Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study.

BACKGROUND: Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. METHODS: Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals. RESULTS: Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect. CONCLUSIONS: These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders.

Risk of cardiovascular disease in women and men with subfertility: the Trøndelag Health Study.

OBJECTIVE: To investigate the association between subfertility and risk of cardiovascular disease (CVD) outcomes. DESIGN: Prospective study. SETTING: Population-based cohort. PATIENT(S): We studied 31,629 women and 17,630 men participating in the Trøndelag Health Study. INTERVENTION(S): Self-reported subfertility. As men were not directly asked about fertility, male partners of female participants were identified through linkage to the Medical Birth Registry of Norway and assigned the fertility information obtained from their partners. MAIN OUTCOME MEASURE(S): The primary outcomes were stroke and coronary heart disease in women and men with and without a history of subfertility. The secondary outcomes were myocardial infarction and angina (subgroups of coronary heart disease) and any CVD (stroke or coronary heart disease). Information on CVD was available by linkage to hospital records. We used Cox proportional hazards models adjusted for age at participation in the Trøndelag Health Study (linear + squared), birth year, smoking history, cohabitation, and education. Cardiometabolic factors were assessed in separate models. RESULT(S): A total of 17% of women and 15% of men reported subfertility. In women, subfertility was modestly associated with an increased risk of stroke (age-adjusted hazard ratio [aaHR], 1.19; 95% confidence interval [CI], 1.02-1.39; adjusted hazard ratio [aHR]; 1.18; 95% CI, 1.01-1.37) and coronary heart disease (aaHR, 1.19; 95% CI, 1.06-1.33; aHR, 1.16; 95% CI, 1.03-1.30) compared with fertile women. In men, we observed a weak positive association for stroke (aaHR, 1.11; 95% CI, 0.91-1.34; aHR, 1.10; 95% CI, 0.91-1.33) and a weak inverse association for coronary heart disease (aaHR, 0.92; 95% CI, 0.81-1.05; aHR, 0.93; 95% CI, 0.81-1.06). CONCLUSION(S): We observed modestly increased risks of CVD outcomes in women and some weak associations in men, although with no strong statistical evidence on sex differences. We acknowledge that we were only able to include men linked to pregnancies ending at 12 completed gestational weeks or later, potentially resulting in selection bias and misclassification of history of subfertility in analyses of male partners. Despite the large sample size, our results indicate the need for larger studies to obtain precise results in both sexes and determine whether there are true sex differences.

The association between miscarriage and fecundability: the Norwegian Mother, Father and Child Cohort Study.

STUDY QUESTION: Is fecundability associated with miscarriage history and future miscarriage risk? SUMMARY ANSWER: Prior miscarriage was associated with lower fecundability, and participants with a history of subfertility (time-to-pregnancy (TTP) ≥12 months) were at a higher risk of subsequent miscarriage. WHAT IS KNOWN ALREADY: Although miscarriage and low fecundability share common risk factors, prior studies have reported both lower and higher fecundability after miscarriage. STUDY DESIGN, SIZE, DURATION: In this study, we examined two related associations: one, between miscarriage history and subsequent fecundability and, two, between fecundability and miscarriage risk in the subsequent pregnancy. The study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). In addition, the outcome of the pregnancy after the MoBa index pregnancy was obtained by linking information from three national health registries: the Medical Birth Registry of Norway, the Norwegian Patient Registry and the general practice database. PARTICIPANTS/MATERIALS, SETTING, METHODS: We examined the association between number of prior miscarriages and fecundability in 48 537 naturally conceived, planned pregnancies in participants with at least one prior pregnancy. We estimated fecundability ratios (FRs) and 95% CIs using proportional probability regression. We further estimated the relative risk (RR) of miscarriage in the subsequent pregnancy as a function of TTP in the MoBa index pregnancy for 7889 pregnancies using log-binomial regression. Multivariable analyses adjusted for maternal age, pre-pregnancy maternal BMI, smoking status, cycle regularity, income level and highest completed or ongoing education. MAIN RESULTS AND THE ROLE OF CHANCE: Fecundability decreased as the number of prior miscarriages increased. The adjusted FRs among women with one, two and three or more prior miscarriages were 0.83 (95% CI: 0.80-0.85), 0.79 (95% CI: 0.74-0.83) and 0.74 (95% CI: 0.67-0.82), respectively, compared with women with no prior miscarriages. Compared to women with a TTP of <3 months, the adjusted RR of miscarriage in the subsequent pregnancy was 1.16 (0.99-1.35) with TTP of 3-6 months, 1.18 (0.93-1.49) with TTP of 7-11 months and 1.43 (1.13-1.81) with TTP of 12 or more months. LIMITATIONS, REASONS FOR CAUTION: Information on TTP and prior miscarriages was obtained retrospectively, and TTP was self-reported. MoBa is a pregnancy cohort, and findings may not be generalizable to all women. We were unable to examine the effect of changing partners between pregnancies, as well as other paternal factors such as seminal parameters. We also did not know what proportion of our participants had changed partners between their prior pregnancies and the index pregnancy. Furthermore, it is likely that many early miscarriages are not recognized. WIDER IMPLICATIONS OF THE FINDINGS: The association between miscarriage and fecundability may reflect a contribution of occult pregnancy losses to TTP, as well as shared underlying causes for reduced fecundability and miscarriage. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Research Council of Norway through its Medical Student Research Program funding scheme (project number 271555/F20), its Centres of Excellence funding scheme (project number 262700) and through the project 'Women's fertility - an essential component of health and well-being' (project number 320656). M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement number 947684). A.J.W. is supported by the Intramural Program of the National Institute of Environmental Health Sciences at the National Institutes of Health, USA. The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Cardiovascular risk factors in extended family members and birthweight in offspring.

