| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 5. |
- Gaudet, Mia M., et al.
(författare)
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Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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| 6. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 7. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 8. |
- Lim, Elaine T, et al.
(författare)
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Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10-8) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10-117). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10-4), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers.
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| 9. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 10. |
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| 11. |
- Adu, Cynthia, et al.
(författare)
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Properties of cellulose nanofibre networks prepared from never-dried and dried paper mill sludge
- 2018
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Ingår i: Journal of Cleaner Production. - : Elsevier. - 0959-6526 .- 1879-1786. ; 197:1, s. 765-771
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Tidskriftsartikel (refereegranskat)abstract
- Paper mills yield large volumes of sludge materials which pose an environmental and economic challenge for disposal, despite the fact that they could be a valuable source for cellulose nanofibres (CNF) production. The aim of the study was to evaluate the production process and properties of CNF prepared by mechanical fibrillation of never-dried and dried paper mill sludge (PMS). Atomic force microscopy (AFM) showed that average diameters for both never-dried and dried paper sludge nanofibres (PSNF) were less than 50 nm. The never-dried and dried sludge nanofibres showed no statistical significant difference (p > 0.05) in strength 92 MPa, and 85 MPa and modulus 11 GPa and 10 GPa. The study concludes that paper mill sludge can be used in a dried state for CNF production to reduce transportation and storage challenges posed on industrial scale.
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| 12. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 13. |
- Bussu, Giorgia, et al.
(författare)
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The latent structure of emerging cognitive abilities : An infant twin study
- 2023
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Ingår i: Intelligence. - : Elsevier. - 0160-2896 .- 1873-7935. ; 99, s. 101771-101771
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that genetic factors account for up to 70% of variability in cognition from childhood to adulthood. However, less is known about the first year of life. This study investigated the etiological factors influencing individual variability in different domains of emerging cognitive and motor abilities in early infancy, and to what extent genetic and environmental influences are unique or shared across different domains. We compared multivariate twin models built on scores from the five scales of the Mullen Scales of Early Learning (MSEL) in a community sample of monozygotic and dizygotic twins at 5 months of age (n=567). The results indicated a hierarchical etiological structure whereby a general genetic latent factor accounted for 54% of variance underlying the different domains of emerging cognitive and motor abilities (A=0.54, confidence interval CI=[0; 0.82]). We also found additional genetic influences that were specific to early motor and language development. Unlike previous findings on older children, we did not find significant influences of shared environment on the shared factor (C=0, CI=[0, 0.57]), or any specific scale. Furthermore, influences of unique environment, which include measurement error, were moderate and statistically significant (E=0.46, CI=0.18; 0.81]). This study provides strong evidence for a unitary hierarchical structure across different domains of emerging cognition. Evidence that a single common etiological factor, which we term infant g, contributes to a range of different abilities supports the view that in young infants, intrinsic and general neurodevelopmental processes are key drivers of observable behavioural differences in specific domains.
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| 14. |
- Couch, Fergus J., et al.
(författare)
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AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A consortium of investigators of modifiers of BRCA1/2 study
- 2007
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:7, s. 1416-1421
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Tidskriftsartikel (refereegranskat)abstract
- The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 311 allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.061. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% Cl, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.
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| 15. |
- Divakar, Pradeep K., et al.
(författare)
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Evolution of complex symbiotic relationships in a morphologically derived family of lichen-forming fungi
- 2015
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 208:4, s. 1217-1226
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Tidskriftsartikel (refereegranskat)abstract
- We studied the evolutionary history of the Parmeliaceae (Lecanoromycetes, Ascomycota), one of the largest families of lichen-forming fungi with complex and variable morphologies, also including several lichenicolous fungi. We assembled a six-locus data set including nuclear, mitochondrial and low-copy protein-coding genes from 293 operational taxonomic units (OTUs). The lichenicolous lifestyle originated independently three times in lichenized ancestors within Parmeliaceae, and a new generic name is introduced for one of these fungi. In all cases, the independent origins occurred c. 24 million yr ago. Further, we show that the Paleocene, Eocene and Oligocene were key periods when diversification of major lineages within Parmeliaceae occurred, with subsequent radiations occurring primarily during the Oligocene and Miocene. Our phylogenetic hypothesis supports the independent origin of lichenicolous fungi associated with climatic shifts at the Oligocene-Miocene boundary. Moreover, diversification bursts at different times may be crucial factors driving the diversification of Parmeliaceae. Additionally, our study provides novel insight into evolutionary relationships in this large and diverse family of lichen-forming ascomycetes.
