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1.  Effects of maternal smoking during pregnancy on offspring blood pressure in late adolescence 
Journal of hypertension  2012;30(4):693-699.
Objectives
Previous studies suggest that maternal smoking during pregnancy is associated with elevated offspring blood pressure during childhood. We aimed to investigate whether this association remained in late adolescence and, if so, whether it could be attributed to an intrauterine effect or to familial confounding.
Methods
We used a national cohort of 87 223 young Swedish men born between 1983 and 1988 with information on both maternal smoking during pregnancy and blood pressure at military conscription. The cohort included 780 full brothers discordant for maternal smoking. Generalized estimation equations were used to estimate regression coefficients (b) with 95% confidence intervals (95% CIs).
Results
We found a small but significant increase in both SBP and DBP for young men whose mothers had been daily smokers during pregnancy compared with sons of nonsmoking mothers: 0.26 (95% CI 0.09 to 0.44) and 0.45mmHg (95% CI 0.31 to 0.59) for SBP and DBP, respectively. In a within-sibling analysis comparing full brothers discordant for maternal smoking exposure, point estimates were similar but not statistically significant: 0.85 (95% CI _0.19 to 1.90) for DBP and 0.81 (_0.56 to 2.19) for SBP.
Conclusion
Maternal smoking during pregnancy is associated with a small but statistically significant increase in offspring blood pressure in late adolescence. Because the association does not appear to be explained by familial confounding, our results support an intrauterine effect of prenatal smoking exposure on blood pressure in late adolescence.
doi:10.1097/HJH.0b013e32835168f4
PMCID: PMC3664185  PMID: 22388229
adolescent; blood pressure; maternal smoking; prenatal exposure delayed effects; siblings
2.  A quasi-experimental study of maternal smoking during pregnancy and offspring academic achievement 
Child development  2010;81(1):80-100.
Maternal smoking during pregnancy (SDP) is associated with lower academic achievement in offspring. The current study, which was based on all births in Sweden from 1983 through 1991, explored the possible causal processes underlying the association between SDP and offspring school grades and a standardized assessment of mathematic proficiency at age 15. The analyses compared relatives who varied in their exposure to SDP and who varied in their genetic relatedness. Although SDP was statistically associated with academic achievement when comparing unrelated individuals, the results suggest that SDP does not cause poorer academic performance, as full siblings differentially exposed to SDP did not differ in their academic scores. The pattern of results suggests that genetic factors shared by parents and their offspring explain significant variance in why offspring opposed to SDP have lower levels of academic achievement. Nevertheless, SDP impacts pregnancy-related outcomes. Reducing SDP, therefore, remains a major public health issue.
doi:10.1111/j.1467-8624.2009.01382.x
PMCID: PMC3656473  PMID: 20331655
3.  Maternal Smoking During Pregnancy and Intellectual Performance in Young Adult Swedish Male Offspring 
SUMMARY
Smoking during pregnancy has been linked to an increased risk of several adverse birth outcomes. Associations with deficits in cognitive development have also been suggested. It is unclear if these associations are due to genetic and/or environmental confounding. In a population-based Swedish cohort study on 205 777 singleton males born to Nordic mothers between 1983 and 1988, we examined the association between maternal smoking during pregnancy and the risk of poor intellectual performance in young adult male offspring. In the cohort analyses, the risk of poor intellectual performance was increased in sons of smoking mothers compared to sons of non-smokers. Stratifying for maternal smoking habits across two pregnancies, there was an increased risk of poor intellectual performance for both sons if the mother was only smoking in the first pregnancy, but in neither son if the mother was only smoking in the second pregnancy. The effect of smoking during pregnancy on intellectual performance was not present when the association was evaluated within sibling pairs. Thus, the association between prenatal smoking exposure and offspring risk of low intellectual performance appears to be completely confounded by familial (genetic and early environmental) factors.
doi:10.1111/j.1365-3016.2009.01073.x
PMCID: PMC3653250  PMID: 20078833
4.  Familial Confounding of the Association Between Maternal Smoking during Pregnancy and Offspring Substance Use and Problems: Converging Evidence Across Samples and Measures 
Archives of general psychiatry  2012;69(11):1140-1150.
