Search tips
Search criteria

Results 1-25 (254)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
more »
1.  The association of birth order with later body mass index and blood pressure: a comparison between prospective cohort studies from the UK and Brazil 
Previous studies have found greater adiposity and cardiovascular risk in first born children. The causality of this association is not clear. Examining the association in diverse populations may lead to improved insight.
We examine the association between birth order and body mass index (BMI), systolic and diastolic blood pressure (SBP/DBP) in the 2004 Pelotas cohort from southern Brazil and the Avon Longitudinal Study of Parents and Children (ALSPAC) from Bristol, south west England, restricting analysis to families with two children in order to remove confounding by family size.
No consistent differences in BMI, SBP or DBP were observed comparing first and second born children. Within the Pelotas 2004 cohort, first born females were thinner, with lower SBP and DBP; e.g. mean difference in SBP comparing first with second born was -0.979 (95% confidence interval -2.901 to 0.943). In ALSPAC, first born females had higher BMI, SBP and DBP. In both cohorts, associations tended to be in the opposite direction in males, although no statistical evidence for gender interactions was found.
The findings do not support an association between birth order and BMI or blood pressure. Differences to previous studies may be explained by differences in populations and/or confounding by family size in previous studies.
PMCID: PMC4024316  PMID: 24097298
ALSPAC; birth order; blood pressure; body mass index; cardiovascular; obesity; Pelotas; siblings
2.  Is there an intrauterine influence on obesity? Evidence from parent–child associations in the Avon Longitudinal Study of Parents and Children (ALSPAC) 
Archives of Disease in Childhood  2007;92(10):876-880.
It has been suggested that increasing obesity levels in young women lead to intrauterine environments that, in turn, stimulate increased obesity among their offspring, generating an intergenerational acceleration of obesity levels. If this mechanism is important, the association of maternal body mass index (BMI) with offspring BMI should be stronger than the association of paternal with offspring BMI.
To compare the relative strengths of association of maternal and paternal BMI with offspring BMI at age 7.5, taking into account the possible effect of non‐paternity.
We compared strength of association for maternal–offspring and paternal–offspring BMI for 4654 complete parent–offspring trios in the Avon Longitudinal Study of Parents and Children (ALSPAC), using unstandardised and standardised regression analysis. We carried out a sensitivity analysis to investigate the influence of non‐paternity on these associations.
The strength of association between parental BMI and offspring BMI at age 7.5 was similar for both parents. Taking into account correlations between maternal and paternal BMI, performing standardised rather than unstandardised regression and carrying out a sensitivity analysis for non‐paternity emphasised the robustness of the general similarity of the associations. The associations between high parental BMI (top decile) and offspring BMI are also similar for both parents.
Comparison of mother–offspring and father–offspring associations for BMI suggests that intergenerational acceleration mechanisms do not make an important contribution to levels of childhood BMI within the population. Associations at later ages and for different components of body composition now require study.
PMCID: PMC2083247  PMID: 17595200
3.  Personal View 
BMJ : British Medical Journal  1991;303(6801):528.
PMCID: PMC1670811
4.  Change in sleep duration and type 2 diabetes: the Whitehall II study 
Diabetes care  2015;38(8):1467-1472.
Evidence suggests that short and long sleep are associated with a higher risk of type 2 diabetes. Using successive data waves spanning more than 20 years we examined whether a change in sleep duration is associated with incident diabetes.
Research Design and Methods
Sleep duration was reported at the beginning and end of four 5-year cycles: 1985-88 to 1991-94 (N=5613); 1991-94 to 1997-99 (N=4193); 1997-99 to 2002-04 (N=3840); 2002-04 to 2007-09 (N=4195). At each cycle, change in sleep duration was calculated for participants without diabetes. Incident diabetes at the end of the subsequent 5-year period was defined using: (1) fasting glucose; (2) 75g oral glucose tolerance test; and (3) glycated hemoglobin, in conjunction with diabetes medication and self-reported doctor diagnosis.
Compared to the reference group of persistent 7-hour sleepers, an increase of ≥2hours sleep per night was associated with a higher risk of incident diabetes; Odds Ratios (95% Confidence Intervals) 1.65 (95% CI: 1.15, 2.37), in analyses adjusted for age, sex, employment grade and ethnic group. This association was partially attenuated by adjustment for body mass index and change in weight; 1.50 (1.04, 2.16). An increased risk of incident diabetes was also seen in persistent short sleepers (average ≤5.5 hours/night); 1.35 (1.04, 1.76), but this evidence weakened on adjustment for body mass index and change in weight; 1.25 (0.96, 1.63).
This study suggests that individuals whose sleep duration increases are at an increased risk of type 2 diabetes. Greater weight and weight gain in this group partly explain the association.
