Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Predictors of early adulthood insomnia following exposure to a single mass violence attack during adolescence: 7–13 year follow-up from the Utøya and HUNT studies

ABSTRACTBackground: The long-term impact of mass violence attacks is practically unknown, especially in children and adolescents. In a previous study, we found that 8.5 years after a terror attack targeting mainly adolescents, nearly half of the survivors met diagnostic criteria for insomnia.Objectives: The aims of this study were to investigate: (1) whether exposure to a single mass violence event during adolescence increases the risk of insomnia almost a decade later above that expected for a non-exposed population; and (2) whether prior interpersonal violence exposure and early post-traumatic reactions predict later insomnia.Method: Participants were survivors of the 2011 Utøya Island terrorist attack (n = 279) and controls from the HUNT Norwegian general population study (n = 35,664). Early adulthood insomnia was assessed using four items from the Karolinska Sleep Questionnaire 8.5 years after the attack. Participants who had also completed earlier data collection waves for both studies (n = 116 and 2382, respectively) were included in logistic regression models testing the associations between predictors during adolescence and later insomnia.Results: Nearly a decade after the Utøya attack, 38.4% (n = 56) of the survivors reported symptoms of insomnia indicative of probable insomnia compared to 20.5% (n = 5771) of controls. Terror exposure during adolescence was a significant predictor of later insomnia [odds ratio (OR) = 3.18, 95% confidence interval (CI) = 2.05–4.87, p < .001]. Early post-trauma symptoms of anxiety and depression (OR = 1.34, 95% CI = 1.02–1.76, p = .033) and weekly headaches (OR = 1.64, 95% CI = 1.08–2.47, p = .018) were also significant predictors while controlling for background factors and other predictors.Conclusion: Long-term assessment and treatment are needed for survivors of mass violence to improve resilience and recovery

The effect of foetal growth restriction on the development of migraine and tension-type headache in adulthood. The HUNT Study.

There is little knowledge about how factors early in life affect the development of migraine and tension-type headache. We aimed to examine whether growth restriction in utero is associated with development of migraine and frequent tension-type headache in adults.The population-based Nord-Trøndelag Health Study (HUNT 3) contained a validated headache questionnaire, which differentiated between migraine and tension-type headache. These data were linked to information on weight and gestational age at birth from the Norwegian Medical Birth Registry. In total 4557 females and 2789 males, aged 19-41 years, were included in this registry-based study. Participants were categorized as appropriate for gestational age (AGA, 10th-90th percentile), small for gestational age (SGA, 3rd-10th percentile) or very small for gestational age (VSGA, < 3rd percentile). Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for migraine and tension-type headache, with exposure being growth restriction at birth.The effect of growth restriction on migraine was modified by sex, with a significant association in males (p<0.001), but not in females (p = 0.20). In particular, males born VSGA were at increased risk of developing migraine (OR 2.73, 95% CI 1.63-4.58, p<0.001), with an intermediate risk among those born SGA (OR 1.50, 95% CI 0.96-2.35, p = 0.08) compared to those born AGA. There was no significant association between growth restriction and frequent TTH (p = 0.051).Growth restriction was associated with increased risk of migraine in adulthood among males, but not among females. This suggests that migraine might, in part, be influenced by early life events, and that males seem to be particularly vulnerable

The Effect of Weight for Gestational Age on Development of Migraine.

<p>The Effect of Weight for Gestational Age on Development of Migraine.</p

Estimated Probabilities of Migraine (%) by Weight/Gestational Age and Sex.

<p>AGA: Appropriate for gestational age (weight by gestational age 10^th-90^th percentile); SGA: Small for gestational age (3^rd-10^th percentile); VSGA: Very small for gestational age (<3^rd percentile); LGA: Large for gestational age (90^th-100^th percentile).</p

Characteristics of the Participants.

<p>Characteristics of the Participants.</p