Heritability Estimates from Twin Studies. I. Formulae of Heritability Estimates

Kang, Kw Kang Kae Won; Christian, J. C.; Norton, Ja Norton Ja

doi:10.1017/s000156600000948x

Cited by 48 publications

(19 citation statements)

References 11 publications

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“…26 The heritability of the well-established heritable traits, BMI (63%), height (96%), and weight (97%) in our study subjects are concordant with reported values 14,15 providing confidence that our study population is informative with respect to estimates of heritability. NH = not heritable.…”

Section: Figuresupporting

confidence: 87%

The heritability of hemolysis in stored human red blood cells

et al. 2015

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Background The transfusion of red blood cells (RBCs) with maximum therapeutic efficacy is a major goal in transfusion medicine. One of the criteria used in determining stored RBC quality is end of storage hemolysis. Between donors, a wide range of hemolysis is observed under identical storage conditions. Here, a potential mechanism for this wide range is investigated. We hypothesize that the magnitude of hemolysis is a heritable trait. Also, we investigated correlations between hemolysis and RBC metabolites; this will establish pathways influencing hemolysis as future targets for genetic analysis. Study Design and Methods Units of RBCs from identical and non-identical twins were collected and stored under standard conditions for 56 days. Hemolysis, ATP, and total glutathione were measured throughout storage. Non-targeted metabolic analyses were performed on RBCs that had been stored for 28 days. Heritability was determined by comparing values between identical and non-identical twins. Results Hemolysis was found to be heritable (mean >45 %) throughout the storage period. Correlations were observed between hemolysis and metabolites from the amino acid, sugar, and purine metabolism, lipid metabolism and transport, and glycolysis pathways. Three metabolites also exhibited heritability (> 20%). No correlation was found with ATP or total glutathione. Conclusion The susceptibility of RBCs to lysis during storage is partly determined by inheritance. We have also uncovered several pathways that are candidate targets for future genome wide association studies. These findings will aid in the design of better storage solutions and the development of donor screening tools that minimize hemolysis during storage.

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Section: Figuresupporting

confidence: 87%

The heritability of hemolysis in stored human red blood cells

et al. 2015

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“…The mean of the ICC values of MZ and DZ twin populations were used to estimate the heritability of changes in analyte levels during storage. Heritability estimates were calculated using the method derived by Newman et al ., h 2 = (ICC mz − ICC DZ ) / (1 − ICC DZ )[36]. …”

Section: Methodsmentioning

confidence: 99%

“…Heritability was estimated using the method of Newman et al from the mean intra-class correlation coefficients [36]. The estimated overall (population) heritability for all time points for GSH is 79%, for GSSG 60%, for tGSH 67%, and for E hc 75%.…”

Section: Figurementioning

confidence: 99%

Heritability of glutathione and related metabolites in stored red blood cells

Erve

Doskey

Wagner

et al. 2014

Free Radical Biology and Medicine

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Red blood cells (RBCs) collected for transfusion deteriorate during storage. This deterioration is termed the “RBC storage lesion”. There is increasing concern over the safety, therapeutic efficacy, and toxicity of transfusing longer-stored units of blood. The severity of the RBC storage lesion is dependent on storage-time and varies markedly between individuals. Oxidative damage is considered a significant factor in development of the RBC storage lesion. In this study, the variability during storage and heritability of antioxidants and metabolites central to RBC integrity and function were investigated. In a classic twin study, we determined the heritability of glutathione (GSH), glutathione disulfide (GSSG), the status of the GSSG, 2H+/2GSH couple (Ehc) and total glutathione (tGSH) in donated RBCs over 56 days of storage. Intracellular GSH and GSSG concentrations both decrease during storage (median net loss of 0.52 ± 0.63 mM (median ± SD) and 0.032 ± 0.107mM, respectively over 42 days). Taking into account the decline in pH, Ehc became more positive (oxidized) during storage (median net increase of 35 ± 16 mV). In our study population heritability estimates for GSH, GSSG, tGSH, and Ehc measured over 56 days of storage are 79%, 60%, 67%, and, 75% respectively. We conclude that susceptibility of stored RBCs to oxidative injury due to variations in the GSH-redox buffer are highly variable among individual donors and strongly heritable. Identifying the genes that regulate the storage-related changes in this redox buffer could lead to the development of new methods to minimize the RBC storage lesion.

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“…With the ICC values for MZ and DZ twins for a given trait, the proportion of the observable inter-individual variation attributed to genotypic differences ( i.e. heritability) can be estimated [24]. …”

Section: Introductionmentioning

confidence: 99%

The concentration of glutathione in human erythrocytes is a heritable trait

Erve

Wagner

Ryckman

et al. 2013

Free Radical Biology and Medicine

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Glutathione (GSH) is a ubiquitous, redox active, small molecule that is critical to cellular and organism health. In red blood cells (RBCs), the influence of the environment (e.g. diet and lifestyle) on GSH levels has been demonstrated in numerous studies. However, it remains unknown if levels of GSH are determined principally by environmental factors, or if there is a genetic component, i.e. heritability. To investigate this we conducted a twin study. Twin studies are performed by comparing the similarity in phenotypes between mono- and di-zygotic twin pairs. We determined the heritability of GSH, as well as its oxidation product glutathione disulfide (GSSG), the sum of GSH equivalents (tGSH), and the status of the GSSG/2GSH couple (marker of oxidation status, Ehc) in RBCs. In our study population we found that the estimated heritability for the intracellular concentration of GSH in RBCs is 57 %; GSSG is 51 %, tGSH is 63 %, and Ehc is 70 %. We conclude that a major portion of the phenotype of these traits is controlled genetically. We anticipate that these heritabilities will also be reflected in other cell types. The discovery that genetics play a major role in the innate levels of redox active species in RBCs is paradigm-shifting and opens new avenues of research in the field of redox biology. Inherited RBC anti-oxidant levels may be important disease modifiers. By identifying the relative contributions of genes and the environment to anti-oxidant variation between individuals, new therapeutic strategies can be developed. Understanding the genetic determinants of these inherited traits may allow personalized approaches to relevant therapies.

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Heritability Estimates from Twin Studies. I. Formulae of Heritability Estimates

Abstract: Over the past 50 years a large number of methods have been proposed for estimating heritability from twin studies. The present paper describes the most commonly cited of these estimates as a first step in evaluating their usefulness. A critical review will then follow.

Cited by 48 publications

References 11 publications

The heritability of hemolysis in stored human red blood cells

The heritability of hemolysis in stored human red blood cells

Heritability of glutathione and related metabolites in stored red blood cells

The concentration of glutathione in human erythrocytes is a heritable trait

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