Low birthweight has been related to an increased risk of adult cardiovascular disease (CVD). Transgenerational studies have been used to investigate likely mechanisms underlying this inverse association. However, previous studies mostly examined the association of offspring birthweight with CVD risk factors among parents. In this study, we investigated the association between offspring birthweight and individual CVD risk factors, an index of CVD risk factors, and education in their parents, aunts/uncles, and aunts'/uncles' partners. Birth data (Medical Birth Registry, Norway (MBRN) (1967-2012)) was linked to CVD risk factor data (the County Study, Age 40 Program, and Cohort Norway (CONOR)) for the parents, aunts/uncles, and their partners. For body mass index (BMI), resting heart rate (RHR), systolic blood pressure (SBP), total cholesterol (TC), triglycerides (TG), and a risk factor index, the associations were examined by linear regression. For smoking and education, they were examined by logistic regression. Low birthweight was associated with an unfavorable risk factor profile in all familial relationships. For each kg increase in birthweight, the mean risk factor index decreased by -0.14 units (-0.15, -0.13) in mothers, -0.11 (-0.12, -0.10) in fathers, and -0.02 (-0.05, -0.00) to -0.07 (-0.09, -0.06) in aunts/uncles and their partners. The association in mothers was stronger than fathers, but it was also stronger in aunts/uncles than their partners. Profound associations between birthweight and CVD risk factors in extended family members were observed that go beyond the expected genetic similarities in pedigrees, suggesting that mechanisms like environmental factors, assortative mating, and genetic nurturing may explain these associations.

Alcohol Consumption, HDL-Cholesterol and Incidence of Colon and Rectal Cancer: A Prospective Cohort Study Including 250,010 Participants.

AIMS: Alcohol consumption has been linked to colorectal cancer (CRC) and also to the high-density lipoprotein cholesterol level (HDL-C). HDL-C has been associated with the incidence of CRC. The aim of this study was to investigate the association between self-reported alcohol consumption, HDL-C and incidence of CRC, separately for the two sites. METHODS: Altogether, 250,010 participants in Norwegian surveys have been followed-up for an average of 18 years with respect to a first-time outcome of colon or rectal cancer. During follow-up, 3023 and 1439 colon and rectal cancers were registered. RESULTS: For men, the HR per 1 drink per day was 1.05 with 95% confidence interval (0.98-1.12) for colon and 1.08 (1.02-1.15) for rectal cancer. The corresponding figures for women were 1.03 (0.97-1.10) and 1.05 (1.00-1.10). There was a positive association between alcohol consumption and HDL-C. HDL-C was inversely associated with colon cancer in men (0.74 (0.62-0.89) per 1 mmol/l) and positively associated with rectal cancer, although not statistically significant (1.15 (0.92-1.44). A robust regression that assigned weights to each observation and exclusion of weights ≤ 0.1 increased the HRs per 1 drink per day and decreased the HR per 1 mmol/l for colon cancer. The associations with rectal cancer remained unchanged. CONCLUSION: Our results support a positive association between alcohol consumption and colon and rectal cancer, most pronounced for rectal cancer. Considering the positive relation between alcohol consumption and HDL-C, the inverse association between HDL-C and colon cancer in men remains unsettled.

