| 1. |
- 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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| 2. |
- Almqvist, Catarina, et al.
(författare)
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The impact of birth mode of delivery on childhood asthma and allergic diseases : a sibling study
- 2012
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Ingår i: Clinical and experimental allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1365-2222 .- 0954-7894.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Caesarean section (CS) has been reported to increase the risk of asthma in offspring. This may be due to that infants delivered by CS are unexposed to vaginal flora, according to the ‘hygiene hypothesis’. Objective: Our aim was to investigate if CS increases risk of childhood asthma, and if the risk increase remains after adjustment for familial confounding using sibling design. Methods: A register-based cohort study with 87 500 Swedish sibling pairs was undertaken. Asthma outcome variables were collected from national health registers as diagnosis or asthma medication (ICD-10 J45-J46; ATC code R03) during the 10th or 13th year of life (year of follow-up). Mode of delivery and confounders were retrieved from the Medical Birth Register. The data were analysed both as a cohort and with sibling control analysis which adjusts for unmeasured familial confounding. Results: In the cohort analyses, there was an increased risk of asthma medication and asthma diagnosis during year of follow-up in children born with CS (adjusted ORs, 95% CI 1.13, 1.04–1.24 and 1.10, 1.03–1.18 respectively). When separating between emergency and elective CS the effect on asthma medication remained for emergency CS, but not for elective CS, while both groups had significant effects on asthma diagnosis compared with vaginal delivery. In sibling control analyses, the effect of elective CS on asthma disappeared, while similar but non-significant ORs of medication were obtained for emergency CS. Conclusions and Clinical Relevance: An increased risk of asthma medication in the group born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora. A more probable explanation should be sought in the indications for emergency CS.
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| 3. |
- Brew, Bronwyn K., et al.
(författare)
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Longitudinal depression or anxiety in mothers and offspring asthma : a Swedish population-based study
- 2018
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 47:1, s. 166-174
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous research has found that maternal stress during pregnancy increases the risk of offspring asthma. However, whether this association is consistent with a causal interpretation has never been tested. The objective is to determine whether there is a critical exposure period for maternal depression or anxiety on offspring asthma or whether cumulative exposure is most important, and to investigate evidence of confounding.Methods: The study population included all children born in Sweden from July 2006 to December 2009 (n = 360 526). Information about childhood asthma, maternal depression or anxiety (diagnosis or medication) and covariates was obtained from the Swedish national health registers. The associations between exposure periods (pre-conception, pregnancy, postnatal or current) and childhood asthma were estimated using structured life course approach hypothesis testing. Paternal and cousin analyses were used to test for evidence of confounding from shared genes and environment.Results: For childhood asthma, cumulative exposure best described the effect of exposure to maternal depression or anxiety up to a maximum of any two exposure periods [adjusted odds ratio 1.44, 95% confidence interval (CI) 1.38, 1.52]. The hypotheses of a critical period were not supported. The paternal and cousin analyses indicated minimal influence from familial confounding.Conclusions: These findings support an association between cumulative exposure to maternal depression or anxiety and asthma development in offspring. This association is unique for maternal depression or anxiety and not due to familial confounding. The clinical implication is that effective psychological management of women with chronic distress may reduce offspring asthma risk.
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| 4. |
- Fang, Fang, et al.
(författare)
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Maternal bereavement and childhood asthma-analyses in two large samples of Swedish children
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11, s. e27202-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prenatal factors such as prenatal psychological stress might influence the development of childhood asthma. METHODOLOGY AND PRINCIPAL FINDINGS: We assessed the association between maternal bereavement shortly before and during pregnancy, as a proxy for prenatal stress, and the risk of childhood asthma in the offspring, based on two samples of children 1-4 (n = 426 334) and 7-12 (n = 493 813) years assembled from the Swedish Medical Birth Register. Exposure was maternal bereavement of a close relative from one year before pregnancy to child birth. Asthma event was defined by a hospital contact for asthma or at least two dispenses of inhaled corticosteroids or montelukast. In the younger sample we calculated hazards ratios (HRs) of a first-ever asthma event using Cox models and in the older sample odds ratio (ORs) of an asthma attack during 12 months using logistic regression. Compared to unexposed boys, exposed boys seemed to have a weakly higher risk of first-ever asthma event at 1-4 years (HR: 1.09; 95% confidence interval [CI]: 0.98, 1.22) as well as an asthma attack during 12 months at 7-12 years (OR: 1.10; 95% CI: 0.96, 1.24). No association was suggested for girls. Boys exposed during the second trimester had a significantly higher risk of asthma event at 1-4 years (HR: 1.55; 95% CI: 1.19, 2.02) and asthma attack at 7-12 years if the bereavement was an older child (OR: 1.58; 95% CI: 1.11, 2.25). The associations tended to be stronger if the bereavement was due to a traumatic death compared to natural death, but the difference was not statistically significant. CONCLUSIONS/SIGNIFICANCE: Our results showed some evidence for a positive association between prenatal stress and childhood asthma among boys but not girls.
