The Heritability of Kidney Function Using an Older Australian Twin Population

Julia Jefferis; Anita Pelecanos; Vibeke Catts; Andrew Mallett

doi:10.1016/j.ekir.2022.05.012

The Heritability of Kidney Function Using an Older Australian Twin Population

Kidney Int Rep. 2022 May 18;7(8):1819-1830. doi: 10.1016/j.ekir.2022.05.012. eCollection 2022 Aug.

Authors

Julia Jefferis¹, Anita Pelecanos², Vibeke Catts³, Andrew Mallett^{4

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Affiliations

¹ Department of Renal Medicine, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
² Statistics Unit, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
³ Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁴ Institute for Molecular Bioscience and Faculty of Medicine, The University of Queensland, St Lucia, Queensland, Australia.
⁵ Department of Renal Medicine, Townsville University Hospital, Douglas, Queensland, Australia.
⁶ College of Medicine and Dentistry, James Cook University, Douglas, Queensland, Australia.

Abstract

Introduction: Twin studies are unique population models which estimate observed rather than inferred genetic components of complex traits. Nonmonogenic chronic kidney disease (CKD) is a complex disease process with strong genetic and environmental influences, amenable to twin studies. We aimed to assess the heritability of CKD using twin analysis and modeling within Older Australian Twin Study (OATS) data.

Methods: OATS had 109 dizygotic (DZ) and 126 monozygotic (MZ) twin pairs with paired serum creatinine levels. Heritability of kidney function as estimated glomerular filtration rate (eGFR CKD Epidemiology Collaboration [CKD-EPI]) was modeled using the ACE model to estimate additive heritability (A), common (C), and unique (E) environmental factors. Intratwin pair analysis using mixed effects logistic regression allowed analysis of variation in eGFR from established CKD risk factors.

Results: The median age was 69.71 (interquartile range 78.4-83.0) years, with 65% female, and a mean CKD-EPI of 82.8 ml/min (SD 6.7). The unadjusted ACE model determined kidney function to be 33% genetically determined (A), 18% shared genetic-environmental (C), and 49% because of unique environment (E). This remained unchanged when adjusted for age, hypertension, and sex. Hypertension was associated with eGFR; however, intertwin variance in hypertension did not explain variance in eGFR. Two or more hypertension medications were associated with decreased eGFR (P = 0.009).

Conclusion: This study estimates observed heritability at 33%, notably higher than inferred heritability in genome-wide association study (GWAS) (7.1%-18%). Epigenetics and other genomic phenomena may explain this heritability gap. Difference in antihypertension medications explains part of unique environmental exposures, though discordance in hypertension and diabetes does not.

Keywords: eGFR; heritability; kidney function; twin study.