| 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. |
- Downey, Harriet, et al.
(författare)
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Training future generations to deliver evidence-based conservation and ecosystem management
- 2021
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Ingår i: Ecological Solutions and Evidence. - : Wiley. - 2688-8319. ; 2:1
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Forskningsöversikt (refereegranskat)abstract
- 1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis.2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice.3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses.4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.
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| 3. |
- 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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| 4. |
- Hein, Sascha, et al.
(författare)
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Psychological and Sociocultural Adaptation of Children Adopted from Russia and their Associations with Pre-Adoption Risk Factors and Parenting
- 2017
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Ingår i: Journal of Child and Family Studies. - : SPRINGER. - 1062-1024 .- 1573-2843. ; 26:10, s. 2669-2680
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Tidskriftsartikel (refereegranskat)abstract
- We investigated academic and behavioral outcomes of internationally adopted children and the associations between these outcomes and age at adoption, time spent in the adoptive family, and parenting. At two time points (T1 and T2, similar to 15 months apart), we examined early academic skills (school readiness), and parent-reported behavioral adjustment (internalizing and externalizing behavior) and adaptive functioning of a sample of 75 children (45.9% boys, mean age = 5.17 years) adopted from Russia into US families. We also collected parents' self-assessments of their parenting at T1. Children who were adopted at a younger age showed higher levels of early academic skills. Correlations between age at adoption and other outcomes were overall small and mostly non-significant. However, adoptees' academic and behavioral progress differed notably in several respects. Specifically, adoptees improved in early academic skills over time, whereas, as a group, their adaptive functioning and behavioral adjustment remained stable within the normal range. Early academic skills were not related to behavioral adjustment at each time point and over time. The time spent in the adoptive family was positively related to early academic skills at T2. Whereas outcomes showed little to no relation to parenting as reported by mother and father separately, higher discrepancies between mothers' and fathers' reports of positive parenting were related to higher levels of behavioral symptoms and lower levels of adaptive skills at T2. These differential results may be explained in part by drawing upon the notion of dissociated domains of psychological and sociocultural adaptation and acculturation, outlined in the immigration literature. These results also bring to light the possible importance of between-parent consistency in parenting for adoptees' behavioral outcomes.
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| 5. |
- Rakhlin, Natalia, et al.
(författare)
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Language development of internationally adopted children : Adverse early experiences outweigh the age of acquisition effect
- 2015
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Ingår i: Journal of Communication Disorders. - : Elsevier BV. - 0021-9924 .- 1873-7994. ; 57:SI, s. 66-80
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Tidskriftsartikel (refereegranskat)abstract
- We compared English language and cognitive skills between internationally adopted children (IA; mean age at adoption=2.24, SD=1.8) and their non-adopted peers from the US reared in biological families (BF) at two time points. We also examined the relationships between outcome measures and age at initial institutionalization, length of institutionalization, and age at adoption. On measures of general language, early literacy, and non-verbal IQ, the IA group performed significantly below their age-peers reared in biological families at both time points, but the group differences disappeared on receptive vocabulary and kindergarten concept knowledge at the second time point. Furthermore, the majority of children reached normative age expectations between 1 and 2 years post-adoption on all standardized measures. Although the age at adoption, age of institutionalization, length of institutionalization, and time in the adoptive family all demonstrated significant correlations with one or more outcome measures, the negative relationship between length of institutionalization and child outcomes remained most robust after controlling for the other variables. Results point to much flexibility and resilience in children's capacity for language acquisition as well as the potential primacy of length of institutionalization in explaining individual variation in IA children's outcomes.LEARNING OUTCOMES: (1) Readers will be able to understand the importance of pre-adoption environment on language and early literacy development in internationally adopted children. (2) Readers will be able to compare the strength of the association between the length of institutionalization and language outcomes with the strength of the association between the latter and the age at adoption. (3) Readers will be able to understand that internationally adopted children are able to reach age expectations on expressive and receptive language measures despite adverse early experiences and a replacement of their first language with an adoptive language.
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| 6. |
- Rakhlin, Natalia, et al.
(författare)
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Sources of Heterogeneity in Developmental Outcomes of Children With Past and Current Experiences of Institutionalization in Russia : A Four-Group Comparison
- 2017
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Ingår i: American Journal of Orthopsychiatry. - : AMER PSYCHOLOGICAL ASSOC. - 0002-9432 .- 1939-0025. ; 87:3, s. 242-255
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Tidskriftsartikel (refereegranskat)abstract
- The present study sought to compare 4 groups of age-and gender-matched children-(a) those reared in institutions for children without parental care in Russia; (b) those raised by their biological parents in Russia; (c) those adopted to the United States from Russian institutions; and (d) those born in the United States and raised by their biological parents-on indicators of cognition, language, and early learning. In addition, we aimed to compare the effects of the length of time spent in an institution, the age of initial placement in an institution, the age at adoption, and pre-institutional risk factors (i.e., prenatal substance exposure and prematurity and low birth weight) on the above-mentioned outcomes in the 2 groups of children with institutionalization experiences. Our results confirm previous reports demonstrating negative consequences of institutionalization and substantial ameliorating effects of adoption. They also underscore the complexity of the effects of institutionalization and adoption, showing that they are intertwined with the effects of pre-institutional risk factors.
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| 7. |
- 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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