| 11. |
- Khalife, Natasha, et al.
(författare)
-
Childhood Attention-Deficit/Hyperactivity Disorder Symptoms Are Risk Factors for Obesity and Physical Inactivity in Adolescence
- 2014
-
Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 53:4, s. 425-436
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To prospectively investigate the association and directionality between attention-deficit/hyperactivity disorder (ADHD) symptoms and obesity from childhood to adolescence in the general population. We examined whether obesogenic behaviors, namely, physical inactivity and binge eating, underlie the potential ADHD symptom obesity association. We explored whether childhood conduct disorder (CD) symptoms are related to adolescent obesity/physical inactivity. Method: At 7 to 8 years (n = 8,106), teachers reported ADHD and CD symptoms, and parents reported body mass index (BMI) and physically active play. At 16 years (n = 6,934), parents reported ADHD symptoms; adolescents reported physical activity (transformed to metabolic equivalent of task [MET] hours per week) and binge eating; BMI and waist hip ratio (WHR) were measured via clinical examination. Obesity was defined using the International Obesity Task Force (IOTF) cut-offs for BMI and the 95th percentile cut-off for WHR. Results: Childhood ADHD symptoms significantly predicted adolescent obesity, rather than the opposite. Inattention-hyperactivity symptoms at 8 years were associated with indices of obesity at 16 years (obese BMI: odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.10-3.33; 95th percentile WHR: OR = 1.71, 95% CI = 1.05-2.78), adjusted for gender, baseline BMI, physical activity, family structure change, and maternal education. Child CD symptoms associated with indices of adolescent obesity. Reduced physically active play in childhood predicted adolescent inattention (OR = 1.61,95% CI = 1.16-2.24). Childhood ADHD and CD symptoms were linked with physical inactivity in adolescence (inattention-hyperactivity; OR = 1.60, 95% CI = 1.20-2.13), but not binge eating. Physical inactivity mediated the associations. Conclusions: Children with ADHD or CD symptoms are at increased risk for becoming obese and physically inactive adolescents. Physical activity may be beneficial for both behavior problems and obesity.
|
|
| 12. |
- Lango Allen, Hana, et al.
(författare)
-
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
-
Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
|
|
| 13. |
- Lappalainen, Raimo, et al.
(författare)
-
The effectiveness and applicability of different lifestyle interventions for enhancing wellbeing : the study design for a randomized controlled trial for persons with metabolic syndrome risk factors and psychological distress.
- 2014
-
Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity and stress are among the most common lifestyle-related health problems. Most of the current disease prevention and management models are not satisfactorily cost-effective and hardly reach those who need them the most. Therefore, novel evidence-based controlled interventions are necessary to evaluate models for prevention and treatment based on self-management. This randomized controlled trial examines the effectiveness, applicability, and acceptability of different lifestyle interventions with individuals having symptoms of metabolic syndrome and psychological distress. The offered interventions are based on cognitive behavioral approaches, and are designed for enhancing general well-being and supporting personalized lifestyle changes.METHODS/DESIGN: 339 obese individuals reporting stress symptoms were recruited and randomized to either (1) a minimal contact web-guided Cognitive Behavioral Therapy-based (CBT) intervention including an approach of health assessment and coaching methods, (2) a mobile-guided intervention comprising of mindfulness, acceptance and value-based exercises, (3) a face-to-face group intervention using mindfulness, acceptance and value-based approach, or (4) a control group. The participants were measured three times during the study (pre = week 0, post = week 10, and follow-up = week 36). Psychological well-being, lifestyles and habits, eating behaviors, and user experiences were measured using online surveys. Laboratory measurements for physical well-being and general health were performed including e.g. liver function, thyroid glands, kidney function, blood lipids and glucose levels and body composition analysis. In addition, a 3-day ambulatory heart rate and 7-day movement data were collected for analyzing stress, recovery, physical activity, and sleep patterns. Food intake data were collected with a 48 -hour diet recall interview via telephone. Differences in the effects of the interventions would be examined using multiple-group modeling techniques, and effect-size calculations.DISCUSSION: This study will provide additional knowledge about the effects of three low intensity interventions for improving general well-being among individuals with obesity and stress symptoms. The study will show effects of two technology guided self-help interventions as well as effect of an acceptance and value-based brief group intervention. Those who might benefit from the aforesaid interventions will increase knowledge base to better understand what mechanisms facilitate effects of the interventions.TRIAL REGISTRATION: Current Clinical Trials NCT01738256, Registered 17 August, 2012.
|
|
| 14. |
- Lindgren, Cecilia M, et al.
(författare)
-
Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
-
Tidskriftsartikel (refereegranskat)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
|
|
| 15. |
- Patel, Swatee P., et al.