Context
Previous epidemiological, animal, and human cognitive neuroscience research suggests that maternal smoking during pregnancy causes increased risk of offspring substance use/problems.
Objective
To determine the extent to which the association between SDP and offspring substance use/problems depends on confounded familial background factors by using a quasi-experimental design.
Design
We used two separate samples, from the United States and from Sweden, respectively. The analyses prospectively predicted multiple indices of substance use and problems while controlling for statistical covariates and comparing differentially exposed siblings to minimize confounding.
Setting
Sample 1: Offspring of a representative sample of women in the United States. Sample 2: The total Swedish population born over 13 years.
Patients or Other Participants
Sample 1: Adolescent offspring of the women in the National Longitudinal Survey of Youth 1979 (n=6,094). Sample 2: All offspring born in Sweden from 1983 through 1995 (n=1,187,360).
Main Outcome Measures
Sample 1: Self-reported adolescent alcohol, cigarette, and marijuana use, and early onset (before age 14 years) of each substance. Sample 2: Substance-related convictions and hospitalizations for an alcohol- or drug-related problem.
Results
The same pattern emerged for each index of substance use/problems across the two samples. At the population level maternal smoking during pregnancy predicted every measure of offspring substance use/problems in both samples, ranging from adolescent alcohol use (HRmoderate=1.32, CI=1.22–1.43; HRhigh=1.33, CI=1.17=1.53) to a narcotic convictions (HRmoderate=2.23, CI=2.14–2.31; HRhigh=2.97, CI=2.86–3.09). When comparing differentially exposed siblings to minimize genetic and environmental confounds, however, the association between SDP and each measure of substance use/problems was minimal and not statistically significant.
Conclusions
The association between maternal smoking during pregnancy and offspring substance use/problems was likely due to familial background factors, not a causal influence, because siblings had similar rates of substance use and problems regardless of their specific exposure to smoking during pregnancy.
doi:10.1001/archgenpsychiatry.2011.2107
PMCID: PMC3622274  PMID: 23117635
5.  Genetic Influences Are Important for Most But Not All Lower Urinary Tract Symptoms: A Population-Based Survey in a Cohort of Adult Swedish Twins 
European urology  2011;59(6):1032-1038.
Background
The relative importance of genetic and environmental factors for the occurrence of lower urinary tract symptoms (LUTS) is poorly understood.
Objective
To (1) estimate the prevalence of urinary incontinence (UI), overactive bladder (OAB), and other LUTS and (2) to assess the heritability of these symptoms.
Design, setting, and participants
Cross-sectional survey of LUTS in a national population-based cohort of Swedish twins 20–46 yr of age (n = 42 582) from the Swedish Twin Registry.
Measurements
Prevalence rates were determined and heritability of LUTS (in female twins) was assessed using indicators of twin similarity.
Results and limitations
A total of 25 364 twins completed the questionnaire (response rate: 59.6%). LUTS were more common in women (UI: 7%; OAB: 9%; nocturia: 61%; micturition frequency: 18%) than in men (UI: 1%; OAB: 5%; nocturia: 40%; micturition frequency: 11%), and prevalence increased with age. The strongest genetic effects were observed for UI, frequency, and nocturia. The lowest estimate for genetic effects was observed for OAB where environmental effects dominated, and more specifically shared family environment accounted for a third or more of the total variation. For stress UI, a fifth of the total variation in susceptibility to the disorder could be attributed to shared environment. Nonshared environmental effects were seen in the range of 45–65% for the various LUTS. The prevalence of LUTS was low in the men, and there were too few male cases to compute measures of similarity or heritability estimates.
Conclusions
This study provides robust evidence of a genetic influence for susceptibility to UI, frequency, and nocturia in women. In contrast, shared environmental factors seem more important for the predisposition to develop OAB, which may reflect familial patterns such as learning from parental behaviours.
doi:10.1016/j.eururo.2011.03.007
PMCID: PMC3101479  PMID: 21420232
6.  Influence of smoking, coffee and tea consumption on bladder pain syndrome in female twins 
Urology  2011;77(6):1313-1317.
