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Tyrrell J.,University of Exeter | Huikari V.,Institute of Health science | Christie J.T.,King's College London | Cavadino A.,University College London | And 52 more authors.
Human Molecular Genetics | Year: 2012

Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P 5 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P 5 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: 24 to 14 g; P 5 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight. © The Author 2012. Published by Oxford University Press. All rights reserved.


Myklestad K.,Norwegian University of Science and Technology | Vatten L.J.,Norwegian University of Science and Technology | Salvesen K.T.,Norwegian University of Science and Technology | Davey Smith G.,Center for Causal Analyses in Translational Epidemiology iTE | Romundstad P.R.,Norwegian University of Science and Technology
Annals of Epidemiology | Year: 2011

Purpose: It has been suggested that paternal genes may contribute to the risk of maternal hypertensive disorders in pregnancy and that genes associated with cardiovascular disease could be involved in the etiology of maternal hypertensive disorders in pregnancy. If these genes are of fetal origin, one would expect that paternal cardiovascular risk factors are associated with the fathering of pregnancies in which the mothers experience hypertensive disorders. Thus, we have studied 14,130 offspring and parents in Norway (1967-1997) to assess whether the fathering of pregnancies complicated by hypertensive disorders in the mother is associated with paternal cardiovascular risk factors. Methods: In a population-based study of 14,130 family units, data on parental cardiovascular risk factors (blood pressure, body mass index, waist circumference, nonfasting serum lipids and glucose) collected in the Norwegian Hunt Study (1995-1997) were linked to pregnancy data from the Medical Birth Registry of Norway (1967-1997). Multiple linear regression methods were used, and all analyses were adjusted for lifestyle factors likely to be shared by the parents. Results: There was no association between hypertensive disorders in pregnancy and paternal cardiovascular risk factors. Conclusions: We found no evidence that the fathering of pregnancies complicated by hypertensive disorders in the mother is associated with an unfavorable paternal cardiovascular risk profile. © 2011 Elsevier Inc.


Myklestad K.,Norwegian University of Science and Technology | Vatten L.J.,Norwegian University of Science and Technology | Magnussen E.B.,Norwegian University of Science and Technology | Salvesen K.S.,Norwegian University of Science and Technology | And 2 more authors.
American Journal of Epidemiology | Year: 2012

Low birth weight is associated with increased risk of cardiovascular disease and type 2 diabetes in later life. The fetal insulin hypothesis suggests that shared genetic factors partly explain this association. If fetal genes predispose to both low birth weight and cardiovascular disease in adulthood, fathers of offspring with low birth weight should display an unfavorable profile of cardiovascular risk factors. To study this, the authors linked data on more than 14,000 parents, collected from the second Health Study of Nord Trøndelag County, Norway (HUNT 2, 1995-1997), to offspring data from the Norwegian Medical Birth Registry (1967-2005). Linear regression was used to study associations of offspring birth weight for gestational age with the parents' body mass index, waist circumference, blood pressure, glucose, and serum lipids. All analyses were adjusted for shared environment by means of the socioeconomic measures, lifestyle, and cardiovascular risk factors of the partner. The authors found that low offspring birth weight for gestational age was associated with increased paternal blood pressure, body mass index, waist circumference, and unfavorable levels of glucose and lipids. For mothers, associations similar to those for fathers were found for blood pressure, whereas associations in the opposite direction were found for glucose, lipids, and body mass index. The paternal findings strengthen the genetic hypothesis. © 2012 The Author.

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