(författare)
-
Associations between pre-pregnancy obesity and asthma symptoms in adolescents
- 2012
-
Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 66:9, s. 809-814
-
Tidskriftsartikel (refereegranskat)abstract
- Background The high prevalence of children's asthma symptoms, worldwide, is unexplained. We examined the relation between maternal pre-pregnancy weight and body mass index (BMI), and asthma symptoms in adolescents.Methods Data from 6945 adolescents born within the Northern Finland Birth Cohort 1986 were used. Prospective antenatal and birth outcome data, including maternal pre-pregnancy weight and BMI, and asthma symptoms in adolescent offspring at age 15-16 years, were employed. Logistic regression analyses were performed to examine the associations between relevant prenatal factors and asthma symptoms during adolescence.Results Current wheeze (within the past year) was reported by 10.6% of adolescents, and physician-diagnosed asthma by 6.0%. High maternal pre-pregnancy BMI was a significant predictor of wheeze in the adolescents (increase per kilogram per square metre unit; 2.7%, 95% CI 0.9 to 4.4 for ever wheeze; 3.5%, 95% CI 1.3 to 5.8 for current wheeze), and adjusting for potential confounders further increased the risk (2.8%, 95% CI 0.5 to 5.1; 4.7%, 95% CI 1.9 to 7.7, respectively). High maternal pre-pregnancy weight, in the top tertile, also significantly increased the odds of current wheeze in the adolescent by 20% (95% CI 4 to 39), and adjusting for potential confounders further increased the risk (OR=1.52, 95% CI 1.19 to 1.95). Results were similar for current asthma. Furthermore, these significant associations were observed only among adolescents without parental history of atopy but not among those with parental history of atopy.Conclusions The association demonstrated here between maternal pre-pregnancy overweight and obesity, and asthma symptoms in adolescents suggests that increase in asthma may be partly related to the rapid rise in obesity in recent years.
|
|
| 16. |
- Pillas, Demetris, et al.
(författare)
-
Infant locomotive development and its association with adult blood pressure.
- 2014
-
Ingår i: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 0340-6199 .- 1432-1076. ; 173:10, s. 1309-17
-
Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Evidence from animal models suggests that locomotion and blood pressure share common neurophysiological regulatory systems. As a result of this common regulation, we hypothesized that the development of locomotion in human infants would be associated with blood pressure levels in adulthood. The study sample comprised 4,347 individuals with measures of locomotive and non-locomotive neuromotor development in infancy and adult blood pressure levels within a longitudinal birth cohort study, the Northern Finland Birth Cohort 1966. Later development in all three stages of locomotive development during infancy was associated with higher systolic and diastolic blood pressure levels at age 31. For age of walking without support, 0.34 (95 % CI 0.07 to 0.60)-mm Hg higher SBP and 0.38 (95 % CI 0.15 to 0.62)-mm Hg higher DBP were estimated for each month of later achievement (P = 0.012 for SBP; P = 0.001 for DBP). No association was identified for non-locomotive neuromotor development.CONCLUSION: These results highlight the positive sequelae of advanced locomotive development during infancy, suggesting that the common regulatory systems between locomotion and blood pressure may influence the development of raised blood pressure over time.
|
|
| 17. |
- Ried, Janina S., et al.
(författare)
-
A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
|
|
| 18. |
- Rung, Johan, et al.
(författare)
-
Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 89-1110
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified common variants that only partially explain the genetic risk for type 2 diabetes (T2D). Using genome-wide association data from 1,376 French individuals, we identified 16,360 SNPs nominally associated with T2D and studied these SNPs in an independent sample of 4,977 French individuals. We then selected the 28 best hits for replication in 7,698 Danish subjects and identified 4 SNPs showing strong association with T2D, one of which (rs2943641, P = 9.3 x 10(-12), OR = 1.19) was located adjacent to the insulin receptor substrate 1 gene (IRS1). Unlike previously reported T2D risk loci, which predominantly associate with impaired beta cell function, the C allele of rs2943641 was associated with insulin resistance and hyperinsulinemia in 14,358 French, Danish and Finnish participants from population-based cohorts; this allele was also associated with reduced basal levels of IRS1 protein and decreased insulin induction of IRS1-associated phosphatidylinositol-3-OH kinase activity in human skeletal muscle biopsies.
|
|
| 19. |
- Schumann, Gunter, et al.
(författare)
-
Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption
- 2011
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:17, s. 7119-7124
-
Tidskriftsartikel (refereegranskat)abstract
- Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of similar to 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Downregulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.
|
|
| 20. |
- Schumann, Gunter, et al.
(författare)
-
KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference
- 2016
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377
-
Tidskriftsartikel (refereegranskat)abstract
- Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
|
|
