The Heritability of Kidney Function Using an Older Australian Twin Population

Jefferis, Julia, Pelecanos, Anita, Catts, Vibeke, and Mallett, Andrew (2022) The Heritability of Kidney Function Using an Older Australian Twin Population. Kidney International Reports, 7 (8). pp. 1819-1830.

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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.

Item ID: 76109
Item Type: Article (Research - C1)
ISSN: 2468-0249
Keywords: eGFR, heritability, kidney function, twin study
Copyright Information: © 2022 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Funders: National Health and Medical Research Council (NHMRC), Australian Research Council (ARC)
Projects and Grants: ARC 401162, NHMRC 1024224, NHMRC 1025243, NHMRC 1045325, NHMRC 1085606, NHMRC 568969, NHMRC 1093083, NHMRC 1079102
Date Deposited: 28 Sep 2022 07:34
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320214 Nephrology and urology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 50%
20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 50%
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