Childhood central nervous system tumors and leukemia: Incidence and familial risk. A comparative population-based study in Utah and Norway.

BACKGROUND: In this study, we aimed to evaluate incidence rates and family risk of the most common childhood cancers, tumors in the central nervous system (CNS), and leukemia among individuals from Norway and individuals with Scandinavian ancestry living in Utah. METHODS: We used the Utah Population Database and the Norwegian National Population Register linked to Cancer registries to identify cancers in children born between 1966 and 2015 and their first-degree relatives. We calculated incidence rates and hazards ratios. RESULTS: The overall incidence of CNS tumors increased with consecutive birth cohorts similarly in Utah and Norway (both P < 0.001). Incidence rates of leukemia were more stable and similar in both Utah and in Norway with 4.6/100 000 person-years among children (<15 years) born in the last cohort. A family history of CNS tumors was significantly associated with risk of childhood CNS tumors in Utah HR = 3.05 (95% CI 1.80-5.16) and Norway HR = 2.87 (95% CI 2.20-3.74). In Norway, children with a first-degree relative diagnosed with leukemia had high risk of leukemia (HR = 2.39, 95% CI 1.61-3.55). CONCLUSION: Despite geographical distance and assumed large lifestyle differences, two genetically linked pediatric populations show similar incidences of CNS tumors and leukemia in the period 1966-2015. CNS tumors and leukemia aggregated in families in both countries.

A population-based study of testicular cancer risk among children and young adults from Norway and Utah, USA.

Similar family-based cancer and genealogy data from Norway and Utah allowed comparisons of the incidence of testicular cancer (TC), and exploration of the role of Scandinavian ancestry and family history of TC in TC risk. Our study utilizes data from the Utah Population Database and Norwegian Population Registers. All males born during 1951-2015 were followed for TC until the age of 29 years. A total of 1,974,287 and 832,836 males were born in Norway and Utah, respectively, of whom 2,686 individuals were diagnosed with TC in Norway and 531 in Utah. The incidence per year of TC in Norway (10.6) was twice that observed in Utah (5.1) for males born in the last period (1980-1984). The incidence rates of TC in Utah did not differ according to the presence or absence of Scandinavian ancestry (p = 0.669). Having a brother diagnosed with TC was a strong risk factor for TC among children born in Norway and Utah, with HR = 9.87 (95% CI 5.68-17.16) and 6.02 (95% CI 4.80-7.55), respectively; with even higher HR observed among the subset of children in Utah with Scandinavian ancestry (HR = 12.30, 95% CI 6.78-22.31). A clear difference in TC incidence among individuals born in Norway and descendants of Scandinavian people born in Utah was observed. These differences in TC rates point to the possibility of environmental influence. Family history of TC is a strong risk factor for developing TC in both populations.

Birthweight in offspring and cardiovascular mortality in their parents, aunts and uncles: a family-based cohort study of 1.35 million births.

BACKGROUND: A link between suboptimal fetal growth and higher risk of cardiovascular disease (CVD) is well documented. It has been difficult to assess the contribution of environmental versus genetic factors to the association, as these factors are closely connected in nuclear families. We investigated the association between offspring birthweight and CVD mortality in parents, aunts and uncles, and examined whether these associations are explained by CVD risk factors. METHODS: We linked Norwegian data from the Medical Birth Registry, the Cause of Death Registry and cardiovascular surveys. A total of 1 353 956 births (1967-2012) were linked to parents and one maternal and one paternal aunt/uncle. Offspring birthweight and CVD mortality association among all relationships was assessed by hazard ratios (HR) from Cox regressions. The influence of CVD risk factors on the associations was examined in a subgroup. RESULTS: Offspring birthweight was inversely associated with CVD mortality among parents and aunts/uncles. HR of CVD mortality for one standard deviation (SD) increase in offspring birthweight was 0.72 (0.69-0.75) in mothers and 0.89 (0.86-0.92) in fathers. In aunts/uncles, the HRs were between 0.90 (0.86-0.95) and 0.93 (0.91-0.95). Adjustment for CVD risk factors in a subgroup attenuated all the associations. CONCLUSIONS: Birthweight was associated with increased risk of CVD in parents and in aunts/uncles. These associations were largely explained by CVD risk factors. Our findings suggest that associations between offspring birthweight and CVD in adult relatives involve both behavioural variables (especially smoking) and shared genetics relating to established CVD risk factors.

