Bivariate genetic modelling of the response to an oral glucose tolerance challenge: A gene x environment interaction approach

AIMS/HYPOTHESIS: Twin and family studies have shown the importance of genetic factors influencing fasting and 2 h glucose and insulin levels. However, the genetics of the physiological response to a glucose load has not been thoroughly investigated. METHODS: We studied 580 monozygotic and 1,937 dizygotic British female twins from the Twins UK Registry. The effects of genetic and environmental factors on fasting and 2 h glucose and insulin levels were estimated using univariate genetic modelling. Bivariate model fitting was used to investigate the glucose and insulin responses to a glucose load, i.e. an OGTT. RESULTS: The genetic effect on fasting and 2 h glucose and insulin levels ranged between 40% and 56% after adjustment for age and BMI. Exposure to a glucose load resulted in the emergence of novel genetic effects on 2 h glucose independent of the fasting level, accounting for about 55% of its heritability. For 2 h insulin, the effect of the same genes that already influenced fasting insulin was amplified by about 30%. CONCLUSIONS/INTERPRETATION: Exposure to a glucose challenge uncovers new genetic variance for glucose and amplifies the effects of genes that already influence the fasting insulin level. Finding the genes acting on 2 h glucose independently of fasting glucose may offer new aetiological insight into the risk of cardiovascular events and death from all causes

Критична рефлексія української античності: етапи та тенденції (Ukrainian antiquity in critical reflection: stages and tendencies)

У статті окреслюються основні етапи критичної рецепції вітчизняним літературознавством ХХ – початку ХХІ ст. явищ українсько-античного діалогу. Визначається зміст й особливості кожного: активна критична рецепція в контексті обґрунтування ідей європеїзму на першому етапі; спад критичної рефлексії й поодинокі дослідження в материковій Україні й переміщення центру аналітики в діаспору на другому етапі; певна реконструкція знань про українську античність разом із деконструкцією радянської ідеології – повернення до естетичних засад наукового аналізу української античності упродовж третього етапу; поліметодологічність«античних» студій, посилення уваги до типологічних узагальнень, актуалізація інтертекстуальних досліджень на четвертому етапі. (The article analyzes critical reception by the Ukrainian literature study of 20th – 21st centuries of the phenomena of Ukrainian-Antique dialogue. The terminological definitions’ diapason of the phenomenon of perception of antiquity as an intertext is analyzed. At the same time it is noted that in the twentieth century the history of scientific reflection of Ukrainian antiquity illustrated general trends of literature study perception of such issues: the classical heritage, its meaning and role in the contemporary literary process; peculiarities of mythopoetics; the study of intertextual relations; the specifics of interpretation of works with intellectual dominant and so on. Stages of «Antique» studies are defined, the content and features of each are determined. Active and critical reception of Ukrainian antiquity in the context of justification of the ideas of Europeanism and definition of cultural and aesthetic reference points in the first stage (1920s); the decline of critical reflection and singular studies in mainland Ukraine and movement of the center of «Antique» studies into Ukrainian diaspora literature in the second stage (from 1928 to the end of 1950s); reconstruction of some knowledge of Ukrainian antiquity (1990s in particular) with deconstruction of Soviet ideology – a return to the aesthetic principles of scientific analysis of Ukrainian antiquity during the third stage (1950 – 1990s); polymethodology of «Antique» studies, increased attention to typological generalizations of artistic phenomena, actualization of intertextual studies in fourth stage (the last decade of the twentieth century and until now).

Interaction between the MTHFR C677T polymorphism and traumatic childhood events predicts depression

Childhood trauma is associated with the onset and recurrence of major depressive disorder (MDD). The thermolabile T variant of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) is associated with a limited (oxidative) stress defense. Therefore, C677T MTHFR could be a potential predictor for depressive symptomatology and MDD recurrence in the context of traumatic stress during early life. We investigated the interaction between the C677T MTHFR variant and exposure to traumatic childhood events (TCEs) on MDD recurrence during a 5.5-year follow-up in a discovery sample of 124 patients with recurrent MDD and, in an independent replication sample, on depressive syniptomatology in 665 healthy individuals from the general population. In the discovery sample, Cox regression analysis revealed a significant interaction between MTHFR genotype and TCEs on MOD recurrence (P = 0.017). Over the 5.5-year follow-up period, median time to recurrence was 191 days for T-allele carrying patients who experienced TCEs (T + and TCE +); 461 days for T - and TCE + patients; 773 days for T + and TCE - patients and 866 days for T - and TCE - patients. In the replication sample, a significant interaction was present between the MTHFR genotype and TCEs on depressive symptomatology (P = 0.002). Our results show that the effects of TCEs on the prospectively assessed recurrence of MOD and self-reported depressive symptoms in the general population depend on the MTHFR genotype. In conclusion, T-allele carriers may be at an increased risk for depressive symptoms or MOD recurrence after exposure to childhood trauma

Familial Aggregation of CKD and Heritability of Kidney Biomarkers in the General Population:The Lifelines Cohort Study

Rationale & Objective: Chronic kidney disease (CKD) has a heritable component. We aimed to quantify familial aggregation of CKD in the general population and assess the extent to which kidney traits could be explained by genetic and environmental factors. Study Design: Cross-sectional 3-generation family study. Setting & Participants: Data were collected at entry into the Lifelines Cohort Study from a sample of the general population of the northern Netherlands, composed predominantly of individuals of European ancestry. Exposure: Family history of CKD. Outcomes: The primary outcome was CKD, defined as estimated glomerular filtration rate (eGFR) Analytical Approach: Familial aggregation of CKD was assessed by calculating the recurrence risk ratio (RRR), using adapted Cox proportional hazards models. Heritability of continuous kidney-related traits was estimated using linear mixed models and defined as the ratio of the additive genetic variance to total phenotypic variance. All models were adjusted for age, sex, and known risk factors for kidney disease. Results: Among 155,911 participants with available eGFR data, the prevalence of CKD was 1.19% (1,862 cases per 155,911). The risk of CKD in those with an affected first-degree relative was 3 times higher than the risk in the total sample ( RRR, 3.04 [95% CI, 2.26-4.09). In those with an affected spouse, risk of CKD was also higher (RRR, 1.56 [95% CI, 1.20-1.96]), indicative of shared environmental factors and/or assortative mating. Heritability estimates of eGFR, UAE, and UACR were 44%, 20%, and 18%, respectively. For serum urea, creatinine, and uric acid, estimates were 31%, 37%, and 48%, respectively, whereas estimates for serum electrolytes ranged from 22% to 28%. Limitations: Use of estimated rather than measured GFR. UAE data only available in a subsample. Conclusions: In this large population-based family study, a positive family history was strongly associated with increased risk of CKD. We observed moderate to high heritability of kidney traits and related biomarkers. These results indicate an important role of genetic factors in CKD risk