Reduction of tumor volume during radiotherapy in patients with small-cell lung cancer and its prognostic significance.

BACKGROUND: Several studies have reported the potential prognostic significance of tumor volume reduction ratio (VRR) induced by radiotherapy (RT) in patients with non-small-cell lung cancer. However, there are no data yet on the prognostic significance of volumetric shrinkage in patients with small-cell lung cancer (SCLC). This study aimed to demonstrate the correlation between tumor volume reduction ratio and treatment outcomes. MATERIALS AND METHODS: The study included 61 patients with SCLC treated with fractionated RT of the primary tumor at our institution between 2013 and 2020. The relationship between volumetric changes in gross tumor volume (GTV) during radiotherapy and outcomes were analyzed and reported. RESULTS: The median radiation dose was 59.4 Gy (median fraction dose was 1.8 Gy). The median GTV before radiotherapy was 74 cm3, with a median GTV reduction of 48%. There was a higher VRR in patients receiving concurrent radiochemotherapy (p = 0.05). No volumetric parameters were identified as relevant predictors of outcome in the entire cohort. In multivariate analysis, only age had an impact on survival, while prophylactic whole-brain radiation influenced the progression-free survival significantly. CONCLUSION: Concurrent chemotherapy was associated with a higher VRR than sequential chemotherapy. No significant impact of VRR on patients' outcome or survival was detected.

Broad and narrow environmental and genetic sources of personality differences: An extended twin family study.

OBJECTIVE: Several personality theories distinguish between rather genetically rooted, universal dispositional traits (DTs) and rather environmentally shaped, more contextualized characteristic adaptations (CAs). However, no study so far has compared different measures of theoretically postulated DTs and CAs regarding their environmental and genetic components while considering differences in measurement abstraction and reliability. This study aims to bridge this gap by testing the assumed differences in the sensitivity to environmental influences based on representative sets of DTs (Big Five and HEXACO domains and facets) and CAs (goals, interests, value priorities, religiousness, and self-schemas). METHOD: Using intra-class correlations and running extended twin family and spouses-of-twins model analyses, we analyzed a large data set (N = 1967) encompassing 636 twin pairs, 787 parent-offspring dyads, and 325 spouses/partners. RESULTS: Findings consistently support lower environmentality of DTs compared to CAs. On average, more than half of reliable variance in DTs was genetic, whereas the reverse was found for CAs. Larger environmental components in CAs were primarily attributable to larger individual-specific effects (beyond error of measurement) and factors shared by spouses. CONCLUSIONS: Findings are discussed against the background of the definitional distinction between DTs and CAs and the value of extended twin family data.

Two genetic analyses to elucidate causality between body mass index and personality.

BACKGROUND/OBJECTIVES: Many personality traits correlate with BMI, but the existence and direction of causal links between them are unclear. If personality influences BMI, knowing this causal direction could inform weight management strategies. Knowing that BMI instead influences personality would contribute to a better understanding of the mechanisms of personality development and the possible psychological effects of weight change. We tested the existence and direction of causal links between BMI and personality. SUBJECTS/METHODS: We employed two genetically informed methods. In Mendelian randomization, allele scores were calculated to summarize genetic propensity for the personality traits neuroticism, worry, and depressive affect and used to predict BMI in an independent sample (N = 3 541). Similarly, an allele score for BMI was used to predict eating-specific and domain-general phenotypic personality scores (PPSs; aggregate scores of personality traits weighted by BMI). In a direction of causation (DoC) analysis, twin data from five countries (N = 5424) were used to assess the fit of four alternative models: PPSs influencing BMI, BMI influencing PPSs, reciprocal causation, and no causation. RESULTS: In Mendelian randomization, the allele score for BMI predicted domain-general (ß = 0.05; 95% CI: 0.02, 0.08; P = 0.003) and eating-specific PPS (ß = 0.06; 95% CI: 0.03, 0.09; P < 0.001). The allele score for worry also predicted BMI (ß = -0.05; 95% CI: -0.08, -0.02; P < 0.001), while those for neuroticism and depressive affect did not (P ≥ 0.459). In DoC, BMI similarly predicted domain-general (ß = 0.21; 95% CI:, 0.18, 0.24; P < 0.001) and eating-specific personality traits (ß = 0.19; 95% CI:, 0.16, 0.22; P < 0.001), suggesting causality from BMI to personality traits. In exploratory analyses, links between BMI and domain-general personality traits appeared reciprocal for higher-weight individuals (BMI > ~25). CONCLUSIONS: Although both genetic analyses suggested an influence of BMI on personality traits, it is not yet known if weight management interventions could influence personality. Personality traits may influence BMI in turn, but effects in this direction appeared weaker.