Early adulthood weight, subsequent midlife weight change and risk of cardiovascular disease mortality: an analysis of Norwegian cardiovascular surveys.

BACKGROUND: The time between early adulthood and midlife is important for obesity development. There is paucity of studies using objectively measured body mass index (BMI) at both time points with full range of midlife cardiovascular risk factors. We aimed to investigate the risk of cardiovascular disease (CVD) mortality associated with different levels of objectively measured change in body weight from early adulthood to midlife, and to assess whether risk is primarily explained by midlife cardiovascular risk factors. METHODS: Pooled data from Norwegian health surveys (1985-2003), Tuberculosis screenings, Conscript data and the Norwegian Educational database were linked to the Cause of Death Registry. Health survey participants with data on objectively measured weight and height in both early adulthood (18-20 years) and midlife (40-50 years) were included, n = 148,021. Cox regression models were used to assess associations between weight change and CVD mortality. RESULTS: Total analysis time included 2,841,174 person years. Mean follow-up was 19 (standard deviation 4) years. Participants being normal weight in early adulthood and obese in midlife had a hazard ratio (HR) of CVD mortality of 2.09 (95% CI 1.74-2.50) relative to those who were normal weight at both times. The corresponding HR of those being obese at both times was 5.15 (3.61-7.36). Adjustment for CVD risk factors attenuated these associations. Gaining ≥15 kg between early adulthood and midlife was associated with higher CVD mortality after adjustment for early adulthood weight (HR 1.51 (1.20-1.89)), and for smoking and education (HR 1.63 (1.30-2.04)), however not after adjustment for mediating CVD risk factors. CONCLUSIONS: Obesity both in early adulthood and in midlife was associated with CVD mortality. Weight gain of ≥15 kg from early adulthood to midlife was also associated with CVD mortality, but not after adjustment for mediating CVD risk factors.

The association between obesity and cardiovascular disease mortality in different strata of socioeconomic position: evidence from pooled Norwegian health surveys.

BACKGROUND: Socioeconomic position (SEP) is related to both obesity and cardiovascular disease (CVD). There is little evidence on whether SEP modifies the relation between obesity and CVD. The aim of the study was to investigate whether the association between obesity and CVD mortality is stronger among people with disadvantaged than among people with advantaged life course SEP. METHODS: Data from Norwegian population-based cardiovascular health surveys (1985-2003), including body mass index and CVD risk factors (cholesterol, blood pressure, smoking, current treatment for hypertension) were linked to socioeconomic indicators from register and census data (1960-90), and to the Cause of Death Registry (up until 2014). The total number of participants was 398 297. RESULTS: In comparison with normal weight, the age-adjusted hazard ratios and 95% confidence intervals of CVD mortality among obese participants were 2.39 (2.07-2.75) and 2.08 (1.70-2.53) among men and women with high SEP, respectively and 1.88 (1.60-2.21) and 1.75 (1.43-2.14) among men and women with low SEP. Adjustment for CVD risk factors attenuated the results in a similar manner in all SEP groups, and among both women and men. CONCLUSION: Obesity was consistently associated with a higher risk of CVD mortality, with only minor variation according to SEP. This means that preventing or treating obesity is, for the purpose of reducing CVD risk, equally important for an individual with high or low SEP.

Family history of cancer and risk of paediatric and young adult's testicular cancer: A Norwegian cohort study.