PMCID: PMC4512137  PMID: 26068863
5.  Psychological interventions for coronary heart disease 
Psychological interventions can form part of comprehensive cardiac rehabilitation programmes (CCR). These interventions may include stress management interventions, which aim to reduce stress, either as an end in itself or to reduce risk for further cardiac events in patients with heart disease.
To determine the effectiveness of psychological interventions, in particular stress management interventions, on mortality and morbidity, psychological measures, quality of life, and modifiable cardiac risk factors, in patients with coronary heart disease (CHD).
Search strategy
We searched CCTR to December 2001 (Issue 4, 2001), MEDLINE 1999 to December 2001 and EMBASE 1998 to the end of 2001, PsychINFO and CINAHL to December 2001. In addition, searches of reference lists of papers were made and expert advice was sought.
Selection criteria
RCTs of non-pharmacological psychological interventions, administered by trained staff, either single modality interventions or a part of CCR with minimum follow up of 6 months. Adults of all ages with CHD (prior myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina pectoris or coronary artery disease defined by angiography). Stress management (SM) trials were identified and reported in combination with other psychological interventions and separately.
Data collection and analysis
Studies were selected, and data were abstracted, independently by two reviewers. Authors were contacted where possible to obtain missing information.
Main results
Thirty six trials with 12,841 patients were included. Of these, 18 (5242 patients) were SM trials. Quality of many trials was poor with the majority not reporting adequate concealment of allocation, and only 6 blinded outcome assessors. Combining the results of all trials showed no strong evidence of effect on total or cardiac mortality, or revascularisation. There was a reduction in the number of non-fatal reinfarctions in the intervention group (OR 0.78 (0.67, 0.90), but the two largest trials (with 4809 patients randomized) were null for this outcome, and there was statistical evidence of publication bias. Similar results were seen for the SM subgroup of trials. Provision of any psychological intervention or SM intervention caused small reductions in anxiety and depression. Few trials reported modifiable cardiac risk factors or quality of life.
Authors’ conclusions
Overall psychological interventions showed no evidence of effect on total or cardiac mortality, but did show small reductions in anxiety and depression in patients with CHD. Similar results were seen for SM interventions when considered separately. However, the poor quality of trials, considerable heterogeneity observed between trials and evidence of significant publication bias make the pooled finding of a reduction in non-fatal myocardial infarction insecure.
PMCID: PMC4170898  PMID: 15106183
*Psychotherapy; Coronary Disease [mortality; *psychology; rehabilitation]; Stress, Psychological [*therapy]; Humans
6.  Statins for the primary prevention of cardiovascular disease 
Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease (CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with coronary artery disease. The case for primary prevention, however, is less clear.
To assess the effects, both harms and benefits, of statins in people with no history of CVD.
Search methods
To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007) and EMBASE (2003 to March 2007). There were no language restrictions.
Selection criteria
Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included.
Data collection and analysis
Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals) were calculated.
Main results
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.84, 95% CI 0.73 to 0.96) as was combined fatal and non-fatal CVD endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
Authors’ conclusions
Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of cancers or muscle pain among people without evidence of cardiovascular disease treated with statins. Other potential adverse events were not reported and some trials included people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
PMCID: PMC4164175  PMID: 21249663
Cardiovascular Diseases [blood; *prevention & control]; Cause of Death; Cholesterol, HDL [blood]; Cholesterol, LDL [blood]; Hydroxymethylglutaryl-CoA Reductase Inhibitors [adverse effects; *therapeutic use]; Primary Prevention; Randomized Controlled Trials as Topic; Adult; Humans
7.  Using genetic proxies for lifecourse sun exposure to assess the causal relationship of sun exposure with circulating vitamin D and prostate cancer risk 
Ecological and epidemiological studies have identified an inverse association of intensity and duration of sunlight exposure with prostate cancer, which may be explained by a reduction in vitamin D synthesis. Pigmentation traits influence sun exposure and therefore may affect prostate cancer risk. Because observational studies are vulnerable to confounding and measurement error, we used Mendelian randomization to examine the relationship of sun exposure with both prostate cancer risk and the intermediate phenotype, plasma levels of vitamin D.
We created a tanning, a skin color and a freckling score as combinations of SNPs that have been previously associated with these phenotypes. A higher score indicates propensity to burn, have a lighter skin color and freckles. The scores were tested for association with vitamin D levels (25-hydroxyvitamin-D and 1,25-dihydroxyvitamin-D) and PSA-detected prostate cancer in 3123 white British individuals enrolled in the Prostate Testing for cancer and Treatment (ProtecT) study.
