| 1. |
- Almqvist, Catarina, et al.
(författare)
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Association between parental age and asthma in a population-based register study
- 2015
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Ingår i: Journal of Allergy and Clinical Immunology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0091-6749 .- 1097-6825.
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Tidskriftsartikel (refereegranskat)abstract
- In a nationwide population-based study with family design, we found an association between decreasing parental age and asthma in early childhood. The effect was independent of familial and potentially confounding factors.
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| 2. |
- Almqvist, Catarina, et al.
(författare)
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Cohort profile : Swedish Twin Study on Prediction and Prevention of Asthma (STOPPA)
- 2015
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Ingår i: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a common childhood disease and several risk factors have been identified, however the impact of genes and environment is not fully understood. The aim of the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) is to identify environmental (birth characteristics and early life) and genetic (including epigenetic) factors as determinants for asthmatic disease. Based on the Child and Adolescent Twin Study in Sweden (parental interview at 9 or 12 years, N~23,900) and an asthma and/or wheezing algorithm, we identified a sample of monozygotic (MZ) and dizygotic (DZ) same-sexed twin pairs. The twin pairs were identified as asthma concordant (ACC), asthma discordant (ADC) and healthy concordant (HCC). A sample of 9- to 14-year-old twins and their parents were invited to participate in a clinical examination. Background characteristics were collected in questionnaires and obtained from the National Health Registers. A clinical examination was performed to test lung function and capacity (spirometry with reversibility test and exhaled nitric oxide) and collect blood (serology and DNA), urine (metabolites), feces (microbiota) and saliva (cortisol). In total, 376 twin pairs (752 individual twins) completed the study, response rate 52%. All participating twins answered the questionnaire and >90% participated in lung function testing, blood and saliva sampling. This article describes the design, recruitment, data collection, measures, background characteristics as well as ongoing and planned analyses in STOPPA. Potential gains of the study include the identification of biomarkers, the emergence of candidates for drug development and new leads for prevention of asthma and allergic disease.
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| 3. |
- Ferreira, Manuel A R, et al.
(författare)
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Eleven loci with new reproducible genetic associations with allergic disease risk.
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 143:2, s. 691-699
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever, and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities.OBJECTIVE: We sought to identify novel risk loci shared between asthma, hay fever, and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 subjects.METHODS: We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analyzed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 subjects from the UK Biobank study.RESULTS: Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P value of 2.5 × 10-6. Of these, 20 were also significantly associated (P < .05/30 = .0016) with disease risk in the replication sample, including 19 that were located in 11 loci not reported to contain allergy risk variants in previous GWASs. Among these were 9 genes with a known function that is directly relevant to allergic disease: FOSL2, VPRBP, IPCEF1, PRR5L, NCF4, APOBR, IL27, ATXN2L, and LAT. For 4 genes (eg, ATXN2L), a genetically determined decrease in gene expression was associated with decreased allergy risk, and therefore drugs that inhibit gene expression or function are predicted to ameliorate disease symptoms. The opposite directional effect was observed for 14 genes, including IL27, a cytokine known to suppress TH2 responses.CONCLUSION: Using a gene-based approach, we identified 11 risk loci for allergic disease that were not reported in previous GWASs. Functional studies that investigate the contribution of the 19 associated genes to the pathophysiology of allergic disease and assess their therapeutic potential are warranted.
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| 4. |
- Hedman, Anna M, et al.
(författare)
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Agreement between asthma questionnaire and health care register data
- 2018
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Ingår i: Pharmacoepidemiology & Drug Safety. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1053-8569 .- 1099-1557.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Risk factors and consequences of asthma can be studied using validated questionnaires. The overall objective of this study was to assess the agreement of parental-reported asthma related questions regarding their children against Swedish health care registers. Methods: We linked a population-based twin cohort of 27,055 children aged 9-12 years, to the Swedish Prescribed Drug Register, National Patient Register and the Primary care register. Parent-reported asthma was obtained from questionnaires and diagnoses and medication were retrieved from the registers. For the agreement between the questionnaire and the registers, Cohen’s kappa was estimated. Results The kappa of the ‘reported ever asthma’ against a ‘register-based ever asthma’ was 0.69 and 0.57 between the parental-‘reported doctor’s diagnosis’ and ‘register-based doctor’s diagnosis’ ’. The highest agreement between ‘reported current asthma’ and ‘register- based current asthma’ with at least one dispensed medication or a diagnosis applied to different time-windows was seen for an 18 month window (kappa=0.70). Conclusions We found that parent-reported asthma-related questions showed on average good agreement with the Swedish health care registers. This implies that in depth questionnaires with rich information on phenotypes are suitable proxies for asthma in general and can be used for health care research purposes.