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.

The Study of Personality Architecture and Dynamics (SPeADy): A Longitudinal and Extended Twin Family Study.

The Study of Personality Architecture and Dynamics (SPeADy) is a German research project that aims to investigate the sources of interindividual differences in intraindividual personality development. The main focus lies in the dynamic interplay between more stable core characteristics and more environmentally malleable surface characteristics, as well as between personality and life experiences over time. SPeADy includes a twin family study encompassing data from 1962 individuals (age: 14-94) of 682 families, including 570 complete twin pairs (plus 1 triplet set), 327 parents, 236 spouses and 145 children of twins. Data collection started in 2016 and data from the first wave are currently obtainable as open source. Available data comprise a broad range of personality variables, such as personality trait constructs, motives, interests, values, moral foundations, religiosity and self-related concepts. For the currently ongoing second wave of data collection, we added retrospective reports on major life events. Special features of this genetically informative study are the extended twin family data and its longitudinal design. Three assessment waves in 2 years' intervals are planned until 2022. In this article, we briefly describe the design and contents of the SPeADy twin family study as well as some recent findings, future plans and open science issues.

Genetic Variance in Homophobia: Evidence from Self- and Peer Reports.

The present twin study combined self- and peer assessments of twins' general homophobia targeting gay men in order to replicate previous behavior genetic findings across different rater perspectives and to disentangle self-rater-specific variance from common variance in self- and peer-reported homophobia (i.e., rater-consistent variance). We hypothesized rater-consistent variance in homophobia to be attributable to genetic and nonshared environmental effects, and self-rater-specific variance to be partially accounted for by genetic influences. A sample of 869 twins and 1329 peer raters completed a seven item scale containing cognitive, affective, and discriminatory homophobic tendencies. After correction for age and sex differences, we found most of the genetic contributions (62%) and significant nonshared environmental contributions (16%) to individual differences in self-reports on homophobia to be also reflected in peer-reported homophobia. A significant genetic component, however, was self-report-specific (38%), suggesting that self-assessments alone produce inflated heritability estimates to some degree. Different explanations are discussed.

Genetic and Environmental Sources of Implicit and Explicit Self-Esteem and Affect: Results from a Genetically Sensitive Multi-group Design.

In today's world, researchers frequently utilize indirect measures of implicit (i.e., automatic, spontaneous) evaluations. The results of several studies have supported the usefulness of these measures in predicting behavior, as compared to utilizing direct measures of explicit (i.e., purposeful, deliberate) evaluations. A current, under-debate issue concerns the origin of these implicit evaluations. The present genetically sensitive multi-group study analyzed data from 223 twin pairs and 222 biological core families to estimate possible genetic and environmental sources of individual differences in implicit and explicit self-esteem and affect. The results show that implicit self-esteem and affect maintain a substantial genetic basis, but demonstrate little influence from the shared environment by siblings (e.g., shared familial socialization in childhood). A bivariate analysis found that implicit and explicit evaluations of the same construct share a common genetic core which aligns with the motivation and opportunity as determinants (MODE) model.

Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts.

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.

Genetic and Environmental Parent-Child Transmission of Value Orientations: An Extended Twin Family Study.

Despite cross-cultural universality of core human values, individuals differ substantially in value priorities, whereas family members show similar priorities to some degree. The latter has often been attributed to intrafamilial socialization. The analysis of self-ratings on eight core values from 399 twin pairs (ages 7-11) and their biological parents (388 mothers, 249 fathers; ages 26-65) allowed the disentanglement of environmental from genetic transmission accounting for family resemblance in value orientations. Results indicated that parent-child similarity is primarily due to shared genetic makeup. The primary source of variance in value priorities represented environmental influences that are not shared by family members. These findings do not provide evidence for parental influences beyond genetic influences contributing to intrafamilial similarity in value priorities.

What Drives the Development of Social Inequality Over the Life Course? The German TwinLife Study.