OBJECTIVES
To assess the influence of smoking, coffee and tea consumption on the risk for bladder pain syndrome (BPS) using the O'Leary Interstitial Cystitis Symptom Index (ICSI)
METHODS
In 2005, all twins born 1959–1985 in Sweden (n = 42 852) were invited to participate in a web-based survey to screen for complex diseases including BPS. Analyses were limited to female twins with information regarding bladder pain symptoms (n = 9 349). Women with an ICSI score of 6 or greater with required nocturia and bladder pain were defined as having BPS symptoms. Logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Environmental and genetic influences were assessed in co-twin control analysis
RESULTS
Tea consumption was associated with an increased risk for BPS (OR 1.26, 95% CI 1.02–1.55 for low tea consumption; OR 1.74, 95% CI 1.24–2.44 for high tea consumption). Coffee consumption was not a risk factor for BPS (OR 1.1, 95% CI 0.84–1.45). Former, and current smoking, were both associated with a higher risk of BPS (OR 1.5, 95% CI 1.18–1.89; and OR 1.49, 95% CI 1.16–1.92 respectively) but results from co-twin control analysis suggested that the association between smoking and BPS was confounded by familial factors.
CONCLUSIONS
Tea and smoking are environmental risk factors for BPS which are amenable to intervention. The effects of smoking on the risk for BPS may, however, be confounded by familial factors
doi:10.1016/j.urology.2010.12.072
PMCID: PMC3105162  PMID: 21439616
Bladder pain syndrome; Coffee; Smoking; Tea; Twins
7.  Prenatal smoking exposure and offspring stress coping in late adolescence: no causal link 
Background In utero exposure to tobacco smoking has been suggested to cause persistent alterations in cognitive functioning. We examined if mothers’ smoking during pregnancy (SDP) is associated with long-term impairment in offspring stress coping and the causal mechanism behind a possible link.
Methods We used a large cohort (n = 187 106) of young males in Sweden (mean age = 18.2 years), who underwent a semi-structured psychological assessment in 1997–2006, including an evaluation of stress coping ability, as part of the compulsory military conscript examination. We compared differentially exposed siblings within nuclear families and cousins in extended families and used multilevel structural equation models to disentangle genetic from environmental contributions to the association between SDP and stress coping.
Results SDP and offspring stress coping was moderately strongly associated when comparing unrelated individuals [regression coefficient (b) = −0.38 on a nine-point scale; 95% confidence interval (CI) −0.40 to −0.36, P < 0.0001]. In contrast, it disappeared when siblings were compared (b = 0.11; 95% CI −0.01 to 0.23, P = 0.071). This familial confounding was entirely due to genetic influences.
Conclusions SDP is an established risk factor for pregnancy- and birth-related complications. However, we found no long-term effect of SDP on offspring stress coping. Rather, the observed association was due to familial confounding of genetic origin; women prone to SDP also transmit genes to their children that are associated with poorer coping with stress.
doi:10.1093/ije/dyq133
PMCID: PMC3031341  PMID: 20719746
Smoking during pregnancy; adolescent stress coping; children-of-sibling model; intergenerational association
8.  Ethnic differences in the association of Birth Weight and Blood Pressure -the Georgia Cardiovascular Twin Study 
American journal of hypertension  2007;20(12):1235-1241.
Background
African Americans (AA) not only have higher blood pressure levels, but also an increased risk of low weight at birth, compared to European Americans (EA). In light of fetal programming theories it has been suggested that ethnic differences in blood pressure originate in utero. However, most previous studies in bi-ethnic samples have not found a significant inverse association between birth weight and blood pressure in AAs.
Methods
In 562 EA and 465 AA adolescent twins of the Georgia Cardiovascular Twin Study we investigated the potential ethnic difference in blood pressure - birth weight association, with the ability to control for potential confounding by familial factors.