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| 16. |
- 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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| 17. |
- Gonçalo, Margarida, et al.
(författare)
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Allergic contact dermatitis caused by nail acrylates in Europe. An EECDRG study
- 2018
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873. ; 78:4, s. 254-260
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic contact dermatitis (ACD) caused by nail acrylates, also including methacrylates and cyanoacrylates here, is being increasingly reported. Methods: A retrospective study in 11 European Environmental Contact Dermatitis Research Group (EECDRG) clinics collected information on cases of ACD caused by nail acrylates diagnosed by aimed testing between 2013 and 2015. Results: Among 18 228 studied patients, 136 had ACD caused by nail acrylates (0.75%; 95%CI: 0.60–0.90), representing 67.3% (95%CI: 60.4–73.7) of ACD cases caused by acrylates. There were 135 females and 1 male, with a mean age ± standard deviation of 36.7 ± 12.2 years; 59 (43.4%) were exposed as consumers, and 77 (56.6%) were occupationally exposed. Occupational cases were more frequent in southern Europe (83.7%), and were younger (mean age of 33.4 ± 8.9 years); most developed ACD during the first year at work (65.0%), and at least 11.7% had to leave their jobs. Skin lesions involved the hands in 121 patients (88.9%) and the face in 50 (36.8%), with the face being the only affected site in 14 (10.3%). Most patients reacted to two or more acrylates on patch testing, mainly to 2-hydroxyethyl methacrylate (HEMA) (92.5%), 2-hydroxypropyl methacrylate (88.6%), ethylene glycol dimethacrylate (69.2%), and ethyl cyanoacrylate (9.9%). Conclusions: Nail cosmetics were responsible for the majority of ACD cases caused by acrylates, affecting nail beauticians and consumers, and therefore calling for stricter regulation and preventive measures. As HEMA detects most cases, and isolated facial lesions may be overlooked, inclusion of this allergen in the baseline series may be warranted.
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| 18. |
- Johansen, Jeanne D., et al.
(författare)
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European Society of Contact Dermatitis guideline for diagnostic patch testing : recommendations on best practice
- 2015
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 73:4, s. 195-221
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Forskningsöversikt (refereegranskat)abstract
- The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
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| 19. |
- Karmin, Monika, et al.
(författare)
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A recent bottleneck of Y chromosome diversity coincides with a global change in culture.
- 2015
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 25:4
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Tidskriftsartikel (refereegranskat)abstract
- It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
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| 20. |
- Kask, Kristiina, et al.
(författare)
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Patients with premenstrual dysphoric disorder have increased startle response across both cycle phases and lower levels of prepulse inhibition during the late luteal phase of the menstrual cycle
- 2008
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Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X .- 1740-634X. ; 33:9, s. 2283-2290
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with premenstrual dysphoric disorder (PMDD) experience their most intense symptoms during the late luteal phase. The aim of the current study was to compare acoustic startle response and prepulse inhibition in PMDD patients and controls during the follicular and late luteal phases of the menstrual cycle. Following two months of prospective daily ratings on the Cyclicity Diagnoser scale, 30 PMDD patients and 30 asymptomatic controls, between the ages of 20 and 46, were included in the study. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of m. orbicularis oculi. Twenty pulse-alone trials (115 dB 40 ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115 dB 40 ms noise burst preceded at a 100 ms interval by 20 ms prepulses that were 72, 74, 78, or 86 dB. PMDD patients had a significantly higher startle response than controls during both phases of the menstrual cycle (p<0.05). PMDD patients exhibited lower levels of prepulse inhibition with 78 dB and 86 dB prepulses compared to control subjects in the luteal (p<0.01) but not in the follicular phase. Whereas control subjects displayed increased PPI during the late luteal phase compared to the follicular phase (p<0.01), PPI magnitude remained unchanged in PMDD patients between cycle phases. Relative to controls, PMDD patients displayed increased startle reactivity across both menstrual cycle phases and deficits in prepulse inhibition of acoustic startle during the late luteal phase. These findings are consistent with an altered response to ovarian steroids among PMDD patients.
