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1.
  • Silventoinen, K., et al. (författare)
  • The CODATwins Project : The current status and recent findings of COllaborative Project of Development of Anthropometrical Measures in Twins
  • 2019
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 22:6, s. 800-808
  • Tidskriftsartikel (refereegranskat)abstract
    • 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. 
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  • Silventoinen, K., et al. (författare)
  • Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region : An individual-based pooled analysis of 40 twin cohorts
  • 2017
  • Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 106:2, s. 457-466
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m2)], but factors modifying these variance components are poorly understood.Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity.Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs).Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI.Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.
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  • Jelenkovic, A., et al. (författare)
  • Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994
  • 2016
  • Ingår i: eLIFE. - Cambridge, United Kingdom : eLife Sciences Publications. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.
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  • Jelenkovic, Aline, et al. (författare)
  • Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
  • 2015
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
  • Tidskriftsartikel (refereegranskat)abstract
    • A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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  • Silventoinen, Karri, et al. (författare)
  • The CODATwins Project : The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
  • 2015
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:4
  • Tidskriftsartikel (refereegranskat)abstract
    • For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
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  • Silventoinen, K., et al. (författare)
  • Educational attainment of same-sex and opposite-sex dizygotic twins : An individual-level pooled study of 19 twin cohorts
  • 2021
  • Ingår i: Hormones and Behavior. - : Elsevier. - 0018-506X .- 1095-6867. ; 136
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers.
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  • Silventoinen, Karri, et al. (författare)
  • Education in twins and their parents across birth cohorts over 100 years : an individual-level pooled analysis of 42 twin cohorts
  • 2017
  • Ingår i: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
  • Tidskriftsartikel (refereegranskat)abstract
    • Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
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  • Silventoinen, Karri, et al. (författare)
  • Genetic and environmental variation in educational attainment : an individual-based analysis of 28 twin cohorts
  • 2020
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.
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17.
  • Tikhonoff, V., et al. (författare)
  • Symptoms of anxiety and depression across adulthood and blood pressure in late middle age: the 1946 British birth cohort
  • 2014
  • Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 32:8, s. 1590-1599
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Previous studies testing the hypothesis that symptoms of anxiety and depression increase blood pressure (BP) levels show inconsistent and limited findings. We examined the association between those symptoms across adult life and BP in late middle age. Methods: Using data from 1683 participants from the MRC NSHD, we investigated associations between affective symptoms at ages 36, 43, 53 and 60-64 years and SBP and DBP at age 60-64. Multivariable linear regression was used to examine the effect on BP of affective symptoms at each age separately and as a categorical cumulative score based on the number of times an individual was classified as a 'case'. Models were adjusted for sex, BMI, educational attainment, socioeconomic position, heart rate, lifestyle factors and antihypertensive treatment. Results: In fully adjusted models, we observed lower SBP in study members with case-level symptoms at one to two time-points [-1.83mmHg; 95% confidence interval (CI) -3.74 to 0.01] and at three to four time-points (-3.93 mmHg; 95% CI -7.19 to -0.68) compared with those never meeting case criteria suggesting a cumulative inverse impact of affective symptoms on SBP across adulthood (P value for trend 0.022). Sex and BMI had a large impact on the estimates while not other confounders. Potential mediators such as heart rate and lifestyle behaviours had a little impact on the association. SBP at age 36 and behavioural changes across adulthood, as additional covariates, had a little impact on the association. A similar but weaker trend was observed for DBP. Conclusion: A cumulative effect of symptoms of anxiety and depression across adulthood results in lower SBP in late middle age that is not explained by lifestyle factors and antihypertensive treatment. Mechanisms by which mood may impact BP should be investigated.
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  • Dregan, A, et al. (författare)
  • Common mental disorders within chronic inflammatory disorders: a primary care database prospective investigation
  • 2019
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:5, s. 688-695
  • Tidskriftsartikel (refereegranskat)abstract
    • There is inconsistent evidence about the association between inflammatory disorders and depression and anxiety onset in a primary care context. The study aimed to evaluate the risk of depression and anxiety within multisystem and organ-specific inflammatory disorders.MethodsThis is a prospective cohort study with primary care patients from the UK Clinical Practice Research Datalink diagnosed with an inflammatory disorder between 1 January 2001 and 31 December 2016. These patients were matched on age, gender, practice and index date with patients without an inflammatory disorder. The study exposures were seven chronic inflammatory disorders. Clinical diagnosis of depression and anxiety represented the outcome measures of interest.ResultsAmong 538 707 participants, the incidence of depression ranged from 14 per 1000 person-years (severe psoriasis) to 9 per 1000 person-years (systemic vasculitis), substantively higher compared with their comparison group (5–7 per 1000 person-years). HRs of multiple depression and anxiety events were 16% higher within inflammatory disorders (HR, 1.16, 95% CI 1.12 to 1.21, p<0.001) compared with the matched comparison group. The incidence of depression and anxiety was strongly associated with the age at inflammatory disorder onset. The overall HR estimate for depression was 1.90 (95% CI 1.66 to 2.17, p<0.001) within early-onset disorder (<40 years of age) and 0.93 (95% CI 0.90 to 1.09, p=0.80) within late-onset disorder (≥60 years of age).ConclusionsPrimary care patients with inflammatory disorders have elevated rates of depression and anxiety incidence, particularly those patients with early-onset inflammatory disorders. This finding may reflect the impact of the underlying disease on patients’ quality of life, although the precise mechanisms require further investigation.