Results
Blood pressure levels were significantly higher in AAs compared to EAs, independent of birth weight (p<0.01). After adjustment for parental factors and BMI, the difference in systolic blood pressure per kg birth weight was -1.1 mm Hg (95% confidence interval -2.7, 0.48, p=0.17) in EAs and -2.5 mm Hg (95% CI -4.7, -0.40, p=0.02) in AAs. A significant ethnic interaction was revealed in paired analysis where the inverse association remained in AAs, but not in EAs. Associations with diastolic blood pressure were generally weaker and non significant.
Conclusion
We could show that low birth weight was associated with an elevated systolic blood pressure in AAs, independent of familial factors. The results also suggest that the association between birth weight and blood pressure may be more pronounced in AAs in adolescence.
doi:10.1016/j.amjhyper.2007.07.012
PMCID: PMC2924638  PMID: 18047911
Birth Weight; Blood Pressure; Fetal Programming; Ethnicity; Twins
9.  Genetic and environmental influence on lung function impairment in Swedish twins 
Respiratory Research  2010;11(1):92.
Background
The understanding of the influence of smoking and sex on lung function and symptoms is important for understanding diseases such as COPD. The influence of both genes and environment on lung function, smoking behaviour and the presence of respiratory symptoms has previously been demonstrated for each of these separately. Hence, smoking can influence lung function by co-varying not only as an environmental factor, but also by shared genetic pathways. Therefore, the objective was to evaluate heritability for different aspects of lung function, and to investigate how the estimates are affected by adjustments for smoking and respiratory symptoms.
Methods
The current study is based on a selected sample of adult twins from the Swedish Twin Registry. Pairs were selected based on background data on smoking and respiratory symptoms collected by telephone interview. Lung function was measured as FEV1, VC and DLco. Pack years were quantified, and quantitative genetic analysis was performed on lung function data adjusting stepwise for sex, pack years and respiratory symptoms.
Results
Fully adjusted heritability for VC was 59% and did not differ by sex, with smoking and symptoms explaining only a small part of the total variance. Heritabilities for FEV1 and DLco were sex specific. Fully adjusted estimates were10 and 15% in men and 46% and 39% in women, respectively. Adjustment for smoking and respiratory symptoms altered the estimates differently in men and women. For FEV1 and DLco, the variance explained by smoking and symptoms was larger in men. Further, smoking and symptoms explained genetic variance in women, but was primarily associated with shared environmental effects in men.
Conclusion
Differences between men and women were found in how smoking and symptoms influence the variation in lung function. Pulmonary gas transfer variation related to the menstrual cycle has been shown before, and the findings regarding DLco in the present study indicates gender specific environmental susceptibility not shown before. As a consequence the results suggest that patients with lung diseases such as COPD could benefit from interventions that are sex specific.
doi:10.1186/1465-9921-11-92
PMCID: PMC2914039  PMID: 20604964
10.  Diabetes and Obesity-Related Risks for Pelvic Reconstructive Surgery in a Cohort of Swedish Twins  
Diabetes Care  2008;31(10):1997-1999.
OBJECTIVE—To determine the diabetes- and obesity-related risks for surgically managed stress urinary incontinence and pelvic organ prolapse.
RESEARCH DESIGN AND METHODS—This twin cohort study used the Swedish Twin Register to identify 8,443 female twin pairs born from 1926 through 1958. The association between diabetes and pelvic floor surgery was estimated while taking into account the correlated (twin) structure of the data.
RESULTS—For type 1 and type 2 diabetes, no significant associations were observed for stress urinary incontinence (odds ratio [OR] 1.0 [95% CI 0.1–9.2] and 2.0 [1.0–4.0], respectively). There were no cases of prolapse surgery in type 1 diabetic subjects, and for type 2 diabetes the risk estimate was nonsignificant (1.6 [1.0–2.7]). BMI >25 kg/m2, age ≥60 years, and childbirth were the strongest risk factors for having incontinence surgery.
CONCLUSIONS—Our data suggest that diabetes is not associated with stress urinary incontinence or pelvic organ prolapse surgery.
doi:10.2337/dc08-0988
PMCID: PMC2551642  PMID: 18628571

Results 1-10 (10)