Phenotypic, Genetic and Environmental Architecture of the Components of Sleep Quality.

The genetic and environmental underpinnings of sleep quality have been widely investigated. However, less is known about the etiology of the different sleep quality components and their associations. Subjective sleep quality has been studied most commonly using the Pittsburgh Sleep Quality Index (PSQI). Therefore, this work aimed to study the structure of sleep quality dimensions in a population-based twin sample by examining the etiology of the associations among the PSQI components themselves and between them. The sample comprised 2129 participants from the Murcia Twin Registry. In order to study the phenotypic, genetic and environmental structure of the PSQI we used three alternative multivariate twin models including all seven sub-scales of the PSQI (subjective sleep quality, latency, duration, efficiency, disturbances, use of sleeping medication and daytime dysfunction): a multivariate model (with seven separate correlated factors), a common pathway model and an independent pathway model. The multivariate correlated factors model showed the best fit to the data. All twin models indicated significant genetic overlap among most of the PSQI components, except daytime dysfunction and use of sleep medication. Bivariate heritability explained between 25 and 50% of the covariance for most associations between dimensions. Furthermore, the common pathway model showed that around one third of the variance (0.32; CI 95% 0.18.0.43) of a latent factor common to all questionnaire dimensions is explained by genetic factors. Genetic influences on a latent factor common to all questionnaire dimensions produced the same heritability estimates as the PSQI global score. However, sleep quality dimensions showed considerable specificity regarding its genetic-environmental structure.

Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts.

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.

Educational attainment of same-sex and opposite-sex dizygotic twins: An individual-level pooled study of 19 twin cohorts.

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 (ß = -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 (ß = 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.

Genetic and environmental variation in educational attainment: an individual-based analysis of 28 twin cohorts.

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.

An Update of Twin Research in Spain: The Murcia Twin Registry.

The Murcia Twin Registry (MTR) is the only population-based registry in Spain. Created in 2006, the registry has been growing more than a decade to become one of the references for twin research in the Mediterranean region. The MTR database currently comprises 3545 adult participants born between 1940 and 1977. It also holds a recently launched satellite registry of university students (N = 204). Along five waves of data collection, the registry has gathered questionnaire and anthropometric data, as well as biological samples. The MTR keeps its main research focus on health and health-related behaviors from a public health perspective. This includes lifestyle, health promotion, quality of life or environmental conditions. Future short-term development points to the expansion of the biobank and the continuation of the collection of longitudinal data.

Association of current and former smoking with body mass index: A study of smoking discordant twin pairs from 21 twin cohorts.

BACKGROUND: Smokers tend to weigh less than never smokers, while successful quitting leads to an increase in body weight. Because smokers and non-smokers may differ in genetic and environmental family background, we analysed data from twin pairs in which the co-twins differed by their smoking behaviour to evaluate if the association between smoking and body mass index (BMI) remains after controlling for family background. METHODS AND FINDINGS: The international CODATwins database includes information on smoking and BMI measured between 1960 and 2012 from 156,593 twin individuals 18-69 years of age. Individual-based data (230,378 measurements) and data of smoking discordant twin pairs (altogether 30,014 pairwise measurements, 36% from monozygotic [MZ] pairs) were analysed with linear fixed-effects regression models by 10-year periods. In MZ pairs, the smoking co-twin had, on average, 0.57 kg/m2 lower BMI in men (95% confidence interval (CI): 0.49, 0.70) and 0.65 kg/m2 lower BMI in women (95% CI: 0.52, 0.79) than the never smoking co-twin. Former smokers had 0.70 kg/m2 higher BMI among men (95% CI: 0.63, 0.78) and 0.62 kg/m2 higher BMI among women (95% CI: 0.51, 0.73) than their currently smoking MZ co-twins. Little difference in BMI was observed when comparing former smoking co-twins with their never smoking MZ co-twins (0.13 kg/m2, 95% CI 0.04, 0.23 among men; -0.04 kg/m2, 95% CI -0.16, 0.09 among women). The associations were similar within dizygotic pairs and when analysing twins as individuals. The observed series of cross-sectional associations were independent of sex, age, and measurement decade. CONCLUSIONS: Smoking is associated with lower BMI and smoking cessation with higher BMI. However, the net effect of smoking and subsequent cessation on weight development appears to be minimal, i.e. never more than an average of 0.7 kg/m2.