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| 21. |
- Källbom, Susanna, et al.
(författare)
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Effects of water soaking-drying cycles on thermally modified spruce wood-plastic composites
- 2020
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Ingår i: Wood and Fiber Science. - : SOC WOOD SCI TECHNOL. - 0735-6161. ; 52:1, s. 2-12
-
Tidskriftsartikel (refereegranskat)abstract
- The overall aim of this work was to gain more insight on the potential of modified wood (TMW) components for use in wood-thermoplastic composites (WPCs). Laboratory-scale TMWPCs were produced, and the effects of severe water soaking-drying cycles on the samples were studied. Water sorption behavior and resulting dimensional and micromorphological changes were also studied, and the results were compared with those of unmodified wood-plastic composites (UWPCs) used as control. The TMW was prepared by cutting a spruce board into half and subjecting one-half to an atmosphere of superheated steam at atmospheric pressure with a peak temperature of 210 degrees C, with the other unmodified wood (UW) half as a control. The TMW and UW components were then prepared by a Wiley mill and thereafter sifted into smaller (mesh 0.20-0.40 mm) and larger (mesh 0.40-0.63 mm) size fractions. A portion of the wood components were also subjected to hydrothermal extraction (HE). Composite samples with these different wood components, polypropylene (PP) matrix, and maleated PP (MAPP) as coupling agent (50/48/2 wood/PP/MAPP ratio by weight) were then prepared by using a Brabender mixer followed by hot pressing. The matching micromorphology of the composites before and after the soaking-drying cycles was analyzed using a surface preparation technique based on ultraviolet-laser ablation combined with scanning electron microscopy. The results of the water absorption tests showed, as hypothesized, a significantly reduced water absorption and resulting thickness swelling at the end of a soaking cycle for the TMWPCs compared with the controls (UWPCs). The water absorption was reduced with about 50-70% for TMWPC and 60-75% for HE-TMWPC. The thickness swelling for TMWPCs was reduced with about 40-70% compared with the controls. Similarly, the WPCs with HE-UW components absorbed about 20-45% less moisture and showed a reduced thickness swelling of about 25-40% compared with the controls. These observations also were in agreement with the micromorphology analysis of the composites before and after the moisture cycling which showed a more pronounced wood-plastic interfacial cracking (de-bonding) as well as other microstructure changes in the controls compared with those prepared with TMW and HE-UW components. Based on these observations, it is suggested that these potential bio-based building materials show increased potential durability for applications in harsh outdoor environments, in particular TMWPCs with a well-defined and comparably small size fractions of TMW components.
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| 22. |
- Källbom, Susanna, et al.