The freckling score was inversely associated with 25(OH)D levels (change in 25(OH)D per score unit −0.27; 95%CI: −0.52, −0.01), and the tanning score was positively associated with prostate cancer risk (OR 1.05; 95%CI: 1.02,1.09), after adjustment for population stratification and potential confounders.
Individuals who tend to burn are more likely to spend less time in the sun and consequently have lower plasma vitamin D levels and higher susceptibility to prostate cancer.
The use of pigmentation related genetic scores is valuable for the assessment of the potential benefits of sun exposure with respect to prostate cancer risk.
PMCID: PMC3616836  PMID: 23441100
pigmentation; tanning; sun exposure; vitamin D; prostate cancer
8.  Is chronic fatigue syndrome (CFS/ME) heritable in children, and if so, why does it matter? 
Archives of Disease in Childhood  2007;92(12):1058-1061.
We need a clear definition of CFS/ME in children and sample sizes for genetic studies need to be much larger
PMCID: PMC2066085  PMID: 17804594
9.  Childhood and adulthood socioeconomic position across 20 causes of death: a prospective cohort study of 800 000 Norwegian men and women 
To assess the impact of childhood and adulthood socioeconomic position (SEP) across 20 causes of death in a large population‐wide sample of Norwegian men and women.
Census data on parental occupational class from 1960 and data from the tax register on household income in 1990 were linked to the death register for 1990–2001, and 20 causes of death were studied. Relative indices of inequalities were computed. Norwegians in the age group 0–20 years in 1960 and still alive in 1990 were followed for deaths in 1990 to 2001. This follow up involved 795 324 individuals (78%) and 20 887 deaths.
Main results
In men most support for an effect of childhood socioeconomic position was found for stomach cancer, lung cancer, coronary heart disease, “other violent death”, and all causes of death. In women similar effects were found for lung cancer, cervical cancer, coronary heart disease, chronic obstructive pulmonary disease, and all causes of death.
The effect of childhood socioeconomic position relative to adulthood varies by cause of death. Although there are some exceptions, the patterns in men and women are generally similar.
PMCID: PMC2465604  PMID: 17933960
life course epidemiology; social inequality; cause‐specific mortality
10.  Associations between tooth loss and mortality patterns in the Glasgow Alumni Cohort 
Heart  2006;93(9):1098-1103.
To use data from the Glasgow Alumni Cohort to investigate whether oral health in young adulthood is independently associated with later life cardiovascular disease (CVD) and cancer mortality.
Methods and results
Of the original cohort (n = 15 322), 12 631 subjects were traced through the National Health Service Central Register. Of these, 9569 men and 2654 women were 30 years or younger at baseline. During up to 57 years of follow‐up, 1432 deaths occurred among subjects with complete data, including 509 deaths from CVD and 549 from cancer. After adjusting for potential confounders, no substantial association was found between the number of missing teeth (as a continuous variable) and all‐cause mortality (hazard ratio (HR) for each extra missing tooth  = 1.01; 95% confidence interval (CI) 1.00 to 1.02), CVD mortality (HR = 1.01; 95% CI 0.99 to 1.03) or cancer mortality (HR = 1.00; 95% CI 0.98 to 1.02). When the number of missing teeth was treated as a categorical variable, there was evidence that students with nine or more missing teeth at baseline had an increased risk of CVD (HR = 1.35; 95% CI 1.03 to 1.77) compared with those with fewer than five missing teeth. When the number of missing teeth was transformed using fractional polynomials, there seemed to be a non‐linear relation between missing teeth and CVD mortality.
Although some evidence was found to support the relation between tooth loss and CVD mortality, causal mechanisms underlying this association remain uncertain.
PMCID: PMC1955024  PMID: 17164486
tooth loss; cardiovascular diseases; stroke; coronary heart diseases; mortality
12.  Does consideration of either psychological or material disadvantage improve coronary risk prediction? Prospective observational study of Scottish men 
To assess the value of psychosocial risk factors in discriminating between individuals at higher and lower risk of coronary heart disease, using risk prediction equations.
Prospective observational study.
5191 employed men aged 35 to 64 years and free of coronary heart disease at study enrolment
Main outcome measures
Area under receiver operating characteristic (ROC) curves for risk prediction equations including different risk factors for coronary heart disease.
During the first 10 years of follow up, 203 men died of coronary heart disease and a further 200 were admitted to hospital with this diagnosis. Area under the ROC curve for the standard Framingham coronary risk factors was 74.5%. Addition of “vital exhaustion” and psychological stress led to areas under the ROC curve of 74.5% and 74.6%, respectively. Addition of current social class and lifetime social class to the standard Framingham equation gave areas under the ROC curve of 74.6% and 74.9%, respectively. In no case was there strong evidence for improved discrimination of the model containing the novel risk factor over the standard model.