BACKGROUND: The aim of this study was to examine the association of a family history of cancer with the risk of testicular cancer in young adults. METHODS: This is a prospective cohort study including 1,974,287 males born 1951-2015, of whom 2686 were diagnosed with TC before the age of 30. RESULTS: A history of TC in male relatives was significantly associated with a diagnosis of TC among children and young adults, including brothers (6.3-fold), sons (4.7-fold), fathers (4.4-fold), paternal uncles (2.0-fold) and maternal uncles (1.9-fold). Individuals with a father diagnosed with a carcinoma or sarcoma showed an elevated risk (1.1-fold and 1.8-fold, respectively). A family history of mesothelioma was positively associated with a risk of TC [(father (2.8-fold), mother (4.6-fold) and maternal uncles and aunt (4.4-fold)]. Elevated risks were also observed when siblings were diagnosed with malignant melanoma (1.4-fold). The risk of TC was also increased when fathers (11.1-fold), paternal (4.9-fold) and maternal uncles and aunts (4.6-fold) were diagnosed with malignant neuroepithelial-tumours. CONCLUSION: We found an increased risk of TC among children and young adults with a family history of TC, carcinoma, mesothelioma, sarcoma, malignant melanoma and malignant neuroepithelial tumours. Hereditary cancer syndromes might underlie some of the associations reported in this study.

The educational gradient in premature cardiovascular mortality: Examining mediation by risk factors in cohorts born in the 1930s, 1940s and 1950s.

AIMS: Educational inequality in cardiovascular disease and in modifiable risk factors changes over time and between birth cohorts. We aimed to assess how cardiovascular disease risk factors mediate educational differences in premature cardiovascular disease mortality and how this varies over birth cohorts and sex. METHODS: We followed 360,008 40-45-year-olds born in the 1930s, 1940s or 1950s from Norwegian health examination surveys (1974-1997) for premature cardiovascular disease mortality. Cox proportional hazard and Aalen's additive survival analyses provided hazard ratios and rate differences of excess deaths in participants with basic versus tertiary education. RESULTS: Relative educational differences in premature cardiovascular disease mortality were stable, whereas absolute differences narrowed from the 1930s to the 1950s cohorts; rate differences per 100 000 person years declined from 170 (95% confidence interval 117, 224) to 49 (36, 61) in men and from 60 (34, 85) to 23 (16, 29) in women. Cardiovascular disease risk factors attenuated rate differences by 69% in both cohorts in men, and in women by 102% in 1930s and 61% in 1950s cohorts. Smoking had the single strongest influence on the educational differences for men in all three cohorts, and for women in the two most recent cohorts. CONCLUSION: Smoking appeared to be the driving force behind educational differences in premature cardiovascular disease mortality in the 1930s to 1950s birth cohorts for men and in the two recent birth cohorts for women. This suggests that strategies for smoking prevention and cessation might have the strongest impact for reducing educational inequality in premature cardiovascular disease mortality.

Educational inequalities in midlife risk factors for non-communicable diseases in two Norwegian counties 1974-2002.

Background: The absolute educational differences in the mortality of Norwegian women and men increased during 1960-2000 and thereafter levelled off in men, but continued to widen in women. Which of the risk factors for non-communicable diseases (NCDs) might explain these trends? Aim: The aim of this study was to investigate trends in gender-specific, absolute educational differences in established risk factors during 1974-2002. Methods: We used cross-sectional data from 40-45-year-old women and men who participated in one of three health surveys in two counties, from the years 1974-1978, 1985-1988 and 2001-2002. To account for increasing educational attainment through the period we used a regression-based index of inequality (Slope Index of Inequality) to assess the educational gradients over time. Results: From 1974 to 2002, the mean levels of serum total cholesterol and blood pressure decreased and body mass index (BMI) increased in all subgroups by education in both sexes. In men, the educational gradient tended to diminish toward the null for serum total cholesterol and narrowed for systolic blood pressure, but increased for BMI. In women, the educational gradient increased to the double for smoking and increased for triglycerides. Conclusions: In two Norwegian counties, the NCD risk factors showed dynamic patterns during 1974-2002. For blood pressure and serum total cholesterol, the levels showed consistent beneficial changes in all educational subgroups, with a narrowing tendency for educational gradients in men. In women, the educational gradient for smoking increased markedly. Knowledge on midlife trends in the educational gradients of risk factors may help to explain recent and future NCD mortality.

The association between BMI and mortality using early adulthood BMI as an instrumental variable for midlife BMI.