(författare)
-
Wood-plastic composites made from thermally modified spruce wood components and effects of exposure to water-soaking-drying cycles
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The over-all aim of this work is to gain more insight on the potential to use thermally modified wood (TMW) components in wood-thermoplastic composites (WPCs), ie a new type of biobased building material, here defined as TMWPCs, assumed to have significantly increased moisture resistance and durability related to conventional WPCs. The specific objective was to prepare lab-scale TMWPCs and WPC controls with unmodified wood (UW), and to expose these samples to a series of severe water-soaking-drying cycles to study the effects on the water sorption behavior and resulting dimensional and micromorphology changes. TMW was prepared by thermal modification of a spruce board in an atmosphere of superheated steam at atmospheric pressure with a peak temperature of 210°C (also matched with an UW board as control). TMW and UW components were then prepared by a Wiley mill and thereafter sifted into a smaller (0.20-0.40 mm) and a larger (0.40-0.63 mm) size fraction. A portion of the wood components were also hot-water extracted (HE) with liquid hot-water. Composite samples with these different wood components, polypropylene (PP) matrix, and maleated PP (MAPP) as coupling agent (50/48/2 wood/PP/MAPP ratio) were then prepared by using a Brabender mixer followed by hot-pressing. The matching micromorphology of the composites before and after the soaking-drying cycles was analyzed using a surface preparation technique based on UV-laser ablation combined with scanning electron microscopy (SEM). An effort was also made to study the wood-thermoplastic interfacial behavior in the composites by dynamic mechanical analysis (DMA). The results of the water absorption tests showed, as hypothesized, a significantly reduced water absorption and resulting thickness swelling for the TMWPCs compared with the controls. Similarly, the WPCs with HE-UW components showed a significant reduction in water absorption and thickness swelling compared with the controls. In contrast, the samples with HE-TMW components resulted in only minor moisture property changes. These observations were also in agreement with the micromorphology analysis of the composites before and after the moisture cycling which showed a more pronounced wood-plastic interfacial cracking (de-bonding) as well as other microstructure changes in the controls compared with those prepared with TMW and HE-UW components. The DMA indicated better dispersion and increased interfacial interaction for the WPCs with UW components with the smaller size fraction compared with the larger size fraction. The loss modulus and storage modulus were overall reduced for samples with HE and TMW components compared with those with UW components. Based on these observations it is suggested that a potential biobased building material with increased durability for applications in harsh outdoor environments may be tailored as a TMWPC with a well-defined and comparably small size fractions of TMW components.
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| 23. |
- Laine, Kristiina, et al.
(författare)
-
Acetylation and densification of wood
- 2015
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study was to explore the possibility to surface densify acetylated solid wood. The aim of surface densification is to improve mechanical properties, such as hardness, at the very surface of wood where the property improvements are mostly needed (e.g. in flooring and decking). However, when subjected to moisture, surface densified wood may swell back almost to the original dimensions. Therefore, acetylated and non-acetylated wood was surface densified in order to investigate whether the dimensional stability of densified wood may be improved by pre-acetylation. Surface densification was performed by compressing the acetylated radiate pine samples between metal plates with only one side heated (150°C) in order to target the deformation to one surface only. The original thickness of the samples was 20 mm and the target thickness 18 mm which was controlled by metal stops. The recovery of the deformation (set-recovery) was measured by soaking the samples in water and measuring the oven-dry thickness before and after soaking in repeated cycles. It was found that acetylated wood may be surface densified and indeed the set-recovery of the pre-acetylated wood was significantly lower (17.4 %) compared to non-acetylated wood (72.8 %). Further studies in adjusting the process parameters might lead to even higher reduction in set-recovery.
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| 24. |
- Laine, Kristiina, et al.
(författare)
-
Hardness, set-recovery and micromorphology studies of densified and thermally modified wood
- 2015
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of the work reported in this paper was to increase the density of Scots pine wood in order to improve its hardness. Density was increased by compressing the porous structure of wood between heated metal plates in the radial direction by 40, 50 or 60% of the thickness. The compressed state was stabilised by thermally modifying (TM) the samples at 200 °C under steam conditions for 2, 4 or 6h. Set-recovery was almost eliminated (<1%) with TM of 6h for samples compressed 40 and 50%. It was discovered that hardness of densified wood was in some cases even three times higher compared to untreated wood. However, the hardness of the densified, non-TM wood was reduced after soaking and drying back to the original untreated level, while TM of 4 and 6h maintained an increased level of hardness.
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| 25. |
- Laine, Kristiina, et al.