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| 5. |
- Gong, Tong, et al.
(författare)
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Exposure to air pollution from traffic and neurodevelopmental disorders in Swedish twins.
- 2014
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Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - Stockholm : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 17:6, s. 553-62
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have reported associations between air pollution exposure and neurodevelopmental disorders in children, but the role of pre- and postnatal exposure has not been elucidated.
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| 6. |
- Gong, Tong, et al.
(författare)
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Parental asthma and risk of autism spectrum disorder in offspring : a population and family based case-control study
- 2019
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Ingår i: Clinical and Experimental Allergy. - : Blackwell Science Ltd.. - 0954-7894 .- 1365-2222. ; 49:6, s. 883-891
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between parental asthma and prenatal exposure to asthma medications with offspring autism spectrum disorder (ASD) have been reported. However, the associations might be confounded by unmeasured (genetic and shared environmental) familial factors.OBJECTIVE: We investigated the association between (a) maternal/paternal asthma and offspring ASD, and (b) prenatal exposures to β2-agonists, other asthma medications and offspring ASD using cases and controls selected from the population as well as biological relatives with different degrees of relatedness.METHODS: We included all children (N=1,579,263) born in Sweden 1992-2007. A nested case-control design was used to compare 22,894 ASD cases identified from the National Patient Register to (i) 228,940 age-, county- and sex-matched controls randomly selected from the population, (ii) their eligible full-siblings (n=1,267), (iii) half-siblings (n=1,323), (iv) full-cousins (n=11,477), and (v) half-cousins (n=3,337). Conditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for ASD in children differentially exposed to parental asthma or prenatal asthma medications.RESULTS: Maternal asthma was associated with increased risk of offspring ASD (OR 1.43, 95% CI 1.38-1.49); there was a weaker association for paternal asthma (OR 1.17, 95% CI 1.11-1.23). The risk of offspring ASD in mothers with asthma showed similar estimates when adjusting for shared familial factors among paternal half-siblings (OR 1.20, 95% CI 0.80-1.81), full-cousins (OR 1.28, 95% CI 1.16-1.41), and half-cousins (OR 1.30, 95% CI 1.10-1.54), albeit with wider confidence intervals. Prenatal exposure to asthma medications among subjects whose mothers had asthma was not associated with subsequent ASD.CONCLUSIONS AND CLINICAL RELEVANCE: In this large observational study, parental asthma was associated with slightly elevated risk of ASD in offspring. More specifically, the increased risk by maternal asthma did not seem to be confounded by familial factors. There was no evidence of an association between asthma medications during pregnancy and offspring ASD.
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| 7. |
- Halldner, Linda, et al.
(författare)
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Relative immaturity and ADHD : findings from nationwide registers, parent- and self-reports
- 2014
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Ingår i: Journal of Child Psychology and Psychiatry. - Stockholm : Wiley-Blackwell. - 0021-9630 .- 1469-7610. ; 55:8, s. 897-904
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We addressed if immaturity relative to peers reflected in birth month increases the likelihood of ADHD diagnosis and treatment.METHODS: We linked nationwide Patient and Prescribed Drug Registers and used prospective cohort and nested case-control designs to study 6-69 year-old individuals in Sweden from July 2005 to December 2009 (Cohort 1). Cohort 1 included 56,263 individuals diagnosed with ADHD or ever used prescribed ADHD-specific medication. Complementary population-representative cohorts provided DSM-IV ADHD symptom ratings; parent-reported for 10,760 9-year-old twins born 1995-2000 from the CATSS study (Cohort 2) and self-reported for 6,970 adult twins age 20-47 years born 1959-1970 from the STAGE study (Cohort 3). We calculated odds ratios (OR:s) for ADHD across age for individuals born in November/December compared to January/February (Cohort 1). ADHD symptoms in Cohorts 2 and 3 were studied as a function of calendar birth month.RESULTS: ADHD diagnoses and medication treatment were both significantly more common in individuals born in November/December versus January/February; peaking at ages 6 (OR: 1.8; 95% CI: 1.5-2.2) and 7 years (OR: 1.6; 95% CI: 1.3-1.8) in the Patient and Prescribed Drug Registers, respectively. We found no corresponding differences in parent- or self-reported ADHD symptoms by calendar birth month.CONCLUSION: Relative immaturity compared to class mates might contribute to ADHD diagnosis and pharmacotherapy despite absence of parallel findings in reported ADHD symptom loads by relative immaturity. Increased clinical awareness of this phenomenon may be warranted to decrease risk for imprecise diagnostics and treatment. We speculate that flexibility regarding age at school start according to individual maturity could reduce developmentally inappropriate demands on children and improve the precision of ADHD diagnostic practice and pharmacological treatment.
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| 8. |
- Havland, Ida, et al.