The article aims to describe the association between midlife body mass index (BMI) and cardiovascular disease (CVD)- and all-cause mortality, and to use early adulthood BMI as an instrumental variable for midlife BMI, in order to obtain an estimate less distorted by midlife confounders and reverse causality. Data from Norwegian health surveys (1974-2003) (midlife BMI, smoking, blood pressure, total cholesterol, heart rate), Military Conscription Records, National Tuberculosis Screenings (early adulthood BMI), National Educational Registry and Cause of Death Registry were linked. Participants with data on BMI in early adulthood and midlife were included (n = 148.886). Hazard Ratio (HR) for CVD mortality was higher in men with midlife obesity relative to normal weight (HR = 1.46(95% CI 1.25, 1.70). For all-cause mortality, HR was higher in those with obesity or underweight in midlife relative to normal weight (Men:HR = 1.19(95% CI 1.09, 1.29), HR = 2.49(95% CI 1.81, 3.43) Women:HR = 1.33(95% CI 1.13, 1.56), HR = 1.61(95% CI 1.22, 2.13)). In instrumental variable analyses, increased BMI became more strongly associated with CVD and all-cause mortality, and the increased risk of all-cause mortality among the underweight attenuated.

Cardiovascular risk profile at the age of 40-45 in women with previous hyperemesis gravidarum or hypertensive disorders in pregnancy: A population-based study.

OBJECTIVE: To assess midlife cardiovascular risk profiles in women with a history of hyperemesis or hypertensive disorders in pregnancy compared to women with none of the studied pregnancy complications. STUDY DESIGN: Population-based study. Cardiovascular risk factors at the age of 40-45 among women with previous singleton births only were studied through linkage of the Norwegian Birth Registry and a Norwegian screening program (the Age 40 Program). MAIN OUTCOME MEASURES: Family history of coronary heart disease, body mass index, smoking, physical activity, systolic and diastolic blood pressure, heart rate, cholesterol, triglycerides, antihypertensive treatment and diabetes. RESULTS: Among 178,231 women participating in the Age 40 Program with previous singleton births; 2140 (1.2%) had experienced hyperemesis and 13,348 (7.5%) hypertensive disorders in pregnancy. Women who had suffered from hyperemesis were less physically active. The differences in mean systolic blood pressure and body mass index were probably clinically irrelevant. In women with a history of hypertensive disorders in pregnancy, systolic and diastolic blood pressure and body mass index were higher, and they were more likely to report diabetes in midlife. Women who had suffered from hyperemesis or hypertensive disorders in pregnancy were less likely to be daily smokers. CONCLUSION: Women with hypertensive disorders in pregnancy seemed to have an unfavorable cardiovascular risk profile in midlife compared to women with uncomplicated pregnancies. In contrast there was no consistent evidence of increased risk subsequent to hyperemesis gravidarum. The proportion of daily smokers was lower in women with either of the two pregnancy complications.

Family history of cancer and the risk of childhood solid tumours: a Norwegian nationwide register-based cohort study.

This corrects the article DOI: 10.1038/bjc.2017.85.

Life course socioeconomic position, alcohol drinking patterns in midlife, and cardiovascular mortality: Analysis of Norwegian population-based health surveys.

BACKGROUND: Socioeconomically disadvantaged groups tend to experience more harm from the same level of exposure to alcohol as advantaged groups. Alcohol has multiple biological effects on the cardiovascular system, both potentially harmful and protective. We investigated whether the diverging relationships between alcohol drinking patterns and cardiovascular disease (CVD) mortality differed by life course socioeconomic position (SEP). METHODS AND FINDINGS: From 3 cohorts (the Counties Studies, the Cohort of Norway, and the Age 40 Program, 1987-2003) containing data from population-based cardiovascular health surveys in Norway, we included participants with self-reported information on alcohol consumption frequency (n = 207,394) and binge drinking episodes (≥5 units per occasion, n = 32,616). We also used data from national registries obtained by linkage. Hazard ratio (HR) with 95% confidence intervals (CIs) for CVD mortality was estimated using Cox models, including alcohol, life course SEP, age, gender, smoking, physical activity, body mass index (BMI), systolic blood pressure, heart rate, triglycerides, diabetes, history of CVD, and family history of coronary heart disease (CHD). Analyses were performed in the overall sample and stratified by high, middle, and low strata of life course SEP. A total of 8,435 CVD deaths occurred during the mean 17 years of follow-up. Compared to infrequent consumption (

The importance of early life family factors in the association between cardiovascular risk factors and early cardiovascular mortality.

