Biology subjects

Treur, J.

Publications and source records attributed to Treur, J..

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↗

bioRxiv2017

Causal Associations Between Body Mass Index and Mental Health: A Mendelian Randomization Study

BackgroundBody Mass Index (BMI) is negatively correlated with subjective well-being and positively correlated with depressive symptoms. Whether these associations reflect causal effects or confounding is unclear.\n\nMethodsWe examined causal effects between BMI and subjective well-being/depressive symptoms with bi-directional, two-sample Mendelian randomization using summary-level data from large genome-wide association studies. Genetic variants robustly related to the exposure variable acted as instrumental variable (two thresholds were used; p<5e-08 and p<1e-05). These instruments were then associated with the outcome variable. Pleiotropy was corrected for by two sensitivity analyses.\n\nResultsSubstantial evidence was found for a causal effect of BMI on mental health, such that a higher BMI decreased subjective well-being and increased depressive symptoms. No consistent evidence was found for causality in the other direction.\n\nConclusionsThis study provides support for a higher BMI causing poorer mental health. Further research should corroborate these findings and consider non-linear effects and sex differences.

genetics↗

bioRxiv2017

Cigarette smoking increases coffee consumption: findings from a Mendelian randomisation analysis

BackgroundSmokers tend to consume more coffee than non-smokers and there is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases the metabolism of caffeine, so this association may represent a causal effect of smoking on caffeine intake.\n\nMethodsWe performed a Mendelian randomisation analysis in 114,029 individuals from the UK Biobank, 56,664 from the Norwegian HUNT study and 78,650 from the Copenhagen General Population Study. We used a genetic variant in the CHRNA5 nicotinic receptor (rs16969968) as a proxy for smoking heaviness. Coffee and tea consumption were self-reported. Analyses were conducted using linear regression and meta-analysed across studies.\n\nResultsEach additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI:0.03,0.17). There was weak evidence for an increase in tea consumption per additional cigarette smoked per day (0.04 cups per day, 95% CI:-0.002,0.07). There was strong evidence that each additional copy of the minor allele of rs16969968 (which increases daily cigarette consumption) in current smokers was associated with higher coffee consumption (0.15 cups per day, 95% CI:0.11,0.20), but only weak evidence for an association with tea consumption (0.04 cups per day, 95% CI:- 0.01,0.09). There was no clear evidence that rs16969968 was associated with coffee or tea consumption in never or former smokers.\n\nConclusionThese findings suggest that higher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but may also reflect behavioural links between smoking and coffee.

genetics↗