| 1. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
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| 3. |
- D'Onofrio, Brian M., et al.
(författare)
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Translational Epidemiologic Approaches to Understanding the Consequences of Early-Life Exposures
- 2016
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Ingår i: Behavior Genetics. - New York, USA : Springer. - 0001-8244 .- 1573-3297. ; 46:3, s. 315-328
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Forskningsöversikt (refereegranskat)abstract
- Prominent developmental theories posit a causal link between early-life exposures and later functioning. Yet, observed associations with early exposures may not reflect causal effects because of genetic and environmental confounding. The current manuscript describes how a systematic series of epidemiologic analyses that combine several genetically-informative designs and statistical approaches can help distinguish between competing theories. In particular, the manuscript details how combining the use of measured covariates with sibling-comparisons, cousin-comparisons, and additional designs can help elucidate the sources of covariation between early-life exposures and later outcomes, including the roles of (a) factors that are not shared in families, including a potential causal effect of the exposure; (b) carryover effects from the exposure of one child to the next; and (c) familial confounding. We also describe key assumptions and how they can be critically evaluated. Furthermore, we outline how subsequent analyses, including effect decomposition with respect to measured, plausible mediators, and quantitative genetic models can help further specify the underlying processes that account for the associations between early-life exposures and offspring outcomes.
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| 4. |
- Ekeblad, Sara, et al.
(författare)
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Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution
- 2008
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 14:23, s. 7798-7803
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Unequivocal pathologic markers for the prognosis of pancreatic endocrine tumors are often lacking. Suggestions for prognostic guidance include the WHO classification. Recently, a tumor-node-metastasis (TNM) staging system was proposed. We evaluate this system, as well as assess other potential prognostic factors such as tumor Ki67, size, endocrine syndrome, heredity, body mass index (BMI), and plasma chromogranin A, in a large patient material treated at a single institution. EXPERIMENTAL DESIGN: A total of 324 patients with pancreatic endocrine tumor, consecutively diagnosed and treated at a tertiary referral center, were retrospectively evaluated. Median follow-up was 54 months (range, 1-423 months). Patient and tumor data were extracted from medical records. Univariate and multivariate analyses were done to recognize factors of prognostic value. RESULTS: The median overall survival was 99 months (95% confidence interval, 81-117). Five- and 10-year survival rates were 64% and 44%, respectively. In univariate analysis, TNM stage, radical surgery, WHO classification, nonfunctioning tumor, Ki67 ≥2%, chromogranin A ≥3 times the upper normal limit, BMI <20 kg/m2, sporadic tumor, tumor size, and referral from our primary uptake area had a significant prognostic effect. In multivariate analysis, TNM stage, WHO classification, radical surgery, and Ki67 ≥2% retained their significance. Having a nonfunctioning tumor was not an independent marker of poor prognosis and neither was heredity. CONCLUSIONS: The recently suggested TNM staging system emerged as a useful clinical tool.
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| 7. |
- Higueras-Fresnillo, Sara, et al.
(författare)
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Associations of psychological factors with atherosclerosis and cardiovascular health in middle-age : the population-based Swedish CArdioPulmonary bioImage study (SCAPIS)
- 2024
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiovascular disease (CVD) is a major global health issue, primarily caused by atherosclerosis. Psychological factors may play a role in the development and progression of CVD. However, the relationship between psychological factors and atherosclerosis is complex and poorly understood. This study, therefore, aimed to examine the association of psychological factors with (i) coronary and carotid atherosclerosis and (ii) cardiovascular health according to Life’s Essential 8, in a large Swedish cohort.Methods: This study utilized data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), a large population-based project including individuals aged 50 to 65 years. Several psychological factors were analysed: general stress, stress at work, financial stress, major adverse life events, locus of control, feeling depressed, and depression. Coronary atherosclerosis was assessed as the degree of stenosis by coronary computed tomography angiography (CCTA) and coronary artery calcification (CAC) scores. Carotid atherosclerosis was examined using ultrasound. In addition, cardiovascular health was examined using the Life’s Essential 8 concept created by the American Heart Association, which includes four health behaviors and four health factors. Associations were examined through binomial logistic regression (atherosclerosis variables) and linear regression (Life’s Essential 8).Results: A total of 25,658 participants were included in the study. The presence of financial stress, higher locus of control, and depression was weakly associated with increased odds of CCTA stenosis, CAC ≥ 1 and the presence of carotid plaques (all odds ratios: 1.10–1.21, 95% CI: 1.02–1.32) after adjusting for sex, age, and study site. However, these associations were attenuated and not statistically significant after additional adjustments for socioeconomic factors and health behaviors. Conversely, we observed inverse associations between the worst category for all psychological factors and cardiovascular health according to Life’s Essential 8 score (all standardized β-Coefficient ≤-0.033, p < 0.001).Conclusion: While there were no strong and consistent associations between psychological factors and atherosclerosis, the consistent associations of psychological factors with cardiovascular health by Life’s Essential 8 may have relevance for future CVD risk. However, further studies are needed to elucidate the long-term effects of psychological factors on atherosclerosis development and cardiovascular health.