(författare)
-
Micromorphological studies of surface densified wood
- 2014
-
Ingår i: Journal of Materials Science. - : Springer Science and Business Media LLC. - 0022-2461 .- 1573-4803. ; 49:5, s. 2027-2034
-
Tidskriftsartikel (refereegranskat)abstract
- Scots pine (Pinus sylvestris L.) wood was surface densified in its radial direction in an open press with one heated plate to obtain a higher density on the wood surface whilst retaining the overall thickness of the sample. This study investigated the effect of temperature (100, 150 and 200 A degrees C) and press closing speed (5, 10 and 30 mm/min, giving closing times of 60, 30 and 10 s, respectively) on the micromorphology of the cell-wall, as well as changes occurring during set-recovery of the densified wood. The micromorphology was analysed using scanning electron microscopy (SEM) combined with a sample preparation technique based on ultraviolet-excimer laser ablation. Furthermore, the density profiles of the samples were measured. Low press temperature (100 A degrees C) and short closing time (10 s) resulted in more deformation through the whole thickness, whilst increasing the temperature (150 and 200 A degrees C) and prolonging the closing time (30 and 60 s) enabled more targeted deformation closer to the heated plate. The deformation occurred in the earlywood regions as curling and twisting of the radial cell-walls, however, no apparent cell-wall disruption or internal fracture was observed, even at low temperatures and fast press closing speed, nor after soaking and drying of the samples. In the SEM-analysis after soaking and drying, it was noticed that the cells did not completely recover their original form. Thus, part of the deformation was considered permanent perhaps due to viscoelastic flow and plastic deformation of the cell-wall components.
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| 26. |
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| 27. |
- Laine, Kristiina, et al.
(författare)
-
Wood densification and thermal modification: hardness, set-recovery and micromorphology
- 2016
-
Ingår i: Wood Science and Technology. - : Springer Berlin/Heidelberg. - 0043-7719 .- 1432-5225. ; 50:5, s. 883-894
-
Tidskriftsartikel (refereegranskat)abstract
- The density of wood can be increased by compressing the porous structure under suitable moisture and temperature conditions. One aim of such densification is to improve surface hardness, and therefore, densified wood might be particularly suitable for flooring products. After compression, however, the deformed wood material is sensitive to moisture, and in this case, recovered up to 60 % of the deformation in water-soaking. This phenomenon, termed set-recovery, was reduced by thermally modifying the wood after densification. This study presents the influence of compression ratio (CR = 40, 50, 60 %) and thermal modification time (TM = 2, 4, 6 h) on the hardness and set-recovery of densified wood. Previously, set-recovery has mainly been studied separately from other properties of densified wood, while in this work, set-recovery was also studied in relation to hardness. The results show that set-recovery was almost eliminated with TM 6 h in the case of CR 40 and 50 %. Hardness significantly increased due to densification and even doubled compared to non-densified samples with a CR of 50 %. Set-recovery reduced the hardness of densified (non-TM) wood back to the original level. TM maintained the hardness of densified wood at an increased level after set-recovery. However, some reduction in hardness was recorded even if set-recovery was almost eliminated.
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| 28. |
- Low, Yen Ling, et al.
(författare)
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Multi-Variant Pathway Association Analysis Reveals the Importance of Genetic Determinants of Estrogen Metabolism in Breast and Endometrial Cancer Susceptibility
- 2010
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 6:7, s. e1001012-
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway, polymorphisms within the pathway have not been consistently associated with these cancers. We posit that this is due to the complexity of multiple weak genetic effects within the metabolic pathway that can only be effectively detected through multi-variant analysis. We conducted a comprehensive association analysis of the estrogen metabolic pathway by interrogating 239 tagSNPs within 35 genes of the pathway in three tumor samples. The discovery sample consisted of 1,596 breast cancer cases, 719 endometrial cancer cases, and 1,730 controls from Sweden; and the validation sample included 2,245 breast cancer cases and 1,287 controls from Finland. We performed admixture maximum likelihood (AML)-based global tests to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three sub-pathways for androgen synthesis, androgen-to-estrogen conversion, and estrogen removal. In the discovery sample, although no single polymorphism was significant after correction for multiple testing, the pathway-based AML global test suggested association with both breast (rho(global) = 0.034) and endometrial (rho(global) = 0.052) cancers. Further testing revealed the association to be focused on polymorphisms within the androgen-to-estrogen conversion sub-pathway, for both breast (rho(global) = 0.008) and endometrial cancer (rho(global) = 0.014). The sub-pathway association was validated in the Finnish sample of breast cancer (rho(global) = 0.015). Further tumor subtype analysis demonstrated that the association of the androgen-to-estrogen conversion sub-pathway was confined to postmenopausal women with sporadic estrogen receptor positive tumors (rho(global) = 0.0003). Gene-based AML analysis suggested CYP19A1 and UGT2B4 to be the major players within the sub-pathway. Our study indicates that the composite genetic determinants related to the androgen-estrogen conversion are important for the induction of two hormone-associated cancers, particularly for the hormone-driven breast tumour subtypes.