Heritability of sleep quality in a middle-aged twin sample from Spain.

Study Objectives: Sleep quality is associated with health throughout the life span, which is particularly salient in middle-age and older adulthood. Sleep quality appears to be influenced by both genetic and environmental factors. However, there is still limited information about genetic influences on sleep quality in middle-aged adults, and particularly in those from certain geographical locations. We estimated the magnitude of genetic and environmental influences on sleep quality in a representative sample of middle-aged Spanish twins. Methods: The sample comprised 2150 individuals born between 1939 and 1966, who participate in the Murcia Twin Registry. To estimate the heritability of sleep quality variables, we performed univariate analyses for the global score on the Pittsburgh sleep quality index and for each of its components. Results: We found moderate but significant heritability (34%) for sleep quality. The genetic variance of the components of the Pittsburgh index ranged from 30 to 45 per cent, except for sleep efficiency for which no genetic influence could be detected. In summary, there was a moderate genetic influence on most dimensions of sleep quality in a sample of adult male and female twins. Shared environment influences were not found. Conclusions: This study adds new information regarding the underlying determinants of sleep quality by providing heritability estimates in a middle-aged population-based representative sample from a geographical location that has not been included in studies of this type previously. This could provide a reference point for future research regarding sleep research in middle-age.

[The Murcia Twin Registry. A resource for research on health-related behaviour]. / El Registro de Gemelos de Murcia. Un recurso para la investigación sobre conductas relacionadas con la salud.

Genetically informative designs and, in particular, twin studies, are the most widely used methodology to analyse the relative contribution of genetic and environmental factors to inter-individual variability. These studies basically compare the degree of phenotypical similarity between monozygotic and dizygotic twin pairs. In addition to the traditional estimate of heritability, this kind of registry enables a wide variety of analyses which are unique due to the characteristics of the sample. The Murcia Twin Registry is population-based and focused on the analysis of health-related behaviour. The observed prevalence of health problems is comparable to that of other regional and national reference samples, which guarantees its representativeness. Overall, the characteristics of the Registry facilitate developing various types of research as well as genetically informative designs, and collaboration with different initiatives and consortia.

Altruistic Behavior among Twins : Willingness to Fight and Self-Sacrifice for Their Closest Relatives.

According to kin selection theory, indirect reproductive advantages may induce individuals to care for others with whom they share genes by common descent, and the amount of care, including self-sacrifice, will increase with the proportion of genes shared. Twins represent a natural situation in which this hypothesis can be tested. Twin pairs experience the same early environment because they were born and raised at the same time and in the same family but their genetic relatedness differs depending on zygosity. We compared the degree of willingness to fight and sacrifice for the co-twin among monozygotic (MZ) and dizygotic (DZ) pairs in a sample of 1443 same-sex and opposite-sex twins. We also analyzed the effect of the subject's gender and that of the co-twin on those altruistic behaviors. Results partly supported the postulated explanation. MZ twins (who share nearly their entire genome) were significantly more likely than DZ twins (who on average share half of their segregating genes) to self-sacrifice for their co-twins, but zygosity did not affect willingness to fight for him/her. The genders of the subject and of the co-twin, not genetic relatedness, were the best predictors of aggressive altruistic intentions.

Effects of Social Attitude Change on Smoking Heritability.

Societal attitudes and norms to female smoking changed in Spain in the mid-twentieth century from a restrictive to a tolerant, and an even pro-smoking, posture, while social attitudes remained stable for males. We explored whether this difference in gender-related social norms influenced the heritability of two tobacco use measures: lifetime smoking and number of years smoking. We used a population-based sample of 2285 twins (mean age = 55.78; SD = 7.45; 58% females) whose adolescence began between the mid-1950s and the early 1980s. After modeling the effect of sex and year of birth on the variance components, we observed that the impact of the genetic and shared environmental factors varied differently by birth cohort between males and females. For females, shared environment explained a higher proportion of variance than the genetic factors in older cohorts. However, this situation was inverted in the younger female cohorts. In contrast, no birth cohort effect was observed for males, where the impact of the genetic and environmental factors remained constant throughout the study period. These results suggest that heritability is larger in a permissive social environment, whereas shared-environmental factors are more relevant in a society that is less tolerant to smoking.

