| 1. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 2. |
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| 3. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 4. |
- Kirchhoff, Tomas, et al.
(författare)
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Breast cancer risk and 6q22.33 : combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2
- 2012
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Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
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| 5. |
- 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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| 6. |
- Garpvall, K., et al.
(författare)
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Admission screening and cohort care decrease carbapenem resistant enterobacteriaceae in Vietnamese pediatric ICUs
- 2021
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Ingår i: Antimicrobial Resistance and Infection Control. - : BMC. - 2047-2994. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess if admission screening for Carbapenem Resistant Enterobacteriaceae (CRE) and cohort care can reduce CRE acquisition (CRE colonization during hospital stay), Hospital Acquired Infections (HAI), hospital-stay, mortality, and costs in three Intensive Care Units (ICUs) at the Vietnamese National Childrens Hospital. Method CRE screening using rectal swabs and ChromIDCarbas elective culture at admission and if CRE negative, once weekly. Patients were treated in cohorts based on CRE colonization status. Results CRE colonization at baseline point-prevalence screening was 76.9% (103/134). Of 941 CRE screened at admission, 337 (35.8%) were CREpos. 694 patients met inclusion criteria. The 244 patients CRE negative at admission and screened > 2 times were stratified in 8 similar size groups (periods), based on time of admission. CRE acquisition decreased significant (OR - 3.2, p < 0.005) from 90% in period 2 (highest) to 48% in period 8 (last period). Patients with CRE acquisition compared to no CRE acquisition had a significantly higher rate of culture confirmed HAI, n = 20 (14%) vs. n = 2 (2%), longer hospital stays, 3.26 vs. 2.37 weeks, and higher total treatment costs, 2852 vs. 2295 USD. Conclusion Admission CRE screening and cohort care in pediatric ICUs significantly decreased CRE acquisition, cases of HAI and duration of hospital-stay.
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| 7. |
- Gorishnyy, T.Z., et al.
(författare)
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Optimization of wear-resistant coating architectures using finite element analysis
- 2003
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Ingår i: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films. - : American Vacuum Society. - 0734-2101 .- 1520-8559. ; 21:1, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- The design of successful wear-resistant coating architectures requires simultaneous consideration of several factors. In particular, coatings which consist of CrN layers of varying thickness separated by thin Cr layers have the highest wear resistance for both aluminum and steel substrate materials, but a methodology was needed to optimize both the overall coating design and the individual layer thicknesses. This paper provides an initial step toward the development of future application specific coating designs and improved coating design methodologies.
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| 8. |
- Grasby, Katrina L., et al.
(författare)
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Estimating Classroom-Level Influences on Literacy and Numeracy: A Twin Study
- 2020
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Ingår i: Journal of Educational Psychology. - : AMER PSYCHOLOGICAL ASSOC. - 0022-0663 .- 1939-2176. ; 112:6, s. 1154-1166
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Tidskriftsartikel (refereegranskat)abstract
- Classroom-level influences on literacy skills in kindergarten through Grade 2, and on literacy and numeracy skills in Grades 3. 5, 7, and 9. were examined by comparing the similarity of twins who shared or did not share classrooms with each other. We analyzed two samples using structural equation modeling adapted for twin data. The first, Study 1, was of Australia-wide tests of literacy and numeracy, with 1,098; 1,080; 790, and 812 complete twin pairs contributing data for Grades 3, 5, 7, and 9, respectively. The second, Study 2, was of literacy tests from 753 twin pairs from kindergarten through Grade 2, which included a sample of United States and Australian students and was a reanalysis and extension of Byrne et al. (2010). Classroom effects were mostly nonsignificant; they accounted for only 2-3% of variance in achievement when averaged over tests and grades. Although the averaged effects may represent a lower-bound figure for classroom effects, and the design cannot detect classroom influences limited to individual students, the results are at odds with claims in public discourse of substantial classroom-level influences, which are mostly portrayed as teacher effects.
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| 9. |
- Nordlind, Klas, et al.
(författare)
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Effect of chronic mild stress on skin and brain in the NC/Nga atopic-like mouse
- 2011
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Ingår i: JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol 131 Issue S2 (September 2011). - : Nature Publishing Group. ; , s. S116-S116
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Konferensbidrag (refereegranskat)abstract
- Atopic eczema is often worsened by stress. We have studied the effect of chronic mild stress in the atopic-like NC/Nga mouse strain. The mice were subjected to chronic mild stress for 12 weeks and eczema was induced by applying a mite antigen (Dermatophagoides pteronyssinus) on the ears for the last 4 weeks. The mice were divided into stressed eczematous, non-stressed eczematousand stressed control groups. Serum corticosterone levels were determined at the endpoint of the experiment. The biopsies from skin and brain have been analyzed using immunohistochemistry and RT-PCR. The diameter of the ears was larger in the stressed eczematous group compared to the other groups. Moreover, the corticosterone levels were significantly lower in the stressedeczematous group. The neuromediators being studied are serotonin, its transporter protein, as well as its receptors, and the tachykinin substance P and its receptor neurokinin-1.
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| 10. |
- Ran, C., et al.
(författare)
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Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. (C) 2016 The Author(s). Published by Elsevier Inc.
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