| 1. |
|
|
| 2. |
|
|
| 3. |
- Artigas Soler, María, et al.
(författare)
-
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
-
Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
|
|
| 4. |
- Bousquet, J, et al.
(författare)
-
Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper
- 2012
-
Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 158:3, s. 216-231
-
Tidskriftsartikel (refereegranskat)abstract
- Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
|
|
| 5. |
|
|
| 6. |
- Craddock, Nick, et al.
(författare)
-
Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
-
Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
|
|
| 7. |
- Elks, Cathy E, et al.
(författare)
-
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
-
Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
|
|
| 8. |
|
|
| 9. |
- van der Harst, Pim, et al.
(författare)
-
Seventy-five genetic loci influencing the human red blood cell
- 2012
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
-
Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Zheng, Hou-Feng, et al.
(författare)
-
WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk
- 2012
-
Ingår i: PLoS genetics. - SAN FRANCISCO, USA : PUBLIC LIBRARY SCIENCE. - 1553-7404. ; 8:7, s. e1002745-
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10(-12), and -0.16 SD per G allele, P = 1.2×10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10(-6) and rs2707466: OR = 1.22, P = 7.2×10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10(-13)
|
|
| 15. |
- Darsow, U., et al.
(författare)
-
ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis
- 2010
-
Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 1468-3083 .- 0926-9959. ; 24:3, s. 317-328
-
Forskningsöversikt (refereegranskat)abstract
- Background The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. Methods EADV eczema task force developed its guideline for atopic dermatitis diagnosis and treatment based on literature review and repeated consenting group discussions. Results and Discussion Basic therapy relies on hydrating topical treatment and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin antagonists is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the topical calcineurin inhibitors, tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti-inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial/antiseptic treatment. Systemic antihistamines (H1) can relieve pruritus, but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programmes have been proven to be helpful.
|
|
| 16. |
- Grundberg, Elin, et al.
(författare)
-
Mapping cis- and trans-regulatory effects across multiple tissues in twins.
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
-
Tidskriftsartikel (refereegranskat)abstract
- Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. Using identity-by-descent estimates, we show that at least 40% of the total heritable cis effect on expression cannot be accounted for by common cis variants, a finding that reveals the contribution of low-frequency and rare regulatory variants with respect to both transcriptional regulation and complex trait susceptibility. We show that a substantial proportion of gene expression heritability is trans to the structural gene, and we identify several replicating trans variants that act predominantly in a tissue-restricted manner and may regulate the transcription of many genes.
|
|
| 17. |
- Ka, Sojeong, et al.
(författare)
-
The expression of carnitine palmitoyl-CoA transferase-1B is influenced by a cis-acting eQTL in two chicken lines selected for high and low body weight
- 2013
-
Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 45:9, s. 367-376
-
Tidskriftsartikel (refereegranskat)abstract
- Carnitine palmitoyl-CoA transferase-1B is a mitochondrial enzyme in the fatty acid oxidation pathway. In a previous study, CPT1B was identified as differentially expressed in the hypothalamus of two lines of chickens established by long-term selection for high (HWS) or low (LWS) body weight. Mammals have three paralogs (CPT1a, b and c) while non-mammalian vertebrates only have two (CPT1A, B). CPT1A is expressed in liver and CPT1B in muscle. CPT1c is expressed in hypothalamus, where it regulates feeding and energy expenditure. We identified an intronic length polymorphism, fixed for different alleles in the two populations and mapped the hitherto missing CPT1B locus in the chicken genome assembly, to the distal tip of chromosome 1p. Based on molecular phylogeny and gene synteny we suggest that chicken CPT1B is pro-orthologous of the mammalian CPT1c. Chicken CPT1B was differentially expressed in both muscle and hypothalamus but in opposite directions: higher levels in hypothalamus but lower levels in muscle in the HWS than in the LWS line. Using an advanced inter-cross population of the lines, CPT1B expression was found to be influenced by a cis-acting expression quantitative trait locus in muscle. The increased expression in hypothalamus and reduced expression in muscle is consistent with an increased food intake in the HWS line and at the same time reduced fatty acid oxidation in muscle yielding a net accumulation of energy intake and storage. The altered expression of CPT1B in hypothalamus and peripheral tissue is likely to be a mechanism contributing to the remarkable difference between lines.
|
|
| 18. |
- Keefover-Ring, Ken, et al.