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| 5. |
- Jelenkovic, Aline, et al.
(författare)
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Associations between birth size and later height from infancy through adulthood : An individual based pooled analysis of 28 twin cohorts participating in the CODATwins project
- 2018
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Ingår i: Early Human Development. - : Elsevier BV. - 0378-3782 .- 1872-6232. ; 120, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is evidence that birth size is positively associated with height in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. Aim: To analyze the associations of birth weight, length and ponderal index with height from infancy through adulthood within mono- and dizygotic twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 28 twin cohorts in 17 countries. The pooled data included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic) with information on birth weight and a total of 112,409 paired height measurements at ages ranging from 1 to 69 years. Birth length was available for 19,881 complete twin pairs, with a total of 72,692 paired height measurements. The association between birth size and later height was analyzed at both the individual and within-pair level by linear regression analyses. Results: Within twin pairs, regression coefficients showed that a 1-kg increase in birth weight and a 1-cm increase in birth length were associated with 1.14–4.25 cm and 0.18–0.90 cm taller height, respectively. The magnitude of the associations was generally greater within dizygotic than within monozygotic twin pairs, and this difference between zygosities was more pronounced for birth length. Conclusion: Both genetic and individual-specific environmental factors play a role in the association between birth size and later height from infancy to adulthood, with a larger role for genetics in the association with birth length than with birth weight.
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| 6. |
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| 7. |
- Silventoinen, Karri, et al.
(författare)
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Education in twins and their parents across birth cohorts over 100 years : an individual-level pooled analysis of 42 twin cohorts
- 2017
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Ingår i: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
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Tidskriftsartikel (refereegranskat)abstract
- Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
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| 8. |
- Smew, Awad I, et al.
(författare)
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Limited association between markers of stress during pregnancy and fetal growth in 'Born into Life' : a new prospective birth cohort
- 2018
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Ingår i: Acta Paediatrica: Nurturing the Child. - Stockholm : Karolinska Institutet, Institute of Environmental Medicine. - 0803-5253 .- 1651-2227.
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We aimed to investigate the associations between perceived maternal stress or salivary cortisol levels during pregnancy and birthweight. Methods: In 2010-2012, we recruited 92 women living in Stockholm, Sweden, and followed them from before conception and through pregnancy and childbirth. Their Perceived Stress Scale (PSS) scores and salivary cortisol levels were collected at 26-28 gestational weeks. Birthweight was collected from medical records. Linear regression analyses and Pearson correlations were performed between the PSS scores or cortisol levels and birthweight, respectively, adjusted for gestational age. Results: No significant associations were found between PSS scores or cortisol levels and birthweight. There was a trend towards higher salivary cortisol levels among infants with lower birthweights, and this effect was attenuated after adjusting for gestational age. Morning cortisol levels (r = -0.31, p = 0.01), the decline in cortisol levels (r = -0.26, p = 0.03) and evening cortisol levels (r = -0.21, p = 0.09) were negatively correlated with PSS scores. Conclusion: Maternal stress during pregnancy was not associated with birthweight. The inverse correlation between PSS scores and cortisol levels may indicate other mechanisms for maternal stress on child outcomes than the previous explanation of hypothalamic-pituitary-adrenal axis activity.