Consideration of psychosocial risk factors, including those that are strong independent predictors of heart disease, does not substantially influence the ability of risk prediction tools to discriminate between individuals at higher and lower risk of coronary heart disease.
PMCID: PMC2660009  PMID: 17699540
cardiovascular disease; risk assessment; Framingham risk score; primary prevention; psychosocial factors
13.  Reproducibility measures and their effect on diet–cancer associations in the Boyd Orr cohort 
To quantify measurement error in the estimation of family diet intakes using 7‐day household food inventories and to investigate the effect of measurement‐error adjustment on diet–disease associations.
Design and setting
Historical cohort study in 16 districts in England and Scotland, between 1937 and 1939.
4999 children from 1352 families in the Carnegie Survey of Diet and Health. 86.6% of these children were traced as adults and form the Boyd Orr cohort. The reproducibility analysis was based on 195 families with two assessments of family diet recorded 3–15 months apart.
Intraclass correlation coefficients (ICCs) were calculated for a variety of nutrients and food groups. Diet–cancer associations reported previously in the Boyd Orr cohort were reassessed using two methods: (a) the ICC and (b) the regression calibration.
Main results
The ICCs for the dietary intakes ranged from 0.44 (β carotene) to 0.85 (milk and milk products). The crude fully adjusted hazard ratio (HR) for cancer mortality per 1 MJ/day increase in energy intake was 1.15 (95% CI 1.06 to 1.24). After adjustment using the ICC for energy (0.80) the HR (95% CI) increased to 1.19 (1.08 to 1.31), and the estimate from regression calibration was 1.14 (0.98 to 1.32). The crude fully adjusted odds ratio (OR) for cancer incidence per 40 g/day increase in fruit intake was 0.84 (95% CI 0.73 to 0.97). After adjustment using the fruit ICC (0.78) it became 0.81 (0.67 to 0.96) and the OR derived from regression calibration was 0.81 (0.59 to 1.10).
The diet–disease relationships for the dietary intakes with low measurement error were robust to adjustment for measurement error.
PMCID: PMC2465690  PMID: 17435211
14.  Effect of conjugal bereavement on mortality of the bereaved spouse in participants of the Renfrew/Paisley Study 
To investigate how loss of a spouse affects mortality risk in the bereaved partner.
Design and setting
Prospective cohort study in Renfrew and Paisley in Scotland.
4395 married couples aged 45–64 years when the study was carried out between 1972 and 1976.
The date of bereavement for the bereaved spouse was the date of death of his or her spouse. Bereavement could occur at any time during the follow‐up period, so it was considered as a time‐dependent exposure variable and the Cox proportional hazards model for time‐dependent variables was used. The relative rate (RR) of mortality was calculated for bereaved versus non‐bereaved spouses and adjusted for confounding variables.
Main outcome measures
Causes of death to 31 March 2004.
Bereaved participants were at higher risk than non‐bereaved participants of dying from any cause (RR 1.27; 95% CI 1.2 to 1.35). These risks remained but were attenuated after adjustment for confounding variables. There were raised RRs for bereaved participants dying of cardiovascular disease, coronary heart disease, stroke, all cancer, lung cancer, smoking‐related cancer, and accidents or violence. After adjustment for confounding variables, RRs remained higher for bereaved participants for all these causes except for mortality from lung cancer. There was no strong statistical evidence that the increased risks of death associated with bereavement changed with time after bereavement.
Conjugal bereavement, in addition to existing risk factors, is related to mortality risk for major causes of death.
PMCID: PMC2465697  PMID: 17435215
15.  Breast feeding in infancy and social mobility: 60‐year follow‐up of the Boyd Orr cohort 
Archives of Disease in Childhood  2007;92(4):317-321.
To assess the association of having been breast fed with social class mobility between childhood and adulthood.
Historical cohort study with a 60‐year follow‐up from childhood into adulthood.
16 urban and rural centres in England and Scotland.
3182 original participants in the Boyd Orr Survey of Diet and Health in Pre‐War Britain (1937–39) were sent follow‐up questionnaires between 1997 and 1998. Analyses are based on 1414 (44%) responders with data on breast feeding measured in childhood and occupational social class in both childhood and adulthood.
Main outcome
Odds of moving from a lower to a higher social class between childhood and adulthood in those who were ever breast fed versus those who were bottle fed.
