The relationship between neuroticism and inflammatory markers: a twin study.

INTRODUCTION: Neuroticism is an important marker of vulnerability for both mental and physical disorders. Its link with multiple etiological pathways has been studied before. Inflammatory markers have been demonstrated to predict similar mental and physical disorders as neuroticism. However, currently no study has focused on the shared genetic background of neuroticism and inflammatory markers. In the present study we will focus on the phenotypic and genetic relationship between neuroticism and three commonly used inflammatory markers: C-reactive protein (CRP), fibrinogen and Immunoglobulin-G (IgG). MATERIAL AND METHODS: The study was conducted in 125 Dutch female twin pairs. For each participant, four different neuroticism scores were available to calculate a neuroticism composite score that was used in the statistical analyses. Blood samples for inflammatory marker determination were taken after an overnight fast. Heritabilities, phenotypic and genetic correlations were estimated using bivariate structural equation modeling. RESULTS: Heritabilities are fair for neuroticism (0.55), CRP (0.52) and fibrinogen (0.67) and moderate for IgG (0.43). No significant phenotypic or genetic correlations were found between neuroticism and the inflammatory markers. Interaction models yielded no moderation of the genetic and environmental pathways in the regulation of inflammatory markers by neuroticism. CONCLUSION: Substantial heritabilities were observed for all variables. No evidence was found for significant shared (or moderation of) genetic or environmental pathways underlying neuroticism and inflammatory status.

The age-dependency of genetic and environmental influences on serum cytokine levels: a twin study.

UNLABELLED: Previous epidemiologic studies have evaluated the use of immunological markers as possible tools for measuring ageing and predicting age-related pathology. The importance of both genetic and environmental influences in regulation of these markers has been emphasized. In order to further evaluate this relationship, the present study aims to investigate the relative influence of genetic and environmental factors on four key cytokines involved in the human immune response (Interleukin (IL)-1ß, IL-6, IL-10 and Tumor Necrosis Factor (TNF)-α). In addition, the role of age as a possible moderator on these influences was evaluated. METHODS: The study was conducted in 1603 females from the Twins UK registry, with mean age ± SD of 60.4 ± 12.2 years, including 863 monozygotic twins (385 pairs and 93 singletons) and 740 dizygotic twins (321 pairs and 98 singletons). Heritability was estimated using structural equation modeling. The role of age as a moderator was evaluated using gene-age interaction models. RESULTS: Heritabilities were moderate for IL-1ß (range: 0.27-0.32) and IL-10 (0.30) and low for IL-6 (range: 0.15-0.16) and TNF-α (range: 0.17-0.23). For IL-1ß, heritability declines with age due to an increase in unique environmental factors. For TNF-α, heritability increases with age due to a decrease in unique environmental factors. CONCLUSION: The current findings illustrate the importance of genetic and environmental influences on four cytokines involved in the human immune response. For two of these there is evidence that heritability changes with age owing to changes in environmental factors unique to the individual.

Genetic and environmental influences on stability and change in baseline levels of C-reactive protein: A longitudinal twin study.

BACKGROUND AND AIMS: Cross-sectional twin and family studies report a moderate heritability of baseline levels of C-reactive protein (CRP), ranging from 0.10 to 0.65 for different age ranges. Here, we investigated the stability and relative impact of genetic and environmental factors underlying serum levels of CRP, using a longitudinal classical twin design. METHODS: A maximum of 6201 female twins from the TwinsUK registry with up to three CRP measurements (i.e. visit 1 [V1], visit 2 [V2] and visit 3 [V3]) over a 10-year follow-up period were included in this study. Structural equation modeling was applied to dissect the observed phenotypic variance into its genetic and environmental components. To estimate the heritability of CRP as well as its genetic and environmental correlations across different time points, a trivariate model was used. RESULTS: Natural log (ln) CRP levels significantly increased from V1 to V2 (p=4.4 × 10-25) and between V1 and V3 (p=1.2 × 10-15), but not between V2 and V3. The median (IQR) follow-up time between V1 and V3 was 9.58 (8.00-10.46) years. Heritability estimates for CRP were around 50% and constant over time (0.46-0.52). Additionally, adjustment for BMI did not meaningfully change the heritability estimates (0.49-0.51). The genetic correlations between visits were significantly smaller than one, ranging from 0.66 to 0.85. CONCLUSIONS: The present study provides evidence for stable heritability estimates of CRP of around 50% with advancing age. However, between-visit genetic correlations are significantly lower than 1, indicating emergence of new genetic effects on CRP levels with age.

Gompertz' survivorship law as an intrinsic principle of aging.

We defend the hypothesis that life-spanning population survivorship curves, as described by Gompertz' law and composed from cross-sectional data (here mortality), reflect an intrinsic aging principle active in each subject of that population. In other words Gompertz' law reflects aging of a prototypical subject, provided minimal (or no) external causes of death (i.e. fatal infections, starvation, accidents). Our approach deviates from the traditional (exponential) Gompertz' hazard function. For instance, the here formulated Gompertz' law accurately describes old-age deceleration of both all-cause mortality and the incidence of some ageing-associated cancers, as illustrated for the Dutch population. We consider the possibility that the old-age expression and progression of cancer and other pathologies becomes suppressed, because of random (and exponential) accumulation of damage during life. Gompertz' law may trigger new concepts and models describing life-spanning physiological and pathological processes of aging. We discuss (and reject) various aging models (e.g. a predominant role of individual variations at birth; reliability theory) and point to the explanatory potential of network models and systemic regulatory models.