J JEFFERIS1, V CATTS2, A MALLETT1,3
1Department of Renal Medicine, Royal Brisbane and Women’s Hospital, Herston, Australia, 2Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, 3Institute for Molecular Bioscience and Faculty of Medicine, The University of Queensland, , St Lucia, Australia
Aim: Older Australian Twin Registry (OATS) data was modelled to assess the heritability of Chronic Kidney Disease (CKD) using twin analysis.
Background: Twin studies are unique population models which estimate the observed rather than inferred genetic component of complex traits. Non-monogenic CKD is a complex, polygenic disease process with strong genetic and environmental influences, amenable to twin studies.
Methods: 109 dizygotic twin pairs and 126 monozygotic twin pairs with serum creatinine data were analysed. Heritability of kidney function (eGFR CKD-EPI), was modelled using the ACE model to estimate additive heritability (A), common (C) and unique (E) environmental factors. Intra-twin pair analysis used mixed model logistic regression to analyse variation in eGFR from established CKD risk factors.
Results: The median age was 69.71 years, 65% female and median CKD-EPI of 82.96mL/min. Average blood pressure was 132/78. The ACE model determined variance in kidney function was attributable to 37% additive genetic factors (A), 13% shared environmental (C) and 49% due to unique environmental factors (E). This remained unchanged when adjusted for age, diabetes, hypertension and gender.
The unique environmental factors (E) were analysed using intra-twin variation. In preliminary analysis discordant numbers of anti-hypertensive agents were associated with difference in eGFR.
Conclusions: In the Genone Wide Association Study (GWAS) era, twin studies are a powerful tool to functionally understand genetic and environmental interplay in human disease. This study estimates observed heritability at 37%, which is notably higher than inferred heritability in GWAS studies (7.1-18%). Epigenetics may explain the heritability gap. Difference in anti-hypertension medications may account for some of the environmental variation, interestingly discordance in hypertension and diabetes did not.
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