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  • Harber-Aschan, Lisa, 1987-, et al. (författare)
  • Cardiometabolic risk profiles in a Sri Lankan twin and singleton sample
  • 2022
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionPrevention of cardiovascular disease and diabetes is a priority in low- and middle-income countries, especially in South Asia where these are leading causes of morbidity and mortality. The metabolic syndrome is a tool to identify cardiometabolic risk, but the validity of the metabolic syndrome as a clinical construct is debated. This study tested the existence of the metabolic syndrome, explored alternative cardiometabolic risk characterisations, and examined genetic and environmental factors in a South Asian population sample.MethodsData came from the Colombo Twin and Singleton follow-up Study, which recruited twins and singletons in Colombo, Sri Lanka, in 2012–2015 (n = 3476). Latent class analysis tested the clustering of metabolic syndrome indicators (waist circumference, high-density lipoprotein cholesterol, triglycerides, blood pressure, fasting plasma glucose, medications, and diabetes). Regression analyses tested cross-sectional associations between the identified latent cardiometabolic classes and sociodemographic covariates and health behaviours. Structural equation modelling estimated genetic and environmental contributions to cardiometabolic risk profiles. All analyses were stratified by sex (n = 1509 men, n = 1967 women).ResultsThree classes were identified in men: 1) “Healthy” (52.3%), 2) “Central obesity, high triglycerides, high fasting plasma glucose” (40.2%), and 3) “Central obesity, high triglycerides, diabetes” (7.6%). Four classes were identified in women: 1) “Healthy” (53.2%), 2) “Very high central obesity, low high-density lipoprotein cholesterol, raised fasting plasma glucose” (32.8%), 3) “Very high central obesity, diabetes” (7.2%) and 4) “Central obesity, hypertension, raised fasting plasma glucose” (6.8%). Older age in men and women, and high socioeconomic status in men, was associated with cardiometabolic risk classes, compared to the “Healthy” classes. In men, individual differences in cardiometabolic class membership were due to environmental effects. In women, genetic differences predicted class membership.ConclusionThe findings did not support the metabolic syndrome construct. Instead, distinct clinical profiles were identified for men and women, suggesting different aetiological pathways.
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24.
  • Holmes, Emily A., et al. (författare)
  • Multidisciplinary research priorities for the COVID-19 pandemic : a call for action for mental health science
  • 2020
  • Ingår i: Lancet psychiatry. - 2215-0374 .- 2215-0366. ; 7:6, s. 547-560
  • Tidskriftsartikel (refereegranskat)abstract
    • The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries.
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  • Tikhonoff, Valérie, et al. (författare)
  • The relationship between affective symptoms and hypertension-role of the labelling effect: the 1946 British birth cohort.
  • 2016
  • Ingår i: Open heart. - : BMJ. - 2053-3624. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the association between repeated measures of affective symptoms collected over 2 decades and hypertension (clinically ascertained or self-report); to test whether, among people with hypertension, affective symptoms are associated with awareness of hypertension, and to evaluate the longitudinal effects of the label of hypertension on affective symptoms.Multivariable logistic regression, accounting for confounders and mediators, were used to test the aforementioned associations in 1683 participants from a national British cohort.Weak evidence of a cumulative impact of affective symptoms across adulthood on self-reported hypertension at age 60-64years was observed (OR 1.40 (95% CI 1.10 to 1.78) and 1.19 (0.79 to 1.80) for symptoms at 1-2 time points and at 3-4 time points vs no symptoms, respectively). Study members with affective symptoms in recent times were more likely to have self-reported hypertension at age 60-64years than those without symptoms (OR 1.47 (1.10 to 1.96)). Similar results were observed for awareness of hypertension (OR 2.00 (1.30 to 3.06)). Conversely, no associations were found with clinically ascertained hypertension. The act of labelling someone as hypertensive at age 53years was associated with affective symptoms at age 60-64years, independently of antihypertensive treatment and affective symptoms at the time of the diagnosis (OR 2.40 (1.32 to 4.36)).Our findings suggest that elevated risk of hypertension in participants with affective symptoms might be explained by awareness of hypertension and by exposure to medical attention, though not by a direct effect of affective symptoms on blood pressure. Conversely, long-term psychological consequences of the label of hypertension are observed.
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  • Velupillai, Sumithra, et al. (författare)
  • Risk Assessment Tools and Data-Driven Approaches for Predicting and Preventing Suicidal Behavior
  • 2019
  • Ingår i: Frontiers in Psychiatry. - : FRONTIERS MEDIA SA. - 1664-0640. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Risk assessment of suicidal behavior is a time-consuming but notoriously inaccurate activity for mental health services globally. In the last 50 years a large number of tools have been designed for suicide risk assessment, and tested in a wide variety of populations, but studies show that these tools suffer from low positive predictive values. More recently, advances in research fields such as machine learning and natural language processing applied on large datasets have shown promising results for health care, and may enable an important shift in advancing precision medicine. In this conceptual review, we discuss established risk assessment tools and examples of novel data-driven approaches that have been used for identification of suicidal behavior and risk. We provide a perspective on the strengths and weaknesses of these applications to mental health-related data, and suggest research directions to enable improvement in clinical practice.
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