Genetic Architecture of the Pro-Inflammatory State in an Extended Twin-Family Design

Abstract

In this study we examined the genetic architecture of variation in the pro-inflammatory state, using an extended twin-family design. Within the Netherlands Twin Register Biobank, fasting Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), C-Reactive Protein (CRP), and fibrinogen levels were available for 3,534 twins, 1,568 of their non-twin siblings, and 2,227 parents from 3,095 families. Heritability analyses took into account the effects of current and recent illness, anti-inflammatory medication, female sex hormone status, age, sex, body mass index, smoking status, month of data collection, and batch processing. Moderate broad-sense heritability was found for all inflammatory parameters (39%, 21%, 45%, and 46% for TNF-α, IL-6, CRP and fibrinogen, respectively). For all parameters, the remaining variance was explained by unique environmental influences and not by environment shared by family members. There was no resemblance between spouses for any of the inflammatory parameters, except for fibrinogen. Also, there was no evidence for twin-specific effects. A considerable part of genetic variation was explained by non-additive genetic effects for TNF-α, CRP, and fibrinogen. For IL-6, all genetic variance was additive. This study may have implications for future genome-wide association studies by setting a clear numerical target for genome-wide screens that aim to find genetic variants regulating the levels of these pro-inflammatory markers.

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

“…The longitudinal design, with the long follow-up time of up to 10 years, and the relatively large sample size provided more statistical power and methodological opportunities compared to previous smaller, crosssectional studies. We did not find evidence for genetic dominance, however, in contrast to some previous cross-sectional twin studies that also had large sample sizes [37,39].…”

On the Estimation of Heritability with Family-Based and Population-Based Samples

“…cannot easily handle MZ twins, and a single individual for each MZ twin was randomly selected for analysis with both ASSOC and GCTA. There is other software available that can handle MZ twins [ 15 – 17 ] in pedigrees, but this was not considered because the number of genotyped MZ twins is very small and so the variance attributable to common environment could not be well estimated in these cohorts using the GRM. We used the program PEDINFO in S.A.G.E.…”

Causes of Variation in The Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratios: a Twin-Family Study

“…The plasma subsamples were snap-frozen and stored at -30°C. One heparin plasma subsample was used to determine CRP by the 1000 CRP assay (Diagnostic Product Corporation, CA, USA) [32].…”