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| 9. |
- Ullemar, Vilhelmina
(författare)
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Transmitted and acquired determinants for childhood asthma : from genes to teens
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The interplay between genetic and environmental factors is central to childhood asthma and allergic disease. Transmitted and acquired risk factors collaborate to produce the phenotypic variation of a trait within the population. In this work, we have employed studies of twins to illustrate the relationship between twinship itself, early growth, and genetic and epigenetic factors with childhood asthma. Twins have been suggested to be a high risk group for asthma. Study I was a large population-based register study of twinship in itself as a risk factor for childhood asthma. Asthma diagnoses and medication use among Swedish twins and singletons born 1993-2001 and 2005-2009 were compared before and after controlling for birth weight and gestational age. In the younger group, twins were at higher risk of developing asthma before controlling for perinatal factors – afterwards, twins were at lower risk of asthma in both age groups. This suggests that important mechanisms for asthma are shared between twins and singletons. Low birth weight and rapid early growth have been shown to increase the risk of asthma. The aim of Study II was to describe the association between early growth and asthma in twins. Height and weight from 0 to 3 years of age were modelled in 2,874 twins. There was an association between later timing of maximum growth velocity and asthma both in terms of weight and height, although this relationship did not remain after controlling for birth weight or gestational age, which indicates that early postnatal growth may primarily be of interest as an extension of preceding foetal growth. There is significant comorbidity between asthma and other allergic diseases. In Study III, we studied the influence of genetic factors on childhood asthma, hay fever, atopic eczema and food allergy. Using twin models and data from 25,306 twins, we concluded that asthma and all of the other allergic phenotypes were highly influenced by additive genetic effects. A preselected set of high-risk genetic variants were primarily associated with asthma or both asthma and hay fever (rs3771180 in IL1RL1). Epigenetic factors have been suggested as a potential explanation for disease discordance within identical twin pairs. In Study IV, we analysed DNA methylation in whole blood of 708 twins with and without asthma using the Illumina 450k Beadchip. On the group level, 340 CpG sites were significantly associated with current asthma at 9-14 years of age, but these associations were not replicated within asthma-discordant pairs. Confounding by genetic factors or cell type composition in the samples seemed to be of importance, and should be considered as influences of potential importance in future epigenetic studies. In conclusion, the work described in this thesis has combined the unique qualities of twin studies with data from population-based registers, interviews, and clinical examinations. The influences of transmitted (genetic) and acquired (twinship, early growth, and epigenetics) on childhood asthma were evaluated. From this selection, the transmitted factors proved to be of most importance to childhood asthma.
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| 10. |
- Ullemar, Vilhelmina, et al.
(författare)
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Twins' risk of childhood asthma mediated by gestational age and birthweight
- 2016
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Ingår i: Clinical and Experimental Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0954-7894. ; 45:8, s. 1328-1336
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children born with low gestational age (GA) or low birth weight (BW) are at increased risk of asthma. Twins as compared to singletons are on average more likely to be born with lower GA and BW, and have been hypothesized to comprise a high risk population for asthma. Many previous studies have not accounted for potential confounders or mediators. Objective: To investigate the association between twinship and childhood asthma or early life wheeze and identify potential mediators, such as GA/BW. Methods: The study population consisted of two cohorts including all children born in Sweden from January 1st 1993 to June 1st 2001 (n=756,363 singletons, n=22,478 twins) and July 1st 2005 to December 31st 2009 (n=456,239 singletons, n=12,872 twins). Asthma was defined using validated register-based outcomes of diagnosis or medication. The data were analysed using logistic (older cohort) and Cox regression (younger cohort). Adjusted models incorporated potential confounding or mediating factors including gestational age and birth weight. Results: In the younger cohort, the crude hazard ratio (HR) of asthma medication after 1.5 years of age was 1.12 (95% CI 1.01-1.23), and fully adjusted HR 0.80, 95% CI 0.72-0.89. Crude HR of asthma diagnosis in the same age group was 1.14 (95% CI 0.99-1.30), fully adjusted 0.78 (0.68-0.98). Adjusted analyses in the older group yielded similar results. Conclusions: Twins were at significantly higher unadjusted risk of asthma or early life wheeze compared to singletons in the younger, but not in the older cohort. Associations attenuated following adjustment for GA/BW suggesting that GA/BW mediates the effect of twinship on asthma risk. After adjustments twins were at lower risk of asthma outcomes, possibly due to unmeasured confounding.
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