(författare)
-
Phenylpropanoid glycosides of Mimulus guttatus (yellow monkeyflower)
- 2014
-
Ingår i: Phytochemistry Letters. - : Elsevier BV. - 1874-3900 .- 1876-7486. ; 10, s. 132-139
-
Tidskriftsartikel (refereegranskat)abstract
- Yellow monkeyflower [Mimulus guttatus DC., (Phyrmaceae)] has long been a model plant species for studies in genetics, evolution, and ecology, including plant-animal interactions. Nonetheless, exceedingly little is known about its secondary chemistry. We have discovered that the foliage of yellow monkeyflower contains a diverse suite of phenylpropanoid glycosides (PPGs); a class of compounds with many known biological activities. Using H-1 and C-13 NMR and UV and MS chromatography techniques, we positively identified five PPGs from the leaves of yellow monkeyflower. Four of these compounds occur in other species and one is previously undescribed. We also present UV and high- resolution tandem MS data that putatively identify 11 additional foliar compounds as PPGs. This initial discovery and elucidation of yellow monkeyflower's secondary chemistry will be important for continued study of the genetics and ecology of this model species. (C) 2014 Phytochemical Society of Europe.
|
|
| 19. |
- Kemp, John P, et al.
(författare)
-
Does bone resorption stimulate periosteal expansion? A cross sectional analysis of β-C-telopeptides of type I collagen (CTX), genetic markers of the RANKL pathway, and periosteal circumference as measured by pQCT.
- 2014
-
Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 29:4, s. 1015-1024
-
Tidskriftsartikel (refereegranskat)abstract
- We hypothesised that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum β-C-telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodelling such as cortical bone mineral density (BMDC ). CTX and mid-tibial pQCT scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass and height. CTX was positively related to PC [β= 0.19 (0.13, 0.24)] (coefficient=SD change per SD increase in CTX, 95% CI)], but inversely associated with BMDC [β= -0.46 (-0.52,-0.40)] and cortical thickness [β= -0.11 (-0.18, -0.03)]. CTX was positively related to bone strength as reflected by the strength-strain index (SSI) [β= 0.09 (0.03, 0.14)]. To examine the causal nature of this relationship, we then analysed whether SNPs within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding RANK, RANKL and OPG were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (P<0.05 cut-off) (n=2379). Subsequently, we performed a meta-analysis of associations between these SNPs and PC in ALSPAC (n=3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n=938) and the Young Finns Study (YFS) (n=1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (P<0.05 cut-off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion.
|
|
| 20. |
- Limborg, M. T., et al.
(författare)
-
Imprints from genetic drift and mutation imply relative divergence times across marine transition zones in a pan-European small pelagic fish (Sprattus sprattus)
- 2012
-
Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 109:2, s. 96-107
-
Tidskriftsartikel (refereegranskat)abstract
- Geographic distributions of most temperate marine fishes are affected by postglacial recolonisation events, which have left complex genetic imprints on populations of marine species. This study investigated population structure and demographic history of European sprat (Sprattus sprattus L.) by combining inference from both mtDNA and microsatellite genetic markers throughout the species' distribution. We compared effects from genetic drift and mutation for both genetic markers in shaping genetic differentiation across four transition zones. Microsatellite markers revealed significant isolation by distance and a complex population structure across the species' distribution (overall theta(ST) = 0.038, P<0.01). Across transition zones markers indicated larger effects of genetic drift over mutations in the northern distribution of sprat contrasting a stronger relative impact of mutation in the species' southern distribution in the Mediterranean region. These results were interpreted to reflect more recent divergence times between northern populations in accordance with previous findings. This study demonstrates the usefulness of comparing inference from different markers and estimators of divergence for phylogeographic and population genetic studies in species with weak genetic structure, as is the case in many marine species. Heredity (2012) 109, 96-107; doi:10.1038/hdy.2012.18; published online 2 May 2012
|
|
| 21. |
- Mellema, J.J., et al.
(författare)
-
Biomechanical studies: Science (f)or common sense?
