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- Berndt, Sonja I., et al.
(författare)
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Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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| 2. |
- Berndt, Sonja I., et al.
(författare)
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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
- 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
- Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
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| 3. |
- Conde, Lucia, et al.
(författare)
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Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:8, s. 661-664
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
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| 6. |
- Goldin, Stephen, 1948-
(författare)
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Living in the present with the past : mental health of Bosnian refugee children in Sweden
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The negative impact of war on child mental health has been repeatedly documented. Still, the majority of children exposed to ethnic and political violence show no signs of clinical disorder. In Western countries of exile, these findings have prompted a variety of attempts to evaluate refugee children, in the hope of identifying and offering support to those children “at risk”. This study critically examines one such attempt. The aims are fourfold: 1. to describe the range and pattern of child trauma-stress exposure and mental health reactions as captured on clinician semi-structured interview; 2. to critically compare clinician assessment with independent parent, child and teacher reports; 3. to identify factors of potential risk or protective import for child mental health; 4. to draw clinical implications: from whom and by what means can children at risk be reasonably identified? The target of our study was the entire population of Bosnian-Serbian-Croatian speaking child refugee families assigned to Umeå and surrounding municipalities during 1994-95. Fifty families, containing 90 children aged one month to 20 years, were included in the study. Assessment occurred in two phases. First, a semi-structured interview was conducted that inquired broadly as to the child’s family background, trauma-stress exposure, emotional-behavioral problems, patterns of family functioning, and future hopes. Second, standardized self-report questionnaires were administered, separately to parent and child, to provide alternative appraisal of the child’s war exposure, mental health symptoms, coping strategies, and social network. Teacher evaluation of child cognitive-social functioning as well as emotional-behavioral problems was also obtained. Clinician semi-structured interview revealed the child’s pre-war period as preponderantly good, and provided richly detailed narratives of child exposure during war and resettlement that clustered into a limited number of type-stories. Independent parent assessment captured the same broad strokes of child war exposure; but both approaches – fixed questionnaire and semi-structured interview – showed specific areas of blindness. Teenage self-report offered a disparate but equally rich account of war exposure, while that of primary school child was significantly less detailed. Nearly half of the study children (48%) were identified on clinician interview with one or more mental health problem “demanding further attention”. Depressiveness was the single most prevalent symptom (31%), followed by posttraumatic reactions (23%) and anxiety-regressiveness (15%). Independent symptom appraisal by parent and primary school child was largely concordant with that of clinician, while teenagers made similar assessment as to who was in distress, but defined the nature of that distress differently. Teacher report stood apart, identifying fewer inward emotional problems and asserting the cognitive-social competence of the vast majority of study children. Trauma-stress exposure during both war and resettlement presented as an unequivocal risk to mental health, but accounted for only part of outcome variance. Additional factors of strong import related broadly to “living in the present”. Parent impairment of daily routines, child dissatisfaction with school and an ongoing quarrelsome relationship presented as risk factors. Protection was associated with parent maintenance of a warm family climate and of concrete physical-emotional caring, child social ties to physically present others, including teacher; and above all, a family sense of hope for the future. Results support the general robustness of our semi-structured approach. Exploring the child’s present well-being in narrative relation to past and future, our assessment captured and gave meaning to the complexity of child exposure and behavior. At the same time, independent parent and child appraisals provided an additional richness to the retelling and evaluation of child experience. Particularly the apartness of teacher report underscores the need to incorporate an outside-world vantage point in the process of risk assessment.
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| 7. |
- Goldin, Stephen, et al.
(författare)
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Mental health of Bosnian refugee children : A comparison of clinician appraisal with parent, child and teacher reports
- 2008
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Ingår i: Nordic Journal of Psychiatry. - Oslo : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 62:3, s. 204-216
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Tidskriftsartikel (refereegranskat)abstract
- This study compares clinician appraisal of Bosnian refugee children with independent parent, child and teacher reports. From whom and by what means can children “at risk” be reasonably identified? Forty-eight Bosnian refugee children (aged 7-20), resettled in Sweden 1994-95, were assessed clinically by means of a semi-structured interview. Thereafter, standardized mental health questionnaires were administered to parents (Achenbach's Child Behavior Checklist), children (Achenbach's Youth Self-Report and Macksoud's Posttraumatic Stress Reaction Checklist) and teachers (clinician designed School Competence Scale and Achenbach's Teacher's Report Form). On clinician interview, nearly half of the children (48%) were identified with one or more mental health problem “demanding further attention”. Depressiveness was the single most prevalent symptom (31%); followed by post-traumatic stress (23%), and anxiety-regressiveness (15%). At the same time, 75% of the children were rated by teachers as “quite competent” in school. Parent, child and clinician appraisals of primary school children showed broad similarities. Teachers reported a similar prevalence of child distress, but identified different symptoms and different children demanding attention. Evaluation of teenage youths showed greater disparity: teenagers labeled their own symptoms more often as post-traumatic stress reactions and teachers identified few youths in need of attention. Inter-relatedness among parent, child and clinician appraisals supports the robustness of our semi-structured interview. At the same time, apartness of teacher report underscores the need to incorporate an outside-world vantage point in the process of risk assessment. Also, a more concrete presentation of post-traumatic stress reactions and a higher “further attention” threshold for inward emotional problems seem called for.
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| 10. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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