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

Arthur A Sas; Ahmad Vaez; Yalda Jamshidi; Ilja M Nolte; Zoha Kamali; Timothy D Spector; Harriëtte Riese; Harold Snieder

doi:10.1016/j.atherosclerosis.2017.08.008

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

Atherosclerosis. 2017 Oct:265:172-178. doi: 10.1016/j.atherosclerosis.2017.08.008. Epub 2017 Aug 31.

Authors

Arthur A Sas¹, Ahmad Vaez², Yalda Jamshidi³, Ilja M Nolte¹, Zoha Kamali⁴, Timothy D Spector⁵, Harriëtte Riese⁶, Harold Snieder⁷

Affiliations

¹ Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB, Groningen, The Netherlands.
² Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB, Groningen, The Netherlands; Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
³ Cardiogenetics Lab, Human Genetics Research Center, St. George's University of London, London SW17 0RE, United Kingdom.
⁴ Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran.
⁵ Department of Twin Research & Genetic Epidemiology, King's College, St. Thomas Campus, London SE1 7EH, United Kingdom.
⁶ Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, CC72, PO Box 30001, 9700 RB, Groningen, The Netherlands.
⁷ Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB, Groningen, The Netherlands. Electronic address: h.snieder@umcg.nl.

PMID: 28892714
DOI: 10.1016/j.atherosclerosis.2017.08.008

Abstract

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.

Keywords: Aging; C-reactive protein; Heritability; Longitudinal; Twins.

Publication types

Twin Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
C-Reactive Protein / analysis*
Female
Follow-Up Studies
Gene-Environment Interaction*
Humans
Longitudinal Studies
Middle Aged
Time Factors

Substances

C-Reactive Protein