The prevalence of breast feeding varied by survey district (range 45–86%) but not with household income (p = 0.7), expenditure on food (p = 0.3), number of siblings (p = 0.7), birth order (p = 0.5) or social class (p = 0.4) in childhood. Participants who had been breast fed were 41% (95% CI 10% to 82%) more likely to move up a social class in adulthood (p = 0.007) than bottle‐fed infants. Longer breastfeeding duration was associated with greater odds of upward social mobility in fully adjusted models (p for trend = 0.003). Additionally controlling for survey district, household income and food expenditure in childhood, childhood height, birth order or number of siblings did not attenuate these associations. In an analysis comparing social mobility among children within families with discordant breastfeeding histories, the association was somewhat attenuated (OR 1.16; 95% CI 0.74 to 1.8).
Breast feeding was associated with upward social mobility. Confounding by other measured childhood predictors of social class in adulthood did not explain this effect, but we cannot exclude the possibility of residual or unmeasured confounding.
PMCID: PMC2083668  PMID: 17301108
16.  Differentials and income-related inequalities in maternal depression during the first two years after childbirth: birth cohort studies from Brazil and the UK 
Depression is a prevalent health problem among women during the childbearing years. To obtain a more accurate global picture of maternal postnatal depression, studies that explore maternal depression with comparable measurements are needed. The aims of the study are: (1) to compare the prevalence of maternal depression in the first and second year postpartum between a UK and Brazilian birth cohort study; (2) to explore the extent to which variations in the rates were explained by maternal and infant characteristics, and (3) to investigate income-related inequalities in maternal depression after childbirth in both settings.
Population-based birth cohort studies were carried out in Avon, UK in 1991 (ALSPAC) and in the city of Pelotas, Brazil in 2004, where 13 798 and 4109 women were analysed, respectively. Self-completion questionnaires were used in the ALSPAC study while questionnaires completed by interviewers were used in the Pelotas cohort study. Three repeated measures of maternal depression were obtained using the Edinburgh Postnatal Depression Scale in the first and second year after delivery in each cohort. Unadjusted and adjusted analyses were carried out. The Relative index of Inequality was used for the analysis of income-relate inequalities so that results were comparable between cohorts.
At both the second and third time assessments, the likelihood of being depressed was higher among women from the Pelotas cohort study. These differences were not completely explained by differences in maternal and infant characteristics. Income-related inequalities in maternal depression after childbirth were high and of similar magnitude in both cohort studies at the three time assessments.
The burden of maternal depression after childbirth varies between and within populations. Strategies to reduce income-related inequalities in maternal depression should be targeted to low-income women in both developed and developing countries.
PMCID: PMC2698823  PMID: 19500361
17.  Socioeconomic position and overweight among adolescents: data from birth cohort studies in Brazil and the UK 
BMC Public Health  2009;9:105.
Developed and developing countries are facing rapid increases in overweight and obesity among children and adolescents. The patterns of overweight/obesity differ by age, sex, rural or urban residence and socioeconomic position (SEP) and vary between and within countries.
We investigated patterns of SEP – overweight status association among adolescents from the UK (ALSPAC) and Brazil (the 1982 and 1993 Pelotas birth cohort studies).
All analyses were performed separately for males and females. Logistic regression analysis was used to examine the relationships between overweight status and two SEP indicators – family income and maternal education.
A strong positive association was observed in 11-year-old boys from the 1993 Pelotas cohort, with higher prevalence of overweight among the least poor and among those whose mothers had more years of schooling (x2 for linear trend p < 0.001). In ALSPAC study higher prevalence of overweight was seen among boys whose mothers had lower educational achievement (x2 for linear trend p = 0.006). Among 11 year-old girls from 1993 Pelotas cohort study there was a positive association (higher prevalence of overweight in the higher socioeconomic and educational strata, x2 for linear trend p < 0.001 and p = 0.01, respectively) while an inverse association was found in the ALSPAC study (x2 for linear trend p < 0.001). Among males from the 1982 cohort study, overweight at 18 years of age showed a positive association with both SEP indicators while among females, the reverse association was found.
The results of this study demonstrate that the social patterning of overweight varies between and within populations over time. Specific approaches should be developed within populations in order to contain the obesity epidemic and reduce disparities.
PMCID: PMC2673220  PMID: 19368733
18.  The applicability of measures of socioeconomic position to different ethnic groups within the UK 
In this paper we seek to tease out differences in socioeconomic position between ethnic groups. There are 3 main reasons why conventional socioeconomic indicators and asset based measures may not be equally applicable to all ethnic groups:
1) Differences in response rate to conventional socioeconomic indicators
2) Cultural and social differences in economic priorities/opportunities
3) Differences in housing quality, assets and debt within socioeconomic strata
The sample consisted of White (n = 227), African-Caribbean (n = 213) and Indian and Pakistani (n = 233) adults aged between 18 and 59 years living in Leeds as measured in a stratified population survey. Measures included income, education, employment, car ownership, home ownership, housing quality, household assets, investments, debt, perceived ability to obtain various sums and perceived level of financial support given and received.