OBJECTIVE: To explore the importance of early life factors shared by siblings, such as parental socioeconomic position, parental practices, housing and neighbourhood, for the association between cardiovascular disease (CVD) risk factors and mortality from CVD, ischaemic heart disease (IHD) and cerebrovascular disease. METHODS: Norwegian health surveys (1974-2003) were linked with data from the Norwegian Family Based Life Course Study and the Cause of Death Registry. Participants with at least one full sibling among survey participants (n=2 71 643) were included. Data on CVD risk factors, body mass index (BMI), height, systolic blood pressure (SBP) and total cholesterol (TC) were stratified into 'low', 'medium' and 'high' risk, and smoking to 'daily smoking' and 'not daily smoking'. RESULTS: Mean age of participants was 41 years, mean follow-up time was 19 years and during follow-up 2512 died from CVD. For each category of increased risk factor level, the per step HR of CVD mortality was increased by 1.91 (95% CI 1.78 to 2.05) for SBP, 1.67 (1.58 to 1.76) for TC, 1.44 (1.36 to 1.53) for BMI, 1.26 (1.18 to 1.35) for height and 2.89 (2.66 to 3.14) for smoking. In analyses where each sibship (groups of full siblings) had a group-specific baseline hazard, these associations were attenuated to 1.74, 1.51, 1.29, 1.18 and 2.63, respectively. The associations between risk factors and IHD mortality followed the same pattern. CONCLUSION: Early life family factors explained a small part of the association between risk factors and mortality from CVD and IHD in a relatively young sample.

Offspring sex and parental health and mortality.

Increased mortality has been observed in mothers and fathers with male offspring but little is known regarding specific diseases. In a register linkage we linked women born 1925-1954 having survived to age 50 (n = 661,031) to offspring and fathers (n = 691,124). Three approaches were used: 1) number of total boy and girl offspring, 2) sex of the first and second offspring and 3) proportion of boys to total number of offspring. A sub-cohort (n = 50,736 mothers, n = 44,794 fathers) from survey data was analysed for risk factors. Mothers had increased risk of total and cardiovascular mortality that was consistent across approaches: cardiovascular mortality of 1.07 (95% CI: 1.03-1.11) per boy (approach 2), 1.04 (1.01-1.07) if the first offspring was a boy, and 1.06 (1.01-1.10) if the first two offspring were boys (approach 3). We found that sex of offspring was not associated with total or cardiovascular mortality in fathers. For other diseases or risk factors no robust associations were seen in mothers or fathers. Increased cardiovascular risk in mothers having male offspring suggests a maternal disease specific mechanism. The lack of consistent associations on measured risk factors could suggest other biological pathways than those studied play a role in generating this additional cardiovascular risk.

The risk of cancer in the offspring and parental length of life.

BACKGROUND: We investigated if cancer onset in offspring is related to having short-lived parents for different cancer types and to see if there was a difference in smoking- and non-smoking related cancers. METHODS: Our study included 524,391 individuals born in Norway 1940-1950. All children were followed up for cancer from the age of 20 until they were between 59 and 69 years. Parental longevity was examined by grouping parental age of death into parents dying before 75 years of age and parents dying at 75 years of age or older. RESULTS: An increased risk of 1.14 (95%CI=1.10-1.19) among male offspring and 1.08 (95%CI=1.04-1.12) among female offspring was observed for total cancer when both parents died before the age of 75 compared to offspring with two long-lived parents. The highest increase was found for cancer in the lungs and trachea for both male (HR=1.67, 95%CI=1.50-1.86) and female offspring (HR=1.53, 95%CI=1.33-1.76). For other smoking-related cancers, the risk was lower. No increased risk was observed for non-smoking-related cancers. CONCLUSION: Offspring of long-lived parents have lower risk of developing cancer compared with offspring of short-lived parents. Intergenerational transmission of risk factors from parents to offspring may play an important role, especially for tobacco-related cancers. However, genetic factors cannot be ruled out, since consistent evidence has implicated genetic factors in smoking behaviour.