The German twin family study 'TwinLife' was designed to enhance our understanding of the development of social inequalities over the life course. The interdisciplinary project investigates mechanisms of social inequalities across the lifespan by taking into account psychological as well as social mechanisms, and their genetic origin as well as the interaction and covariation between these factors. Main characteristics of the study are: (1) a multidimensional perspective on social inequalities, (2) the assessment of developmental trajectories in childhood, adolescence, and young adulthood in a longitudinal design by using (3) a combination of a multi-cohort cross-sequential and an extended twin family design, while (4) capturing a large variation of behavioral and environmental factors in a representative sample of about 4,000 German twin families. In the present article, we first introduce the theoretical and empirical background of the TwinLife study, and second, describe the design, content, and implementation of TwinLife. Since the data will be made available as scientific use file, we also illustrate research possibilities provided by this project to the scientific community.

The genetic and environmental roots of variance in negativity toward foreign nationals.

This study quantified genetic and environmental roots of variance in prejudice and discriminatory intent toward foreign nationals and examined potential mediators of these genetic influences: right-wing authoritarianism (RWA), social dominance orientation (SDO), and narrow-sense xenophobia (NSX). In line with the dual process motivational (DPM) model, we predicted that the two basic attitudinal and motivational orientations-RWA and SDO-would account for variance in out-group prejudice and discrimination. In line with other theories, we expected that NSX as an affective component would explain additional variance in out-group prejudice and discriminatory intent. Data from 1,397 individuals (incl. twins as well as their spouses) were analyzed. Univariate analyses of twins' and spouses' data yielded genetic (incl. contributions of assortative mating) and multiple environmental sources (i.e., social homogamy, spouse-specific, and individual-specific effects) of variance in negativity toward strangers. Multivariate analyses suggested an extension to the DPM model by including NSX in addition to RWA and SDO as predictor of prejudice and discrimination. RWA and NSX primarily mediated the genetic influences on the variance in prejudice and discriminatory intent toward foreign nationals. In sum, the findings provide the basis of a behavioral genetic framework integrating different scientific disciplines for the study of negativity toward out-groups.

Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project.

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/m2 in childhood and adolescence and up to 0.2 kg/m2 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.

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.

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.

Nuanced HEXACO: A Meta-Analysis of HEXACO Cross-Rater Agreement, Heritability, and Rank-Order Stability.

Most Five-Factor Model (FFM) questionnaire items contain unique variance that is partly heritable, stable, and consensually observable, demonstrates consistent associations with age and sex, and predicts life outcomes beyond higher order factors. Extending these findings to the HEXACO model, we meta-analyzed single-item cross-rater agreement, heritability, and 2-year stability using samples from six countries. We analyzed raw item scores and their residual variance and adjusted the estimates for measurement unreliability. The median cross-rater agreement, heritability, and stability estimates were, respectively, .30, .30, and .57, for raw items and .10, .16, and .39, for item residuals. Adjusted for reliability, the respective medians were .46 and .25 for cross-rater agreement, .46 and .39 for heritability, and .87 and .94 for stability. These results are strikingly consistent with FFM-based findings, providing nondismissible evidence that single items index a partly unique level of the trait hierarchy-personality nuances-with trait properties comparable to those of higher-order traits.

Genetic and environmental sources of individual religiousness: the roles of individual personality traits and perceived environmental religiousness.

In the current study, we examined the genetic and environmental sources of the links between individual religiousness and individual personality traits, perceived parental religiousness, and perceived peer religiousness. Data from 870 individuals (incl. 394 twin pairs) were analyzed. Variance in individual religiousness was significantly influenced by genetic effects, environmental influences shared by twins reared together, and individual-specific environmental influences. Individual religiousness showed significant associations with age, sex, specific personality traits (e.g., agreeableness, openness to values), and perceived religiousness of important social interaction partners, such as parents, best friends, and spouses. The links to personality traits were relatively small and primarily genetically mediated. The associations between individual religiousness and parental religiousness were substantial and mediated by shared environmental effects. These links significantly decreased across age accompanying a significant decrease of shared environmental influences on individual religiousness. The correlations between individual religiousness and perceived religiousness of spouses and best friends were relatively moderate but increased with age. These associations were mediated by genetic as well as nonshared environmental sources accompanying an increase of nonshared environmental influences on individual religiousness with age. The results suggest that inter-individual differences in religiousness are due to multiple sources.

The Bielefeld Longitudinal Study of Adult Twins (BiLSAT).