Correction to: Altruistic Behavior among Twins : Willingness to Fight and Self-Sacrifice for Their Closest Relatives.

The original version of this article unfortunately contained a mistake. The presentation of the article title and subtitle was incorrect.

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.

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.

Association between birthweight and later body mass index: an individual-based pooled analysis of 27 twin cohorts participating in the CODATwins project.

Background: There is evidence that birthweight is positively associated with body mass index (BMI) in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. We analysed the association between birthweight and BMI from infancy to adulthood within twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 27 twin cohorts in 17 countries. The pooled data included 78 642 twin individuals (20 635 monozygotic and 18 686 same-sex dizygotic twin pairs) with information on birthweight and a total of 214 930 BMI measurements at ages ranging from 1 to 49 years. The association between birthweight and BMI was analysed at both the individual and within-pair levels using linear regression analyses. Results: At the individual level, a 1-kg increase in birthweight was linearly associated with up to 0.9 kg/m2 higher BMI (P < 0.001). Within twin pairs, regression coefficients were generally greater (up to 1.2 kg/m2 per kg birthweight, P < 0.001) than those from the individual-level analyses. Intra-pair associations between birthweight and later BMI were similar in both zygosity groups and sexes and were lower in adulthood. Conclusions: These findings indicate that environmental factors unique to each individual have an important role in the positive association between birthweight and later BMI, at least until young adulthood.

Does Familial Aggregation of Chronic Low Back Pain Affect Recovery?: A Population-Based Twin Study.

STUDY DESIGN: Longitudinal twin-cohort study. OBJECTIVE: To investigate the effect familial aggregation of chronic low back pain (LBP) has on the recovery from chronic LBP. SUMMARY OF BACKGROUND DATA: LBP is a worldwide problem, with pain and disability often becoming chronic. Genetics and familial behaviors could significantly affect the recovery from chronic LBP but have not been extensively investigated. METHODS: A total of 624 Spanish twins from the Murcia Twin Registry reported experiencing chronic LBP within the past 2 years during the 2009/11 data collection wave and were followed up in 2013. Familial aggregation of chronic LBP was determined by the co-twin experiencing chronic LBP within the past 2 years at baseline. Twins reporting LBP "within the past 4 weeks" at follow-up were considered to have not recovered. RESULTS: There were 455 twins with available data on LBP at follow-up and available data on LBP from their co-twin at baseline. Twins with an affected co-twin at baseline were significantly more likely to have not recovered from chronic LBP at follow-up (odds ratio [OR] = 1.6, 95% confidence interval [CI]: 1.0-2.4, P = 0.046). This relationship was stronger for monozygotic twins (OR = 2.5, 95% CI: 1.3-4.8, P = 0.006) (n = 172) but disappeared when considering only dizygotic twins (OR = 1.1, 95% CI: 0.6-2.0, P = 0.668) (n = 283). Sibling-relative recurrence risk (λ s) was 1.2 for the total sample, 1.5 for monozygotic twins, and 1.1 for dizygotic twins. CONCLUSION: Having a sibling with chronic LBP at baseline increased the likelihood of LBP at follow-up by 20%, with this likelihood increasing to 50% if the sibling was an identical twin. These results are novel and highlight the important influence genetics have on people's recovery from chronic LBP. Information regarding the presence of chronic LBP within a family is easy to obtain and has the potential to inform clinicians on which patients are less likely to recover when treatment implementation is not considered. LEVEL OF EVIDENCE: 3.

Age and gender effects on the prevalence of poor sleep quality in the adult population.

OBJECTIVE: Sleep quality has a significant impact on health and quality of life and is affected, among other factors, by age and sex. However, the prevalence of problems in this area in the general population is not well known. Therefore, our objective was to study the prevalence and main characteristics of sleep quality in an adult population sample. METHODS: 2,144 subjects aged between 43 and 71 years belonging to the Murcia (Spain) Twin Registry. Sleep quality was measured by self-report through the Pittsburgh Sleep Quality Index (PSQI). Logistic regression models were used to analyse the results. RESULTS: The prevalence of poor sleep quality stands at 38.2%. Univariate logistic regression analyses showed that women were almost twice as likely as men (OR: 1.88; 95% confidence interval [95%CI]: 1.54 to 2.28) to have poor quality of sleep. Age was directly and significantly associated with a low quality of sleep (OR: 1.05; 95%CI: 1.03 to 1.06). CONCLUSIONS: The prevalence of poor sleep quality is high among adults, especially women. There is a direct relationship between age and deterioration in the quality of sleep. This relationship also appears to be more consistent in women.

