Biology subjects

Sallis, H.

Publications and source records attributed to Sallis, H..

4 recordsLinked to original sources

bioRxiv2019

Investigating causal pathways between liability to ADHD and substance use, and liability to substance use and ADHD risk, using Mendelian randomization.

BackgroundAttention-deficit hyperactivity disorder (ADHD) has consistently been associated with substance (ab)use, but the nature of this association is not fully understood. In view of preventive efforts, a vital question is whether there are causal effects, from ADHD to substance use and/or from substance use to ADHD. MethodsWe applied bidirectional Mendelian randomization using summary-level data from the largest available genome-wide association studies (GWASs) on ADHD, smoking (initiation, cigarettes/day, cessation, and a compound measure of lifetime smoking), alcohol use (drinks/week and alcohol use disorder), cannabis use (initiation and cannabis use disorder (CUD)) and coffee consumption (cups/day). Genetic variants robustly associated with the exposure were selected as instruments and then identified in the outcome GWAS. Effect estimates from individual genetic variants were combined with inverse-variance weighted regression and five sensitivity analyses were applied (weighted median, weighted mode, MR-Egger, generalized summary-data-based MR, and Steiger filtering). ResultsWe found strong evidence that liability to ADHD increases likelihood of smoking initiation and also cigarettes per day among smokers, decreases likelihood of smoking cessation, and increases likelihood of cannabis initiation and CUD. In the other direction, there was evidence that liability to smoking initiation and CUD increase ADHD risk. There was no clear evidence of causal effects between liability to ADHD and alcohol or caffeine consumption. ConclusionsWe find evidence for causal effects of liability to ADHD on smoking and cannabis use, and of liability to smoking and cannabis use on ADHD risk, indicating bidirectional pathways. Further work is needed to explore causal mechanisms.

genetics↗

bioRxiv2019

Smoking and the risk for bipolar disorder: causal evidence from a bidirectional Mendelian randomization study

ImportanceThere is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder. Research that investigates causality and the direction of the relationship between smoking and bipolar disorder has been lacking.\n\nObjectiveTo investigate the direction and causal nature of the relationship between smoking and bipolar disorder we conducted a bidirectional Mendelian randomization (MR) study.\n\nData sourcesPublicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e., a compound measure of heaviness, duration and cessation). We applied multiple analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger or Egger SIMEX, weighted median, weighted mode, and Steiger filtered analyses.\n\nResultsAcross different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW=1.46, 95% CI=1.28-1.66, P=1.44x10-8, lifetime smoking ORIVW=1.72, 95% CI=1.29-2.28, P=1.8x10-4). The MR analyses of the liability of bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking initiation betaIVW= -0.008, 95% CI= -0.026-0.009, P=0.35; P=0.94; smoking heaviness betaIVW=0.028, 95% CI= 0.003-0.053, P=2.9x10-2; smoking cessation ORIVW= 0.997, 95% CI= 0.981-1.014, P=0.74; lifetime smoking betaIVW= -0.001, 95%CI=-0.022-0.020, P=0.95).\n\nConclusionsThese findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to smoking increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.

neuroscience↗

bioRxiv2019

Specific domains of early parenting, their heritability and differential association with adolescent behavioural and emotional disorders and academic achievement

BackgroundVariations in parenting across large populations have rarely been described. It also remains unclear which specific domains of parenting are important for which specific offspring developmental outcomes. The study describes different domains of early parenting behaviours, their genetic heritability, and then determines the extent to which specific domains of parenting are associated with later offspring outcomes.\n\nMethodsParenting behaviours (birth to 3 years) were extracted from self-reported questionnaires administered to 12,358 mothers from the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children, and modelled as a latent factor using Confirmatory Factor Analysis. Genetic heritability and correlations between parenting factors were estimated using wide complex trait analysis. Offspring emotional, behavioural and academic outcomes were assessed at age 16 years using the self-reported Short Mood and Feelings Questionnaire, the Development and Well-Being Assessment, and grades achieved in national English Language examination.\n\nResultsThree parenting factors were derived: parental enjoyment, conflictual relationships and stimulation; all showed low genetic heritability. There was no evidence of associations between parenting factors and offspring depressed mood. Stimulation was associated with better English grades after controlling for maternal education (standardised {beta}=0.058, p=0.007), and enjoyment was negatively associated with English grades ({beta}=-0.082, p=0.002). Conflictual relationships were associated with higher risk of offspring behavioural disorders after controlling for behavioural problems at age 3 years ({beta}=0.227, p=0.007). Higher enjoyment reduced the association between conflict and behavioural problems (interaction term {beta}=0.113, p<0.001).\n\nConclusionsWe found evidence for predictive specificity of early parenting domains for offspring outcomes in adolescence. Early stimulation, unlike enjoyment, promoted later educational achievement. Conflictual relationships were associated with greater risk of behavioural problems, buffered by increased enjoyment. These findings hold implications for parenting interventions, guiding their focus according to specificity of parenting domains and their long-term outcomes in children.

epidemiology↗

bioRxiv2017

The molecular genetics of participation in the Avon Longitudinal Study of Parents and Children

BackgroundIt is often assumed that selection (including participation and dropout) does not represent an important source of bias in genetic studies. However, there is little evidence to date on the effect of genetic factors on participation.\n\nMethodsUsing data on mothers (N=7,486) and children (N=7,508) from the Avon Longitudinal Study of Parents and Children, we 1) examined the association of polygenic risk scores for a range of socio-demographic, lifestyle characteristics and health conditions related to continued participation, 2) investigated whether associations of polygenic scores with body mass index (BMI; derived from self-reported weight and height) and self-reported smoking differed in the largest sample with genetic data and a sub-sample who participated in a recent follow-up and 3) determined the proportion of variation in participation explained by common genetic variants using genome-wide data.\n\nResultsWe found evidence that polygenic scores for higher education, agreeableness and openness were associated with higher participation and polygenic scores for smoking initiation, higher BMI, neuroticism, schizophrenia, ADHD and depression were associated with lower participation. Associations between the polygenic score for education and self-reported smoking differed between the largest sample with genetic data (OR for ever smoking per SD increase in polygenic score:0.85, 95% CI:0.81,0.89) and sub-sample (OR:0.95, 95% CI:0.88,1.02). In genome-wide analysis, single nucleotide polymorphism based heritability explained 17-31% of variability in participation.\n\nConclusionsGenetic association studies, including Mendelian randomization, can be biased by selection, including loss to follow-up. Genetic risk for dropout should be considered in all analyses of studies with selective participation.

genetics↗