The Bielefeld Longitudinal Study of Adult Twins (BiLSAT) is a German longitudinal study of monozygotic and dizygotic twins reared together, including more than 1,100 twin pairs aged between 14 and 80 who participated in the first wave. Data were collected at five waves of assessment between 1993 and 2009. Initially, the study focused on genetic and environmental influences on the structure and the development in adult temperament and personality. Today, the study includes a broad range of individual variables, such as personality disorders, major life goals, interests, attitudes, values, life and work satisfaction, and major life events. A special feature of this genetically informative study lies in the multiple-rater approach (i.e., self-reports and peer reports). Longitudinal multiple-rater analyses allow researchers to go beyond the basic nature-nurture decomposition of variance in self-reports examining genetic and environmental influences on stability and change in more accurately measured individual attributes. In the current article, we briefly describe the design and contents of BiLSAT as well as some recent major findings and future plans.

Life events as environmental States and genetic traits and the role of personality: a longitudinal twin study.

The occurrence of many life events is not entirely random but genetically influenced. The current study examined the sources underlying the stability or recurrence of life events and the developmental interplay between personality traits and life events. In a longitudinal study of 338 adult twin pairs we estimated (1) the genetic and environmental sources of continuity in aggregates of life events, (2) the sources through which personality influences the experience of life events, and (3) the sources through which life events influence personality. Unlike personality which showed both genetic and environmental influences on substantial continuity over time, stability of life events was moderate and mainly influenced by genetic factors. Significant associations between personality and life events were specific to certain personality traits and qualitative aspects of life events (controllable positive, controllable negative, and less controllable negative), primarily directional from personality to life events, and basically genetically mediated. Controlled for these genetic associations, we also found some small and basically environmentally mediated effects of life events on personality traits. The results support the concept of genotype-environment correlation as a propulsive mechanism of development.

The complexity of personality: advantages of a genetically sensitive multi-group design.

Findings from many behavioral genetic studies utilizing the classical twin design suggest that genetic and non-shared environmental effects play a significant role in human personality traits. This study focuses on the methodological advantages of extending the sampling frame to include multiple dyads of relatives. We investigated the sensitivity of heritability estimates to the inclusion of sibling pairs, mother-child pairs and grandparent-grandchild pairs from the German Socio-Economic Panel Study in addition to a classical German twin sample consisting of monozygotic- and dizygotic twins. The resulting dataset contained 1.308 pairs, including 202 monozygotic and 147 dizygotic twin pairs, along with 419 sibling pairs, 438 mother-child dyads, and 102 grandparent-child dyads. This genetically sensitive multi-group design allowed the simultaneous testing of additive and non-additive genetic, common and specific environmental effects, including cultural transmission and twin-specific environmental influences. Using manifest and latent modeling of phenotypes (i.e., controlling for measurement error), we compare results from the extended sample with those from the twin sample alone and discuss implications for future research.

Genetic and environmental influences on personality profile stability: unraveling the normativeness problem.

The present study is the first to disentangle the genetic and environmental influences on personality profile stability. Spanning a period of 10 years, we analyzed the etiology of 3 aspects of profile stability (overall profile stability, distinctive profile stability, and profile normativeness) using self- and peer reports from 539 identical and 280 fraternal twins reared together. This 3-wave multirater twin design allowed us to estimate the genetic and environmental effects on latent true scores of the 3 aspects of profile stability while controlling for method effects and random error. Consistent biometric results were only found for profile normativeness, whereas overall and distinctive profile stability scores turned out to be biased. Over time, we found personality profile normativeness to be relatively stable. This stability was due to both stable genetic and nonshared environmental effects, whereas innovative variance was completely explained by nonshared environmental effects. Our findings emphasize the importance of distinguishing between the different aspects of profile stability, since overall and distinctive stability scores are likely biased due to the normativeness problem. Yet indicating a person's similarity to the average person, the normativeness of a personality profile itself has a psychological meaning beyond socially desirable responding.

A meta-analytic review of nature and nurture in religiousness across the lifespan.

Behavior genetic research yielded that affiliation to a specific religion is primarily environmental, whereas religious beliefs and practices irrespective of a specific religion have been found to be heritable to some degree. This review synthesizes the literature and provides a meta-analytic overview on all identified behavior genetic studies on religiousness since 1999. This analysis allows new insight on the nature-nurture interplay in the development of religiousness: Genetic differences in religiousness and extra-familial environmental influences increased with age, whereas shared environmental influences within families declined - in particular in the first half of life. This age trend is in line with the interpretation of an increasing importance of active gene-environment transactions and accumulating extra-familial environmental factors across the lifespan.