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| 29. |
- Mark, Kristiina, et al.
(författare)
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Testing morphology-based delimitation of Vulpicida juniperinus and V. tubulosus (Parmeliaceae) using three molecular markers.
- 2012
-
Ingår i: Lichenologist. - 0024-2829. ; 44:6, s. 757-772
-
Tidskriftsartikel (refereegranskat)abstract
- The delimitation of two morphologically similar and not easily separable Vulpicida species,V. juniperinus and V. tubulosus, is analyzed using nuclear ITS and Mcm7, and mitochondrial SSU DNA sequences. Seventy-nine Vulpicida specimens, most from the two focal taxa, are included in the three-locus gene tree. The results from Bayesian and parsimony analyses are presented. There are strong conflicts between the single locus gene trees. Vulpicida juniperinus and V. tubulosus are divided into two clearly distinguished groups in the ITS and concatenated B/MCMC tree. However, these species are mixed in both clades, appearing polyphyletic. Currently accepted V. juniperinus and V. tubulosus are not distinct according to the loci studied. Vulpicida pinastri appears monophyletic based on the available sequences.
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| 30. |
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| 31. |
- Portugal, Ana Maria, et al.
(författare)
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Infants' looking preferences for social versus non-social objects reflect genetic variation
- 2024
-
Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 8:1, s. 115-124
-
Tidskriftsartikel (refereegranskat)abstract
- To what extent do individual differences in infants’ early preference for faces versus non-facial objects reflect genetic and environmental factors? Here in a sample of 536 5-month-old same-sex twins, we assessed attention to faces using eye tracking in two ways: initial orienting to faces at the start of the trial (thought to reflect subcortical processing) and sustained face preference throughout the trial (thought to reflect emerging attention control). Twin model fitting suggested an influence of genetic and unique environmental effects, but there was no evidence for an effect of shared environment. The heritability of face orienting and preference were 0.19 (95% confidence interval (CI) 0.04 to 0.33) and 0.46 (95% CI 0.33 to 0.57), respectively. Face preference was associated positively with later parent-reported verbal competence (β = 0.14, 95% CI 0.03 to 0.25, P = 0.014, R2 = 0.018, N = 420). This study suggests that individual differences in young infants’ selection of perceptual input—social versus non-social—are heritable, providing a developmental perspective on gene–environment interplay occurring at the level of eye movements.
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| 32. |
- Portugal, Ana Maria, et al.
(författare)
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Pupil size and pupillary light reflex in early infancy : heritability and link to genetic liability to schizophrenia
- 2022
-
Ingår i: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 63:9, s. 1068-1077
-
Tidskriftsartikel (refereegranskat)abstract
- Background Measures based on pupillometry, such as the pupillary light reflex (PLR) and baseline pupil size, reflect physiological responses linked to specific neural circuits that have been implicated as atypical in some psychiatric and neurodevelopmental conditions.MethodsWe investigated the contribution of genetic and environmental factors to the baseline pupil size and the PLR in 510 infant twins assessed at 5?months of age (281 monozygotic and 229 dizygotic pairs), and its associations with common genetic variants associated with neurodevelopmental (autism spectrum disorder and attention deficit hyperactivity disorder) and mental health (bipolar disorder, major depressive disorder and schizophrenia) conditions using genome-wide polygenic scores (GPSs).ResultsUnivariate twin modelling showed high heritability at 5?months for both pupil size (h2?=?.64) and constriction in response to light (h2?=?.62), and bivariate twin modeling indicated substantial independence between the genetic factors influencing each (rG?=?.38). A statistically significant positive association between infant tonic pupil size and the GPS for schizophrenia was found (??=?.15, p?=?.024), while there was no significant association with the GPS for autism or any other GPSs.ConclusionsThis study shows that some pupil measures are highly heritable in early infancy, although substantially independent in their genetic etiologies, and associated with common genetic variants linked to schizophrenia. It illustrates how genetically informed studies of infants may help us understand early physiological responses associated with psychiatric disorders which emerge much later in life.
