| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Brazel, David M., et al.
(författare)
-
Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use
- 2019
-
Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 85:11, s. 946-955
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.METHODS: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals.CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
|
|
| 25. |
- Brikell, Isabell, et al.
(författare)
-
Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder : A Nationwide Cohort Study
- 2018
-
Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 83:2, s. 173-180
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated; however, the underlying factors contributing to their co-occurrence remain unclear. A shared genetic liability has been proposed as one possible mechanism. Therefore, our goal in this study was to investigate the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence.METHODS: We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers and linked each individual to his or her biological relatives. We used logistic regression to estimate the association between epilepsy and ADHD within individual and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder covariance into genetic and environmental factors.RESULTS: Individuals with epilepsy had a statistically significant increased risk of ADHD (odds ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33-3.62). This risk increase extended to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75-1.96), children whose fathers had epilepsy (OR = 1.64, 95% CI = 1.54-1.74), full siblings (OR = 1.56, 95% CI = 1.46-1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14-1.43), paternal half siblings (OR = 1.10, 95% CI = 0.96-1.25), and cousins (OR = 1.15, 95% CI = 1.10-1.20). The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors (49%, nonshared environmental correlation = 0.36, 95% CI = 0.23-0.49). The contribution of shared environmental factors to the cross-disorder overlap was not statistically significant (11%, shared environmental correlation = 0.32, 95% CI = 20.16-0.79).CONCLUSIONS: This study demonstrates a strong and etiologically complex association between epilepsy and ADHD, with shared familial factors and risk factors unique to the individual contributing to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may share less genetic risk as compared with other neurodevelopmental disorders.
|
|
| 26. |
- Browning, Michael, et al.
(författare)
-
Lateral Prefrontal Cortex Mediates the Cognitive Modification of Attentional Bias
- 2010
-
Ingår i: Biological Psychiatry. - : ELSEVIER SCIENCE INC. - 0006-3223 .- 1873-2402. ; 67:10, s. 919-925
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A tendency to orient attention toward threatening stimuli may be involved in the etiology of anxiety disorders. In keeping with this, both psychological and pharmacological treatments of anxiety reduce this negative attentional bias. It has been hypothesized, but not proved, that psychological interventions may alter the function of prefrontal regions supervising the allocation of attentional resources. Methods: The current study examined the effects of a cognitive training regime on attention. Participants were randomly assigned to one of two training conditions: "attend-threat" training, which increases negative attentional bias, or "avoid-threat" training, which reduces it. The behavioral effects of training were assessed using a sample of 24 healthy participants. Functional magnetic resonance imaging data were collected in a further 29 healthy volunteers using a protocol that allowed the influence of both stimuli valence and attention to be discriminated. Results: Cognitive training induced the expected attentional biases in healthy volunteers. Further, the training altered lateral frontal activation to emotional stimuli, with these areas responding specifically to violations of the behavioral rules learned during training. Connectivity analysis confirmed that the identified lateral frontal regions were influencing attention as indexed by activity in visual association cortex. Conclusions: Our results indicate that frontal control over the processing of emotional stimuli may be tuned by psychological interventions in a manner predicted to regulate levels of anxiety. This directly supports the proposal that psychological interventions may influence attention via an effect on the prefrontal cortex.
|
|
| 27. |
- Browning, Michael, et al.
(författare)
-
Using Attentional Bias Modification as a Cognitive Vaccine Against Depression
- 2012
-
Ingår i: Biological Psychiatry. - : ELSEVIER SCIENCE INC. - 0006-3223 .- 1873-2402. ; 72:7, s. 572-579
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Negative attentional biases are thought to increase the risk of recurrence in depression, suggesting that reduction of such biases may be a plausible strategy in the secondary prevention of the illness. However, no previous study has tested whether reducing negative attentional bias causally affects risk factors for depressive recurrence. The current experimental medicine study reports the effects of a computerized attentional bias modification (ABM) procedure on intermediate measures of the risk of depressive recurrence (residual depressive symptoms and the cortisol awakening response) in patients with recurrent depression. Methods: Sixty-one patients with at least two previous episodes of depression who were currently in remission were randomized to receive either an active (positive) or placebo computer-based ABM regime. The ABM regime presented either pictures of faces or words. Residual depressive symptoms, measured using the Beck Depression Inventory and the cortisol awakening response were measured immediately before and after completion of the bias modification and then again after 4 weeks' follow-up. Results: Positive, face-based ABM reduced both measures of recurrence risk (Beck Depression Inventory and cortisol awakening response). This effect occurred during the month following completion of bias modification. Word-based modification did not influence the outcome measures. Conclusions: Positive face-based ABM was able to reduce intermediate measures of recurrence risk in previously depressed patients. These results suggest that ABM may provide a "cognitive vaccine" against depression and offer a useful strategy in the secondary prevention of the illness.
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