Does educational attainment increase the risk of low back pain when genetics are considered? A population-based study of Spanish twins.

BACKGROUND CONTEXT: There is limited research investigating educational attainment as a risk factor for low back pain (LBP), with the influence of gender commonly being neglected. Furthermore, genetics and early shared environment explain a substantial proportion of LBP cases and need to be controlled for when investigating risk factors for LBP. PURPOSE: To investigate whether educational attainment affects the prevalence and risk of LBP differently in men and women while controlling for the influence of genetics and early shared environment. STUDY DESIGN: This is a cross-sectional and prospective twin case-control study. PATIENT SAMPLE: Adult monozygotic (MZ) and dizygotic (DZ) twins from the Murcia Twin Registry, with available data on educational attainment, formed the base sample for this study. The prevalence analysis considered twins with available data on LBP in 2013 (n=1,580). The longitudinal analysis considered twins free of LBP at baseline (2009-2011), with available data on LBP at follow-up (2013) (n=1,077). OUTCOME MEASURES: Data on the lifetime prevalence of activity limiting LBP (outcome) and educational attainment (risk factor) were self-reported. METHODS: The prevalence analysis investigated the cross-sectional association between educational attainment and LBP, whereas the longitudinal analysis investigated whether educational attainment increased the risk of developing LBP. Both analyses were performed in the following sequence. First, a total sample analysis was performed on all twins (considering them as individuals), adjusting for confounding variables selected by the data. Second, to control for the influence of genetics and early shared environment, a within-pair case-control analysis (stratified by zygosity) was performed on complete twin pairs discordant for LBP (ie, one twin had LBP, whereas the co-twin did not). All analyses were stratified for gender where possible, with an interaction term determining whether gender was a significant moderator of the association between educational attainment and LBP. RESULTS: Women with either general secondary or university education were less likely to experience (prevalence analysis) or to develop LBP (longitudinal analysis). Educational attainment did not affect the risk of LBP in men. When controlling for the effects of genetics and early shared environment, the relationship between educational status and LBP in women was no longer statistically significant. CONCLUSIONS: Educational attainment affects LBP differently in men and women, with higher levels of education only decreasing the risk of developing LBP in women. After adjusting for genetics and early shared environment, the relationship between educational attainment and LBP in women disappears. This suggests that genetics and early shared environment are confounding the relationship between educational attainment and LBP in women.

Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994.

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.

Is Chronic Low Back Pain Associated with the Prevalence of Coronary Heart Disease when Genetic Susceptibility Is Considered? A Co-Twin Control Study of Spanish Twins.

OBJECTIVE: To investigate the chronic low back pain and coronary heart disease relationship, after adjusting for relevant confounders, including genetics. METHODS: In a cross-sectional design, 2148 twins were recruited from the Murcia Twin Registry, Spain. The exposure was chronic LBP and the outcomes were myocardial infarction and other coronary heart diseases-lifetime and in the last 2 years-based on standardized health-related questionnaires. First, logistic regression analysis investigated associations of the total sample followed by a matched co-twin control analyses, with all complete twin pairs discordant for chronic LBP utilised, separated for zygosity-dizygotic (DZ) and monozygotic (MZ) pairs, which adjusted for shared familial factors, including genetics. RESULTS: Chronic LBP pain is associated with lifetime myocardial infarction [odds ratio (OR) = 2.69, 95% confidence interval (CI) = 1.35-5.36], other coronary heart diseases over a lifetime (OR = 2.58, 95% CI: 1.69-3.93) and in the last two years (OR = 2.19, 95% CI: 1.33-3.60), while there was a borderline association with myocardial infarction in the last 2 years (OR = 2.64, 95% CI: 0.98-7.12). Although the magnitude of the association remained or increased in the co-twin control analyses, none reached statistical significance. CONCLUSION: Chronic LBP is associated with a higher prevalence of myocardial infarction and coronary heart disease. It is possible that this association remains even when controlling for genetics and early shared environment, although this should be investigated with larger samples of twins discordant for LBP.

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.