The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

An epigenome-wide association study meta-analysis of educational attainment.

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications-in our case, CpG methylation-and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Associations between sports participation, cardiorespiratory fitness, and adiposity in young adult twins.

Exercise behavior, cardiorespiratory fitness, and obesity are strongly influenced by genetic factors. By studying young adult twins, we examined to what extent these interrelated traits have shared genetic and environmental etiologies. We studied 304 twin individuals selected from the population-based FinnTwin16 study. Physical activity was assessed with the Baecke questionnaire, yielding three indexes: sport index, leisure-time index, and work index. In this study, we focused on sport index, which describes sports participation. Body composition was determined using dual-energy X-ray absorptiometry and cardiorespiratory fitness using a bicycle ergometer exercise test with gas exchange analysis. The Baecke sport index was associated with high maximal oxygen uptake adjusted for lean body mass (Vo(2max)[adj]) (r = 0.40), with low body fat percentage (BF%) (r = -0.44) and low waist circumference (WC) (r = -0.29). Heritability estimates for the key traits were as follows: 56% for sport index, 71% for Vo(2max)[adj], 77% for body mass index, 66% for WC, and 68% for BF%. The association between sport index and Vo(2max) was mostly explained by genetic factors (70%), as were both the association between sport index and BF% (71%) and that between sport index and WC (59%). Our results suggest that genetic factors explain a considerable part of the associations between sports participation, cardiorespiratory fitness, and obesity.

Genetic origins of the association between verbal ability and alcohol dependence symptoms in young adulthood.

BACKGROUND: Cognitive deficits in alcohol dependence (AD) have been observed, poorer verbal ability being among the most consistent findings. Genetic factors influence both cognitive ability and AD, but whether these influences overlap is not known. METHOD: A subset of 602 monozygotic (MZ) and dizygotic (DZ) twins from FinnTwin16, a population-based study of Finnish twins, was used to study the associations of verbal ability with DSM-III-R diagnosis and symptoms of AD, the maximum number of drinks consumed in a 24-h period, and the Rutgers Alcohol Problem Index (RAPI) scores. These twins, most of them selected for within-pair discordance or concordance for their RAPI scores at age 18.5 years, were studied with neuropsychological tests and interviewed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) in young adulthood (mean age 26.2 years, range 23-30 years). RESULTS: All alcohol problem measures were associated with lower scores on the Vocabulary subtest of the Wechsler Adult Intelligence Scale - Revised (WAIS-R), a measure of verbal ability. In bivariate genetic models, Vocabulary and the alcohol problem measures had moderate heritabilities (0.54-0.72), and their covariation could be explained by correlated genetic influences (genetic correlations -0.20 to -0.31). CONCLUSIONS: Poorer verbal ability and AD have partly overlapping biological etiology. The genetic and environmental influences on the development of cognitive abilities, alcohol problems and risk factors for AD should be studied further with prospective longitudinal designs.

Anaemia and other predictors of fatigue among patients on palliative therapy for advanced cancer.

The association of anaemia and other predictors of fatigue was studied in cancer patients on palliative treatment. A cohort of 128 consecutive patients (61 men and 67 women, mean age 63.6 years; range 36-85) was interviewed using the Edmonton Symptom Assessment System (ESAS) questionnaire, with 11 items describing cancer-related symptoms in visual analogue scale (VAS). Routine haematological samples were analysed at the time of interview. Both univariate and multivariate analyses were used to assess the independent predictors of fatigue. Out of the 10 symptoms recorded, fatigue was the single most frequent, reported by 91.3% of the patients, followed by pain (74.8%), sleeplessness (78.0%) and depression (74.2%). Anaemia was a significant determinant of fatigue (p=0.040)(OR=5.09; 95% CI 1.013-25.647). Out of the symptoms recorded, fatigue was significantly associated with depression (p=0.035), loss of appetite (p=0.016), anxiety (p=0.050), and sleeplessness (p=0.016). Total wellbeing was negatively associated with fatigue (OR=0.48, 95% CI 0.011-0.020)(p=0.0001). In multivariate analysis, anaemia was the most powerful independent predictor of fatigue, with OR=38.27 (95% CI 2.62-559.19)(p=0.008), followed by sleeplessness (OR=14.06 95% CI 1.44-137.02 p=0.023) and loss of appetite (OR=10.30 95% CI 1.04-101.10, p=0.045). Fatigue was unrelated to sex or age, or to the type of cancer, or the treatment category. Fatigue was common among cancer patients on palliative care. The single most powerful independent explanatory factor of fatigue was anaemia, implicating a need for interventional studies.

Mental disorders in young adulthood.

BACKGROUND: The effect of mental disorders may be particularly detrimental in early adulthood, and information on mental disorders and their correlates in this age group is important. METHOD: A questionnaire focusing on mental health was sent to a nationally representative two-stage cluster sample of 1863 Finns aged 19 to 34 years. Based on a mental health screen, all screen-positives and a random sample of screen-negatives were asked to participate in a mental health assessment, consisting of the Structured Clinical Interview for DSM-IV (SCID-I) interview and neuropsychological assessment. We also obtained case-notes from all lifetime mental health treatments. This paper presents prevalences, sociodemographic associations and treatment contacts for current and lifetime mental disorders. RESULTS: Forty percent of these young Finnish adults had at least one lifetime DSM-IV Axis I disorder, and 15% had a current disorder. The most common lifetime disorders were depressive disorders (17.7%) followed by substance abuse or dependence (14.2%) and anxiety disorders (12.6%). Of persons with any lifetime Axis I disorder, 59.2% had more than one disorder. Lower education and unemployment were strongly associated with current and lifetime disorders, particularly involving substance use. Although 58.3% of persons with a current Axis I disorder had received treatment at some point, only 24.2% had current treatment contact. However, 77.1% of persons with a current Axis I disorder who felt in need of treatment for mental health problems had current treatment contact. CONCLUSIONS: Mental disorders in young adulthood are common and often co-morbid, and they may be particularly harmful for education and employment in this age group.

Double-blind group comparative study of 2% nedocromil sodium eye drops with 2% sodium cromoglycate and placebo eye drops in the treatment of seasonal allergic conjunctivitis.

A 4 week, multicentre, double-blind, double dummy, placebo controlled group comparative study was carried out during the birch pollen season to compare the efficacy and tolerability of 2% nedocromil sodium eye drops (twice daily) and 2% sodium cromoglycate eye drops (four times daily). Participants with a history of seasonal allergic conjunctivitis (SAC) were randomized to receive nedocromil sodium (60), sodium cromoglycate (61) or placebo (64). Clinical assessment of SAC showed improvement with both active treatments compared to placebo but symptomatology was low and only changes in photophobia and grittiness reached significance (P < 0.05). Patient diaries showed significant control of itching by both active treatments, compared to placebo, with no differences between the active preparations. Patients' opinions indicated a marked placebo effect: 73% of this group reported full or moderate control of symptoms, compared with 75% in sodium cromoglycate and 80% in the nedocromil sodium group. Unusual symptoms were most common (27 patients) with nedocromil sodium eye drops: P < 0.05 vs. placebo (15 patients). There were no serious adverse events. Nedocromil sodium eye drops (b.d.) and sodium cromoglycate eye drops (q.i.d.) were both considered clinically more effective than placebo in controlling symptoms of SAC due to birch pollen.