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| 8. |
- Higueras-Fresnillo, Sara, et al.
(författare)
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Associations of psychological factors with atherosclerosis and cardiovascular health in middle-age: the population-based Swedish CArdioPulmonary bioImage study (SCAPIS)
- 2024
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Ingår i: BMC Public Health. - : BMC. - 1471-2458. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Cardiovascular disease (CVD) is a major global health issue, primarily caused by atherosclerosis. Psychological factors may play a role in the development and progression of CVD. However, the relationship between psychological factors and atherosclerosis is complex and poorly understood. This study, therefore, aimed to examine the association of psychological factors with (i) coronary and carotid atherosclerosis and (ii) cardiovascular health according to Life's Essential 8, in a large Swedish cohort. Methods This study utilized data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), a large population-based project including individuals aged 50 to 65 years. Several psychological factors were analysed: general stress, stress at work, financial stress, major adverse life events, locus of control, feeling depressed, and depression. Coronary atherosclerosis was assessed as the degree of stenosis by coronary computed tomography angiography (CCTA) and coronary artery calcification (CAC) scores. Carotid atherosclerosis was examined using ultrasound. In addition, cardiovascular health was examined using the Life's Essential 8 concept created by the American Heart Association, which includes four health behaviors and four health factors. Associations were examined through binomial logistic regression (atherosclerosis variables) and linear regression (Life's Essential 8). Results A total of 25,658 participants were included in the study. The presence of financial stress, higher locus of control, and depression was weakly associated with increased odds of CCTA stenosis, CAC >= 1 and the presence of carotid plaques (all odds ratios: 1.10-1.21, 95% CI: 1.02-1.32) after adjusting for sex, age, and study site. However, these associations were attenuated and not statistically significant after additional adjustments for socioeconomic factors and health behaviors. Conversely, we observed inverse associations between the worst category for all psychological factors and cardiovascular health according to Life's Essential 8 score (all standardized beta-Coefficient <=-0.033, p < 0.001). Conclusion While there were no strong and consistent associations between psychological factors and atherosclerosis, the consistent associations of psychological factors with cardiovascular health by Life's Essential 8 may have relevance for future CVD risk. However, further studies are needed to elucidate the long-term effects of psychological factors on atherosclerosis development and cardiovascular health.
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| 9. |
- Klein, Alison P., et al.
(författare)
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Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 x 10(-8)). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PAN-DoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 x 10(-14)), rs2941471 at 8q21.11 (HNF4G, P = 6.60 x 10(-10)), rs4795218 at 17q12 (HNF1B, P = 1.32 x 10(-8)), and rs1517037 at 18q21.32 (GRP, P = 3.28 x 10(-8)). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
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| 10. |
- Sujan, Ayesha C., et al.
(författare)
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A Nation-Wide Swedish Cohort Study on Early Maternal Age at First Childbirth and Risk for Offspring Deaths, Accidents, and Suicide Attempts
- 2022
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Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 52:1, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- In a sample of over one million Swedish first-born offspring, we examined associations between early maternal age at first childbirth (MAFC; i.e., < 20 and 20-24 vs 25-29 years) and offspring non-accidental deaths, accidental deaths, deaths by suicide, non-fatal accidents, and suicide attempts. We included year of birth and several maternal and paternal characteristics as covariates and conducted maternal cousin comparisons to adjust for unmeasured confounding. Early MAFC (e.g., teenage childbearing) was associated with all outcomes, with the most pronounced risk elevation for accidental deaths [Hazard Ratio (HR) < 20 2.50, 95% confidence interval (CI) 2.23, 2.80], suicides (HR < 20 2.08, 95% CI 1.79, 2.41), and suicide attempts (HR < 20 2.85, 95% CI 2.71, 3.00). Adjusting for covariates and comparing cousins greatly attenuated associations (e.g., accidental deaths HR < 20 1.61, 95% CI 1.22, 2.11; suicides HR < 20 1.01, 95% CI 0.69, 1.47; and suicide attempts HR < 20 1.35, 95% CI 1.19, 1.52). A similar pattern emerged for non-accidental deaths and non-fatal accidents. Therefore, results indicated maternal background factors may be largely responsible for observed associations.
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