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| 33. |
- Reed, Mark, et al.
(författare)
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Policy and Governance Options for Peatlands Conservation, Restoration and Sustainable Management
- 2022
-
Ingår i: Global Peatlands Assessment. - : United Nations Environment Programme. - 9789280739916 ; , s. 252-271
-
Bokkapitel (refereegranskat)abstract
- In an era of high uncertainty, rapid environmental change, and increased recognition of the coupling of social and ecological systems, it is clear that there are limitations to current peatland policy and governance. As policy goals, and biophysical, social and political conditions differ between locations, the governance of peatlands needs to be tailored to each national, regional, and local context. This governance must also be adjusted for the needs and interests of the human populations and other species that depend upon these habitats. The adoption of gender-responsive approaches that take into account the needs of both women and men especially those from lower socioeconomic status, are thus crucial if we are to make progress towards environmental sustainability.This chapter reviews a range of policy and governance instruments that can halt further degradation and destruction of peatlands and facilitate their conservation, restoration and sustainable management.
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| 34. |
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| 35. |
- Saag, Lehti, et al.
(författare)
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The Arrival of Siberian Ancestry Connecting the Eastern Baltic to Uralic Speakers further East
- 2019
-
Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 29:10, s. 1701-
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we compare the genetic ancestry of individuals from two as yet genetically unstudied cultural traditions in Estonia in the context of available modern and ancient datasets: 15 from the Late Bronze Age stone-cist graves (1200-400 BC) (EstBA) and 6 from the Pre-Roman Iron Age tarand cemeteries (800/500 BC-50 AD) (EstIA). We also included 5 Pre-Roman to Roman Iron Age Ingrian (500 BC450 AD) (IngIA) and 7 Middle Age Estonian (1200-1600 AD) (EstMA) individuals to build a dataset for studying the demographic history of the northern parts of the Eastern Baltic from the earliest layer of Mesolithic to modern times. Our findings are consistent with EstBA receiving gene flow from regions with strong Western hunter-gatherer (WHG) affinities and EstIA from populations related to modern Siberians. The latter inference is in accordance with Y chromosome (chrY) distributions in present day populations of the Eastern Baltic, as well as patterns of autosomal variation in the majority of the westernmost Uralic speakers [1-5]. This ancestry reached the coasts of the Baltic Sea no later than the mid-first millennium BC; i.e., in the same time window as the diversification of west Uralic (Finnic) languages [6]. Furthermore, phenotypic traits often associated with modern Northern Europeans, like light eyes, hair, and skin, as well as lactose tolerance, can be traced back to the Bronze Age in the Eastern Baltic.
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| 36. |
- Schwensen, Jakob F., et al.
(författare)
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The epidemic of methylisothiazolinone : A European prospective study
- 2017
-
Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873. ; 76:5, s. 272-279
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of methylisothiazolinone (MI) in cosmetic products has caused an unprecedented epidemic of MI contact allergy. Current data concerning exposures at a European level are required. Objectives: To describe demographics and MI exposures for European patients with MI contact allergy. Methods: Eleven European dermatology departments from eight European countries prospectively collected data between 1 May and 31 October 2015 among consecutive patients who had positive patch test reactions to MI (2000ppm aq.). Results: A total of 6.0% (205/3434; range 2.6-13.0%) of patients had positive patch test reactions to MI. Dermatitis most frequently affected the hands (43.4%), face (32.7%), arms (14.6%), and eyelids (11.7%); 12.7% had widespread dermatitis. For 72.7% (149/205), MI contact allergy was currently relevant mainly because of exposure to cosmetic products (83.2%; 124/149). Of these 124 patients, 19.5% were exposed to leave-on and rinse-off cosmetic products, 24.8% only to leave-on cosmetic products and 38.9% only to rinse-off cosmetic products containing MI or methylchloroisothiazolinone/MI. The majority of these (79%) noted onset of their dermatitis between 2013 and 2015. Fifteen patients (7.3%) had previously experienced allergic reactions when they were in newly painted rooms. Conclusion: Clinically relevant MI contact allergy remains prevalent across European countries, mainly because of exposure to rinse-off and leave-on cosmetic products.