(författare)
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The observed association between maternal anxiety and adolescent asthma : children of twin design suggest familial effects
- 2013
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Ingår i: PLoS One. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1932-6203. ; 42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies indicate that maternal anxiety is associated with asthma in the adolescent child, but mechanisms are unclear. OBJECTIVE: To investigate the association between maternal anxiety and maternal, self- and register-based report of asthma in the adolescent child, and whether the association remains after control of familial confounding (shared environmental and genetic factors). METHOD: From the Twin and Offspring Study of Sweden, 1691 mothers (1058 twins) and their adolescent child were included. The association between maternal self-reported anxiety (Beck Anxiety Inventory (BAI) and Karolinska Scales of Personality (KSP) somatic or psychic anxiety) and asthma based on subjective (maternal or child report) or objective (register-based diagnosis and medication) measures were analysed using logistic regression. The children-of-twins design was used to explore whether genes or environment contribute to the association. RESULTS: Maternal BAI anxiety (OR 2.02, CI 1.15-3.55) was significantly associated with adolescent asthma reported by the mother. Maternal KSP somatic anxiety (OR 1.74, CI 1.04-2.91) and psychic anxiety (OR 1.74, CI 1.05-2.86) was significantly associated with breathlessness reported by the adolescent child. In contrast, maternal anxiety was not associated with increased risk for the register-based outcomes of asthma diagnosis or medication. The results remained also after adjusting for covariates and the children-of-twins analyses which indicate that the association was due to familial confounding. CONCLUSIONS: We found some associations between maternal anxiety and subjectively reported offspring asthma or breathlessness which may be due to familial effects. A likely candidate for explaining this familial confounding is heritable personality traits associated with both anxiety and subjective measures of asthma.
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| 9. |
- Johansson, Viktoria, et al.
(författare)
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Multiple sclerosis and psychiatric disorders : comorbidity and sibling risk in a nationwide Swedish cohort
- 2014
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Ingår i: Multiple Sclerosis Journal. - Stockholm : Sage Publications. - 1352-4585 .- 1477-0970. ; 20:14, s. 1881-1891
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Psychiatric disorders are known to be prevalent in multiple sclerosis (MS).OBJECTIVE: The objective of this paper is to study comorbidity between MS and bipolar disorder, schizophrenia and depression in a nationwide cohort and to determine whether shared genetic liability underlies the putative association.METHODS: We identified ICD-diagnosed patients with MS (n = 16,467), bipolar disorder (n = 30,761), schizophrenia (n = 22,781) and depression (n = 172,479) in the Swedish National Patient Register and identified their siblings in the Multi-Generation Register. The risk of MS was compared in psychiatric patients and in matched unexposed individuals. Shared familial risk between MS and psychiatric disorders was estimated by sibling comparison.RESULTS: The risk of MS was increased in patients with bipolar disorder (hazard ratio (HR) 1.8, 95% confidence interval (CI) 1.6-2.2, p < 0.0001) and depression (HR 1.9, 95% CI 1.7-2.0, p < 0.0001). MS risk in schizophrenia was decreased (HR 0.6, 95% CI 0.4-0.9, p = 0.005). The association between having a sibling with a psychiatric disorder and developing MS was not significant.CONCLUSION: We found a strong positive association between MS and bipolar disorder and depression that could not be explained by genetic liability. The unexpected negative association between MS and schizophrenia might be spurious or indicate possible protective mechanisms that warrant further exploration.
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| 10. |
- Rejnö, Gustaf, et al.
(författare)
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Adverse Pregnancy Outcomes in Asthmatic Women : A Population-Based Family Design Study
- 2018
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 2213-2198 .- 2213-2201. ; 6:3, s. 916-922.e6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Asthma is associated with several adverse pregnancy and perinatal outcomes. Familial factors may confound these associations.OBJECTIVE: To examine the role of measured and unmeasured confounding by conducting a study that compared differentially exposed cousins and siblings from the same families.METHODS: We retrieved data on adverse pregnancy outcomes, prescribed drugs, and physician-diagnosed asthma from nationwide registers for all women in Sweden with singleton births between 2001 and 2013. Logistic and linear regression estimated the association between maternal asthma and several outcomes in the whole population and within differently exposed pregnant relatives.RESULTS: In total, 1,075,153 eligible pregnancies were included and 10.1% of the study population had asthma. We identified 475,200 cousin and 341,205 sister pregnancies. Women with asthma had increased risks for preeclampsia (adjusted odds ratio [aOR], 1.17; 95% CI, 1.13-1.21), emergency cesarean section (aOR, 1.24; 95% CI, 1.22-1.27), and having a child small for gestational age (aOR, 1.18; 95% CI, 1.12-1.23). In the conditional regression analyses, after adjustment for familial factors, the associations remained: preeclampsia in cousins (aOR, 1.16; 95% CI, 1.07-1.25) and siblings (aOR, 1.23; 95% CI, 1.08-1.38), emergency cesarean section in cousins (aOR, 1.28) and siblings (aOR, 1.21), and small for gestational age in cousins (aOR, 1.17) and siblings (aOR, 1.13).CONCLUSIONS: Factors shared by siblings and cousins do not seem to explain the observed association between maternal asthma and adverse pregnancy outcomes. This implies that targeting the asthma disease will continue to be important in reducing risks for adverse outcomes in pregnancy.
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