- 2014
-
Ingår i: Injury. - : Elsevier. - 0020-1383 .- 1879-0267. ; 45:12, s. 2035-2039
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: It is our impression that many biomechanical studies invest substantial resources studying the obvious: that more and larger metal is stronger. The purpose of this study is to evaluate if a subset of biomechanical studies comparing fixation constructs just document common sense. Methods: Using a web-based survey, 274 orthopaedic surgeons and 81 medical students predicted the results of 11 biomechanical studies comparing fracture fixation constructs (selected based on the authors sense that the answer was obvious prior to performing the study). Sensitivity, specificity, and accuracy were calculated according to standard formulas. The agreement among the observers was calculated by using a multirater kappa, described by Siegel and Castellan. Results: The accuracy of predicting outcomes was 80% or greater for 10 of 11 studies. Accuracy was not influenced by level of experience (i.e., time in practice and medical students vs. surgeons). There were substantial differences in accuracy between observers from different regions. The overall categorical rating of inter-observer reliability according to Landis and Koch was moderate (k = 0.55; standard error (SE) = 0.01). Conclusion: The results of a subset of biomechanical studies comparing fracture fixation constructs can be predicted prior to doing the study. As these studies are time and resource intensive, one criterion for proceeding with a biomechanical study should be that the answer is not simply a matter of common sense. © 2014 Elsevier Ltd. All rights reserved.
|
|
| 22. |
- Neuhaus, V., et al.
(författare)
-
Scapula fractures: Interobserver reliability of classification and treatment
- 2014
-
Ingår i: Journal of Orthopaedic Trauma. - : Lippincott, Williams andamp; Wilkins. - 0890-5339 .- 1531-2291. ; 28:3, s. 124-129
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: There is substantial variation in the classification and management of scapula fractures. The first purpose of this study was to analyze the interobserver reliability of the OTA/AO classification and the New International Classification for Scapula Fractures. The second purpose was to assess the proportion of agreement among orthopaedic surgeons on operative or nonoperative treatment. Design: Web-based reliability study. Setting: Independent orthopaedic surgeons from several countries were invited to classify scapular fractures in an online survey. Participants: One hundred three orthopaedic surgeons evaluated 35 movies of three-dimensional computerized tomography reconstruction of selected scapular fractures, representing a full spectrum of fracture patterns. Main Outcome Measurements: Fleiss kappa (κ) was used to assess the reliability of agreement between the surgeons. Results: The overall agreement on the OTA/AO classification was moderate for the types (A, B, and C, κ = 0.54) with a 71% proportion of rater agreement (PA) and for the 9 groups (A1 to C3, κ = 0.47) with a 57% PA. For the New International Classification, the agreement about the intraarticular extension of the fracture (Fossa (F), κ = 0.79) was substantial and the agreement about a fractured body (Body (B), κ = 0.57) or process was moderate (Process (P), κ = 0.53); however, PAs were more than 81%. The agreement on the treatment recommendation was moderate (κ = 0.57) with a 73% PA. Conclusions: The New International Classification was more reliable. Body and process fractures generated more disagreement than intraarticular fractures and need further clear definitions. Copyright © 2013 by Lippincott Williams and Wilkins.
|
|
| 23. |
- Olivier, Jocelien D A, et al.
(författare)
-
The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring
- 2013
-
Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 7, s. 73-
-
Forskningsöversikt (refereegranskat)abstract
- It has been estimated that 20% of pregnant women suffer from depression and it is well-documented that maternal depression can have long-lasting effects on the child. Currently, common treatment for maternal depression has been the selective serotonin reuptake inhibitor medications (SSRIs) which are used by 2-3% of pregnant women in the Nordic countries and by up to 10% of pregnant women in the United States. Antidepressants cross the placenta and are transferred to the fetus, thus, the question arises as to whether children of women taking antidepressants are at risk for altered neurodevelopmental outcomes and, if so, whether the risks are due to SSRI medication exposure or to the underlying maternal depression. This review considers the effects of maternal depression and SSRI exposure on offspring development in both clinical and preclinical populations. As it is impossible in humans to study the effects of SSRIs without taking into account the possible underlying effects of maternal depression (healthy pregnant women do not take SSRIs), animal models are of great value. For example, rodents can be used to determine the effects of maternal depression and/or perinatal SSRI exposure on offspring outcomes. Unraveling the joint (or separate) effects of maternal depression and SSRI exposure will provide more insights into the risks or benefits of SSRI exposure during gestation and will help women make informed decisions about using SSRIs during pregnancy.
|
|
| 24. |
- Pratt, Jessica D., et al.
