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- Fall, Tove, et al.
(author)
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The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis
- 2013
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474-
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Journal article (peer-reviewed)abstract
- Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
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| 2. |
- Khalife, Natasha, et al.
(author)
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Prenatal Glucocorticoid Treatment and Later Mental Health in Children and Adolescents
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. Art. no. e81394-
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Journal article (peer-reviewed)abstract
- Background: Animal studies demonstrate a clear link between prenatal exposure to glucocorticoids (GC) and altered offspring brain development. We aim to examine whether prenatal GC exposure programs long-term mental health in humans. Methods: Using propensity-score-matching, children prenatally exposed to synthetic glucocorticoids (sGC), n=37, and controls, n=185, were balanced on important confounders related to sGC treatment - gestational age and pre-pregnancy BMI. We also used mixed-effects modeling to analyse the entire cohort - matching each sGC case, n=37, to all possible controls, n=6079, on gestational age and sex. We obtained data from the Northern Finland Birth Cohort 1986 at four waves - pregnancy, birth, 8 and 16 years. Data on pregnancy and birth outcomes came from medical records. Mental health was assessed at 8 years by teachers with the Rutter B2 scale, and at 16 years by parents with the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale and adolescents by the Youth Self-Report (YSR) scale. Results: Prenatal sGC treatment was consistently associated with adverse mental health in childhood and adolescence, as shown by both the propensity-score method and mixed-effects model. Using the propensity-score-matched subsample, linear multiple regression showed prenatal sGC was significantly linked with general psychiatric disturbance (B=8.34 [95% CI: .23-16.45]) and inattention (B=.97 [95% CI:. 16-1.80]) at 8 years after control for relevant confounders. Similar findings were obtained at 16 years, but did not reach statistical significance. Mediation by birthweight/placental weight was not detected. Conclusions: This study is the first to prospectively investigate the long-term associations between prenatal exposure to sGC treatment and mental health in children and adolescents. We report an association between prenatal exposure to sGC and child mental health, supportive of the idea that sGC has a programming effect on the fetal brain.
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| 3. |
- Nordstrom, Tanja, et al.
(author)
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Comorbidity of disruptive behavioral disorders and attention-deficit hyperactivity disorder-Indicator of severity in problematic behavior?
- 2013
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In: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 67:4, s. 240-248
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Journal article (peer-reviewed)abstract
- Background: Disruptive behavioral disorders (DBD) and attention-deficit hyperactivity disorder (ADHD) are both characterized by certain patterns of misbehavior among adolescents. Aims: The aim of this study was to examine how the comorbidity of DBD and ADHD affects in misbehavior among adolescents. Methods: A total of 158 adolescents aged 16-18 years, from a subsample of the Northern Finland Birth Cohort 1986 (NFBC 1986), were interviewed with the Finnish translation of the semi-structured Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime (K-SADS-PL) in order to obtain DBD, including conduct disorder (CD) and oppositional defiant disorder (ODD), and ADHD diagnoses. The structure of the CD symptoms, obtained from the K-SADS-PL, was compared with the previously formed model about the development of the problematic behavior. The severity of the CD symptoms was compared with adolescents diagnosed with only DBD, only ADHD and with both DBD and ADHD. Also, the associations with other psychiatric disorders diagnosed at age 16 were evaluated. Results: The boys in the study sample were diagnosed with ADHD or with comorbid DBD and ADHD more often than girls. The severity of CD symptoms was statistically significantly associated with the comorbid DBD and ADHD group. The adolescents diagnosed with comorbid DBD and ADHD had an increased risk for anxiety disorders, depressive disorders and substance abuse disorders. Conclusions: The comorbidity of DBD and ADHD seems to indicate the severity of CD symptoms. Clinical implications: The comorbidity between DBD and ADHD should be considered in clinical practice because it could indicate more serious problematic behavior than pure disorders alone.
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