Response rates to education and income questions were similar for the different ethnic groups. Overall response rates for income were much lower than those for education and biased towards wealthier people. There were differences between ethnic groups in economic priorities/opportunities particularly in relation to car ownership, home ownership, investment and debt. Differences in living conditions, household assets and debt between ethnic groups were dependent on differences in education; however differences in car ownership, home ownership, ability to obtain £10 000, and loaning money to family/friends and income from employment/self employment persisted after adjustment for education.
In the UK, education appears to be an effective variable for measuring variation in SEP across ethnic groups but the ability to account for SEP differences may be improved by the addition of car and home ownership, ability to obtain £10 000, loaning money to family/friends and income from employment/self employment. Further research is required to establish the degree to which results of this study are generalisable.
PMCID: PMC2657895  PMID: 19250528
19.  Lactase persistence-related genetic variant: population substructure and health outcomes 
Lactase persistence is an autosomal-dominant trait that is common in European-derived populations. A basic tendency for lactase persistence to increase from the southeast to the northwest across European populations has been noted, but such trends within countries have not been extensively studied. We genotyped the C/T−13910 variant (rs4988235) that constitutes the putatively causal allele for lactase persistence (T allele representing persistence) in a general population sample of 3344 women aged 60–79 years from 23 towns across Britain. We found an overall frequency of 0.253 for the C (lactase non-persistence) allele, but with considerable gradients of decreasing frequency from the south to the north and from the east to the west of Britain for this allele. Daily sunlight was positively related to C (non-persistence) allele prevalence. However, sunlight exposure and latitude are strongly correlated, and it was not possible to identify which is the primary factor statistically underlying the distribution of lactase persistence. The C/T−13910 variant (rs4988235) was not related to drinking milk or bone health (although drinking milk itself was protective of bone health), and was essentially unrelated to a wide range of other lifestyle, health and demographic characteristics. One exception was general health being rated as being poor or fair, for which there was an odds ratio of 1.38 (1.04, 1.84) for women homozygous for the C allele; on adjustment for latitude and longitude of place of birth, this attenuated to 1.19 (0.87, 1.64). The lactase persistence variant could contribute to the examination of data for the existence of, and then statistical control for, population substructure in genetic association studies.
PMCID: PMC2986166  PMID: 18797476
lactase persistence; British Women's Heart and Health Study; bone health; population stratification; milk
20.  Inverse association between gastroesophageal reflux and blood pressure: Results of a large community based study 
BMC Gastroenterology  2008;8:10.
In a cross-sectional community based study, as part of a randomised controlled trial of eradication of Helicobacter pylori infection, the association between blood pressure and symptoms of gastro-oesophageal reflux was examined.
Linear regression was used to examine the association between systolic and diastolic blood pressure and the frequency of heartburn and acid regurgitation in 4,902 of 10,537 participants aged 20–59 years.
In multivariable analyses, adjusted mean systolic blood pressure was 4.2 (95% confidence interval 1.5 to 7.0) mm Hg lower in participants with daily acid regurgitation compared to those with less frequent symptoms. Similarly, for diastolic blood pressure, a reduction of 2.1 (0.0 to 4.3) mm Hg wasobserved.
People who experience daily symptoms of gastro-oesophageal reflux have lower blood pressure than people with less frequent or no symptoms. It is possible that factors influencing nitric oxide concentrations both at the lower oesophageal sphincter and within the vasculature may be involved. This hypothesis requires confirmation.
Trials registration number
PMCID: PMC2330142  PMID: 18412958
21.  Clustered Environments and Randomized Genes: A Fundamental Distinction between Conventional and Genetic Epidemiology  
PLoS Medicine  2007;4(12):e352.
In conventional epidemiology confounding of the exposure of interest with lifestyle or socioeconomic factors, and reverse causation whereby disease status influences exposure rather than vice versa, may invalidate causal interpretations of observed associations. Conversely, genetic variants should not be related to the confounding factors that distort associations in conventional observational epidemiological studies. Furthermore, disease onset will not influence genotype. Therefore, it has been suggested that genetic variants that are known to be associated with a modifiable (nongenetic) risk factor can be used to help determine the causal effect of this modifiable risk factor on disease outcomes. This approach, mendelian randomization, is increasingly being applied within epidemiological studies. However, there is debate about the underlying premise that associations between genotypes and disease outcomes are not confounded by other risk factors. We examined the extent to which genetic variants, on the one hand, and nongenetic environmental exposures or phenotypic characteristics on the other, tend to be associated with each other, to assess the degree of confounding that would exist in conventional epidemiological studies compared with mendelian randomization studies.