(författare)
-
Genetically based latitudinal variation in Artemisia californica secondary chemistry
- 2014
-
Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 123:8, s. 953-963
-
Tidskriftsartikel (refereegranskat)abstract
- Steep climatic gradients may select for clinal adaptation in plant functional traits with implications for interspecific interactions and response to future climate change. Terpenes are common in Mediterranean environments and mediate plant interactions with both the abiotic and biotic environment, including herbivores. Clines in traits such as terpenes have received much attention because they are linked to plant fitness and experience strong selection from the abiotic and biotic environment. In this study, we tested for intraspecific variation in Artemisia californica terpene chemistry in a common garden of plants sourced from populations spanning a large precipitation gradient (6 latitude) and grown in treatments of high and low precipitation. We found genetic variation in terpene richness, diversity, concentration and composition among A. californica populations spanning this species' range. Of these traits, terpene composition and monoterpene concentration varied clinally with respect to source site latitude. Regarding terpene composition, pairwise dissimilarity among populations increased in parallel with geographic distance between source sites. At the same time, monoterpene concentration decreased monotonically from plants of southern origin (source sites with high temperature, aridity, and precipitation variability) to plants of northern origin. Our precipitation manipulation suggests that phenotypic selection by precipitation may underlie this clinal variation in monoterpene concentration, and that monoterpene concentration and other aspects of terpene chemistry are not phenotypically plastic. In summary, this study provides novel evidence for a genetically based latitudinal cline in plant secondary chemistry and suggests that adaptation to a key aspect of the abiotic environment may contribute to this intraspecific variation. Accordingly, changes in terpene chemistry under projected future climates will likely occur solely through the relatively slow process of adaptation, with important consequences for plant interactions with the abiotic environment and a diverse community of associates.
|
|
| 25. |
- Stalder, J-F, et al.
(författare)
-
Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe.
- 2011
-
Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 66, s. 1114-1121
-
Tidskriftsartikel (refereegranskat)abstract
- To cite this article: Stalder J-F, Barbarot S, Wollenberg A, Holm EA, De Raeve L, Seidenari S, Oranje A, Deleuran M, Cambazard F, Svensson A, Simon D, Benfeldt E, Reunala T, Mazereeuv J, Boralevi F, Kunz B, Misery L, Mortz CG, Darsow U, Gelmetti C, Diepgen T, Ring J, Moehrenschlager M, Gieler U, Taïeb A, for the PO-SCORAD Investigators Group. Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02577.x. ABSTRACT: Background: Patient-oriented medicine is an emerging concept, encouraged by the World Health Organization, to greater involvement of the patient in the management of chronic diseases. The Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index is a self-assessment score allowing the patient to comprehensively evaluate the actual course of atopic dermatitis (AD), using subjective and objective criteria derived mainly from the SCORAD, a validated AD severity clinical assessment tool. Objectives: To validate the PO-SCORAD index in a large European population of patients exhibiting all forms of AD severity by assessing its correlation with the SCORAD index. Patients/methods: Four hundred and seventy-one patients (185 adults, 286 children) consulting for AD in hospitals from 9 European countries were recruited. The investigators and the patients used the SCORAD and PO-SCORAD scales, respectively, to assess AD severity at inclusion (D0) and 28 ± 7 days later (D28). Results: Patient-Oriented SCORing Atopic Dermatitis and SCORAD scores were significantly correlated at D0 [r = 0.67 (95% CI: 0.62; 0.72), P < 0.0001]. Consistency was confirmed at D28, with a stronger linear correlation between both scales [r = 0.79 (95% CI: 0.75; 0.83), P < 0.0001]. Absolute changes from baseline in SCORAD and PO-SCORAD scores were also significantly correlated [r= 0.71 (95% CI: 0.64; 0.76), P < 0.0001]. Although no specific intervention was investigated, AD improved over the study, with a decrease of PO-SCORAD and SCORAD scores from D0 to D28 by -19.19% and -24.39%, respectively. The consistency of the correlations was similar in the adult and children groups. Conclusions: This study validated the use of PO-SCORAD to self-assess AD severity and demonstrated its good correlation with SCORAD.
|
|
| 26. |
- Taal, H. Rob, et al.
(författare)
-
Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
-
Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
|
|
| 27. |
- Tyrrell, Jessica, et al.
(författare)
-
Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight.
- 2012
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 21:24, s. 5344-5358
-
Tidskriftsartikel (refereegranskat)abstract
- Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P = 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: -4to 14 g; P = 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.
|
|
