major evolutionary lineages within the group, each geographically restricted to a single continent, but relationships among taxa within these lineages are so far largely unresolved. This study uses parsimony and Bayesian phylogenetic analyses of chloroplast DNA (cpDNA) and nuclear ribosomal DNA (nrDNA) to resolve phylogenetic relationships within Urophylleae. The results show that there are conflicts between cpDNA and nrDNA regarding species-level relationships within Pauridiantha, Urophyllum, and Amphidasya, which provides evidence of a complex genetic history. Different types of tests are used to explore the magnitude of the incongruence and locate the exact nodes in the two gene trees that are in conflict. This approach makes it possible to use the topology from the combined analysis, despite the separate datasets being strongly incongruent, since areas of the tree that are free from conflict can be identified. Based on the results presented in this study, Urophylleae is indicated to consist of Temnopteryx, Raritebe, Amphidasya, Urophyllum s.l., Pauridiantha s.l., and Pentaloncha. Several genera are shown to be nested inside Pauridiantha, two of which have already been included in Pauridiantha based on other data (Pamplethantha, Commitheca), and two which are included in this genus here (Poecilocalyx, Stelechantha). Likewise, three genera are shown to be ingroups in Urophyllum (Pravinaria, Maschalocorymbus, Pleiocarpidia), and are therefore subsumed under this genus. New combinations under Pauridiantha are proposed for three species in Poecilocalyx and three species in Stelechantha, as well as new combinations under Urophyllum for two species in Pravinaria and 17 species in Pleiocarpidia. For one of the latter species a new name is presented to avoid homonymy.
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| 15. |
- Smedmark, Jenny E. E., 1972-
(författare)
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The evolutionary history of Geum (Rosaceae, Colurieae) : a study of ancient allopolyploid speciation
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Allopolyploid speciation plays an important role in flowering plant evolution. Its contribution to diversity has been suggested to be significant in Geum. In this thesis the evolutionary history of Geum and its closest relatives was investigated by phylogenetic analysis of sequence data from the trnL-trnF region of the chloroplast, the ITS region of nuclear ribosomal DNA, and the nuclear low-copy gene GBSSI. The data were analysed using parsimony, Bayesian inference, and maximum likelihood. The phylogenies were used to test hypotheses about allopolyploid speciation, to investigate the evolution of some fruit characters and the implications for the taxonomy of the group. The GBSSI phylogenies indicated that allopolyploid speciation has occurred in the history of Geum. However, earlier hypotheses based on cytogenetic data about the allopolyploid ancestry of certain species were rejected. One tetraploid species and a morphologically diverse group of hexaploids, likely also including species with higher ploidy levels, were suggested to be of allopolyploid origin. A hypothesis of reticulate organismal relationships, including two instances where new lineages have been formed by allopolyploidy, was proposed based on the gene trees. A molecular dating analysis indicated that these reticulations occurred several million years ago. None of the previously suggested circumscriptions of Geum, Acomastylis, or Sieversia sensu lato were found to be monophyletic. Nested within Geum sensu lato were Waldsteinia, Coluria, and Taihangia and therefore Geum was recircumscribed to include these taxa. Colurieae, the former Dryadeae (in part), was recircumscribed and given a phylogenetic definition. According to this classification, Colurieae includes Fallugia, Sieversia sensu stricto, and Geum. Morphological evolution within the putative allopolyploid group appears to be homoplasious. Initial optimisation of the presence of a "joint", an abscission layer where the style, or part of it, is shed at maturity, on the gene trees indicated that it evolved four times from persistent, elongating styles. However, scanning electron microscopy showed that the development of the various types of fruits with jointed styles is similar, indicating that the joint and the deciduous segment of the style, of different lineages are homologous. The joint was thus hypothesised to have originated in the ancestral lineage of Waldsteinia and Coluria and to have been passed on via hybridisation to the polyploids. It is, however, only expressed in some lineages among the polyploids.
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| 16. |
- Smith, Laura B., et al.
(författare)
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Psychological manifestations of celiac disease autoimmunity in young children
- 2017
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 139:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Psychological symptoms can be associated with celiac disease; abstract however, this association has not been studied prospectively in a pediatric cohort. We examined mother report of psychological functioning in children persistently positive for tissue transglutaminase autoantibodies (tTGA), defined as celiac disease autoimmunity (CDA), compared with children without CDA in a screening population of genetically at-risk children. We also investigated differences in psychological symptoms based on mothers' awareness of their child's CDA status. METHODS: The Environmental Determinants of Diabetes in the Young study followed 8676 children to identify triggers of type 1 diabetes and celiac disease. Children were tested for tTGA beginning at 2 years of age. The Achenbach Child Behavior Checklist assessed child psychological functioning at 3.5 and 4.5 years of age. RESULTS: At 3.5 years, 66 mothers unaware their child had CDA reported more child anxiety and depression, aggressive behavior, and sleep problems than 3651 mothers of children without CDA (all Ps ≤ .03). Unaware-CDA mothers also reported more child anxiety and depression, withdrawn behavior, aggressive behavior, and sleep problems than 440 mothers aware of their child's CDA status (all Ps ≤.04). At 4.5 years, there were no differences. CONCLUSIONS: In 3.5-year-old children, CDA is associated with increased reports of child depression and anxiety, aggressive behavior, and sleep problems when mothers are unaware of their child's CDA status. Mothers' knowledge of their child's CDA status is associated with fewer reports of psychological symptoms, suggesting that awareness of the child's tTGA test results affects reporting of symptoms.
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| 17. |
- Törn, Carina, et al.
(författare)
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Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
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| 18. |
- Wikström, Niklas, et al.
(författare)
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A Revised Time Tree of the Asterids : Establishing a Temporal Framework For Evolutionary Studies of the Coffee Family (Rubiaceae)
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Divergence time analyses in the coffee family (Rubiaceae) have all relied on the same Gentianales crown group age estimate, reported by an earlier analysis of the asterids, for defining the upper age bound of the root node in their analyses. However, not only did the asterid analysis suffer from several analytical shortcomings, but the estimate itself has been used in highly inconsistent ways in these Rubiaceae analyses. Based on the original data, we here reanalyze the divergence times of the asterids using relaxed-clock models and 14 fossil-based minimum age constraints. We also expand the data set to include an additional 67 taxa from Rubiaceae sampled across all three subfamilies recognized in the family. Three analyses are conducted: a separate analysis of the asterids, which completely mirrors the original asterid analysis in terms of taxon sample and data; a separate analysis of the Gentianales, where the result from the first analysis is used for defining a secondary root calibration point; and a combined analysis where all taxa are analyzed simultaneously. Results are presented in the form of a time-calibrated phylogeny, and age estimates for asterid groups, Gentianales, and major groups of Rubiaceae are compared and discussed in relation to previously published estimates. Our updated age estimates for major groups of Rubiaceae provide a significant step forward towards the long term goal of establishing a robust temporal framework for the divergence of this biologically diverse and fascinating group of plants.
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