Methods and Findings
We estimated pairwise correlations between nongenetic baseline variables and genetic variables in a cross-sectional study comparing the number of correlations that were statistically significant at the 5%, 1%, and 0.01% level (α = 0.05, 0.01, and 0.0001, respectively) with the number expected by chance if all variables were in fact uncorrelated, using a two-sided binomial exact test. We demonstrate that behavioural, socioeconomic, and physiological factors are strongly interrelated, with 45% of all possible pairwise associations between 96 nongenetic characteristics (n = 4,560 correlations) being significant at the p < 0.01 level (the ratio of observed to expected significant associations was 45; p-value for difference between observed and expected < 0.000001). Similar findings were observed for other levels of significance. In contrast, genetic variants showed no greater association with each other, or with the 96 behavioural, socioeconomic, and physiological factors, than would be expected by chance.
These data illustrate why observational studies have produced misleading claims regarding potentially causal factors for disease. The findings demonstrate the potential power of a methodology that utilizes genetic variants as indicators of exposure level when studying environmentally modifiable risk factors.
In a cross-sectional study Davey Smith and colleagues show why observational studies can produce misleading claims regarding potential causal factors for disease, and illustrate the use of mendelian randomization to study environmentally modifiable risk factors.
Editors' Summary
Epidemiology is the study of the distribution and causes of human disease. Observational epidemiological studies investigate whether particular modifiable factors (for example, smoking or eating healthily) are associated with the risk of a particular disease. The link between smoking and lung cancer was discovered in this way. Once the modifiable factors associated with a disease are established as causal factors, individuals can reduce their risk of developing that disease by avoiding causative factors or by increasing their exposure to protective factors. Unfortunately, modifiable factors that are associated with risk of a disease in observational studies sometimes turn out not to cause or prevent disease. For example, higher intake of vitamins C and E apparently protected people against heart problems in observational studies, but taking these vitamins did not show any protection against heart disease in randomized controlled trials (studies in which identical groups of patients are randomly assigned various interventions and then their health monitored). One explanation for this type of discrepancy is known as confounding—the distortion of the effect of one factor by the presence of another that is associated both with the exposure under study and with the disease outcome. So in this example, people who took vitamin supplements might have also have exercised more than people who did not take supplements and it could have been the exercise rather than the supplements that was protective against heart disease.
Why Was This Study Done?
It isn't always possible to check the results of observational studies in randomized controlled trials so epidemiologists have developed other ways to minimize confounding. One approach is known as mendelian randomization. Several gene variants have been identified that affect risk factors. For example, variants in a gene called APOE affect the level of cholesterol in an individual's blood, a risk factor for heart disease. People inherit gene variants randomly from their parents to build up their own unique genotype (total genetic makeup). Consequently, a study that examines the associations between a gene variant and a disease can indicate whether the risk factor affected by that gene variant causes the disease. There should be no confounding in this type of study, the argument goes, because different genetic variants should not be associated with each other or with nongenetic variables that typically confound directly assessed associations between risk factors and disease. But is this true? In this study, the researchers have tested whether nongenetic risk factors are confounded by each other and also whether genetic variants are confounded by nongenetic risk factors and also by other genetic variants
What Did the Researchers Do and Find?
Using data collected in the British Women's Heart and Health Study, the researchers calculated how many pairs of nongenetic variables (for example, frequency of eating meat, alcohol intake) were significantly correlated with each other. That is, the number of pairs of nongenetic variables in which a high correlation between both variables occurred in more study participants than expected by chance. They compared this number with the number of correlations that would occur by chance if all the variables were totally independent. When the researchers assumed that 1 in 100 combinations of pairs of variables would have been correlated by chance, the ratio of observed to expected significant correlations was seen 45 times more frequently than would be expected by chance. When the researchers repeated this exercise with genetic variants, the ratio of observed to expected significant correlations was 1.58, a figure not significantly different from 1. Similarly, the ratio of observed to expected significant correlations when pairwise combinations between genetic and nongenetic variants were considered was 1.22.
What Do These Findings Mean?
These findings have two main implications. First, the large excess of observed over expected associations among the nongenetic variables indicates that many nongenetic modifiable factors occur in clusters—for example, people with healthy diets often have other healthy habits. Researchers doing observational studies always try to adjust for confounding but this result suggests that this adjustment will be hard to do, in part because it will not always be clear which factors are confounders. Second, the lack of a large excess of observed over expected associations among the genetic variables (and also among genetic variables paired with nongenetic variables) indicates that little confounding is likely to occur in studies that use mendelian randomization. In other words, this approach is a valid way to identify which environmentally modifiable risk factors cause human disease.
Additional Information.
Please access these Web sites via the online version of this summary at
Wikipedia has pages on epidemiology and on mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages).