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| 37. |
- Seligman, Mark, et al.
(författare)
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Tracking Morphological and Semantic Co-occurrences in Spontaneous Dialogues
- 1999
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In the processing of spontaneous language, information concerning discourse-level co-occurrences of words or morphemes - relatively long-term predictions on the scale of several utterances - may help to reduce perplexity in speech recognition, facilitate lexical disambiguation, and contribute to topic tracking. This working paper describes a new set of facilities for tracking lexical co-occurrences. The major innovation is the use of semantic smoothing: we track co-occurrences of semantic tokens associated with words or morphs in addition to co-occurrences of the words or morphs themselves. Such smoothing offers an approach to the problem of data sparseness: it is possible to retrieve reasonable semantically-mediated associations for morphs not in the training corpus. We report on preliminary experiments with a corpus of morphologically-tagged transcripts of 16 spontaneous Japanese dialogues concerning direction-finding and hotel arrangements. We close with discussion of lexical disambiguation and topic tracking as they relate to co-occurrence networks.
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| 38. |
- Stevens, Kristen N, et al.
(författare)
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19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
-
Tidskriftsartikel (refereegranskat)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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| 39. |
- Vahtikari, Katja, et al.
(författare)
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The influence of extractives on the sorption characteristics of Scots pine (Pinus sylvestris L.)
- 2017
-
Ingår i: Journal of Materials Science. - : Springer. - 0022-2461 .- 1573-4803. ; 52:18, s. 10840-10852
-
Tidskriftsartikel (refereegranskat)abstract
- The sorption behaviour of extracted and un-extracted Scots pine (Pinus sylvestris L.) heartwood was analysed using dynamic vapour sorption apparatus. In addition to the sorption isotherm and hysteresis, the moisture increments and decrements were determined as well as the rate of sorption. Parallel exponential kinetics model was used for further analysis. The effect of cyclic humidity loading on the sorption characteristics was studied by exposing samples to ten repeated sorption cycles and by determining the amount of accessible hydroxyl (OH) groups before and after the cyclic humidity loading. Removal of extractives led to an increase in EMC both in adsorption and in desorption. Hysteresis decreased due to the removal of extractives. Cyclic humidity loading reduced the sorptive capacity of wood material for both extracted and un-extracted wood, but was more pronounced in un-extracted wood. However, despite the decrease in the sorptive capacity, the amount of accessible OH groups increased after ten repeated dry-humid cycles.
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| 40. |
- Viktorsson, Charlotte, et al.
(författare)
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Preferential looking to eyes versus mouth in early infancy : heritability and link to concurrent and later development
- 2023
-
Ingår i: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 64:2, s. 311-319
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFrom birth, infants orient preferentially to faces, and when looking at the face, they attend primarily to eyes and mouth. These areas convey different types of information, and earlier research suggests that genetic factors influence the preference for one or the other in young children. MethodsIn a sample of 535 5-month-old infant twins, we assessed eye (relative to mouth) preference in early infancy, i.e., before neural systems for social communication and language are fully developed. We investigated the contribution of genetic and environmental factors to the preference for looking at eyes, and the association with concurrent traits and follow-up measures. ResultsEye preference was independent from all other concurrent traits measured, and had a moderate-to-high contribution from genetic influences (A = 0.57; 95% CI: 0.45, 0.66). Preference for eyes at 5 months was associated with higher parent ratings of receptive vocabulary at 14 months. No statistically significant association with later autistic traits was found. Preference for eyes was strikingly stable across different stimulus types (e.g., dynamic vs. still), suggesting that infants' preference at this age does not reflect sensitivity to low-level visual cues. ConclusionsThese results suggest that individual differences in infants' preferential looking to eyes versus mouth to a substantial degree reflect genetic variation. The findings provide new leads on both the perceptual basis and the developmental consequences of these attentional biases.
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| 41. |
- Yang, Xin, et al.
(författare)
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Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families
- 2020
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 38:7, s. 674-685
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
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| 42. |
- Zanti, Maria, et al.
(författare)
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A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2
- 2023
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
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| 43. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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