Epidemiology for the Uninitiated is a primer from the British Medical Journal
Information is available on the British Women's Heart and Health Study
PMCID: PMC2121108  PMID: 18076282
23.  Resolving the Effects of Maternal and Offspring Genotype on Dyadic Outcomes in Genome Wide Complex Trait Analysis (“M-GCTA”) 
Behavior genetics  2014;44(5):445-455.
Genome wide complex trait analysis (GCTA) is extended to include environmental effects of the maternal genotype on offspring phenotype (“maternal effects”, M-GCTA). The model includes parameters for the direct effects of the offspring genotype, maternal effects and the covariance between direct and maternal effects. Analysis of simulated data, conducted in OpenMx, confirmed that model parameters could be recovered by full information maximum likelihood (FIML) and evaluated the biases that arise in conventional GCTA when indirect genetic effects are ignored. Estimates derived from FIML in OpenMx showed very close agreement to those obtained by restricted maximum likelihood using the published algorithm for GCTA. The method was also applied to illustrative perinatal phenotypes from ∼4,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children. The relative merits of extended GCTA in contrast to quantitative genetic approaches based on analyzing the phenotypic covariance structure of kinships are considered.
PMCID: PMC4174369  PMID: 25060210
Maternal effects; Genome wide complex trait analysis; GCTA; Twins; Heritability; Bias; Genetic relatedness; Covariance; Environment; SNPs
24.  Mortality cohort effects from mid-19th to mid-20th century Britain: did they exist? 
Annals of epidemiology  2014;24(8):570-574.
Identification is a central problem with age–period–cohort analysis. Because age + cohort = period, there is no unique solution to the linear effect using generalized linear modeling, but cohort effects have caused greater controversy than age and period effects. To illustrate the magnitude of cohort effects given the presence of collinearity, we reanalyze data from the seminal study by Kermack et al, with an update.
Relative mortality data in England and Wales between year 1845 and 1995 were analyzed using partial least squares regression. There were seven age groups ranging from 5 to 74 years old and 16 periods with 22 cohorts.
Our reanalysis seemed to support the existence of cohort effects in the mortality trends. Period and cohort effects were generally consistent with changes in the social, economic, and environmental factors taking place in the last two centuries. Our analysis also showed a declining trend in period effects up to 1950s.
Partial least squares and related methods provide intuitive pointers toward the separation of linear age, period, and cohort effects. Because statistical algorithms cannot distinguish between relative and actual mortality rates, cohort effects may be underestimated because of contamination by negative age effects.
PMCID: PMC4402224  PMID: 25084701
Age–period–cohort analysis; Mortality; Partial least squares; Cohort effects
25.  Fractional exhaled nitric oxide in childhood is associated with 17q11.2-q12 and 17q12-q21 variants 
The fractional concentration of nitric oxide in exhaled air (FeNO) is a biomarker of eosinophilic airway inflammation and associated with childhood asthma. Identification of common genetic variants associated with childhood FeNO may help to define biological mechanisms related to specific asthma phenotypes.
To identify genetic variants associated with childhood FeNO, and their relation with asthma.
FeNO was measured in children aged 5 to 15 years. In 14 genome-wide association (GWA) studies (N = 8,858), we examined the associations of ~2.5 million single nucleotide polymorphisms (SNPs) with FeNO. Subsequently, we assessed whether significant SNPs were expression quantitative trait loci (eQTLs) in genome-wide expression datasets of lymphoblastoid cell lines (N = 1,830), and were related with asthma in a previously published GWA dataset (cases: n=10,365; controls: n=16,110).
We identified 3 SNPs associated with FeNO: rs3751972 in LYR motif containing 9 (LYRM9) (P = 1.97×10−10) and rs944722 in inducible nitric oxide synthase 2 (NOS2) (P = 1.28×10−9) both located at 17q11.2-q12, and rs8069176 near gasdermin B (GSDMB) (P = 1.88×10−8) at 17q12-q21. We found a cis eQTL for the transcript soluble galactoside-binding lectin 9 (LGALS9) that is in linkage disequilibrium with rs944722. Rs8069176 was associated with GSDMB and ORM1-like 3 (ORMDL3) expression. Rs8069176 at 17q12-q21, and not rs3751972 and rs944722 at 17q11.2-q12, were associated with physician-diagnosed asthma.
This study identified 3 variants associated with FeNO, explaining 0.95% of the variance. Identification of functional SNPs and haplotypes in these regions might provide novel insight in the regulation of FeNO. This study highlights that both shared and distinct genetic factors affect FeNO and childhood asthma.
PMCID: PMC4334587  PMID: 24315451
airway inflammation; asthma phenotypes; biomarker; genetics; genome-wide association study

Results 1-25 (254)