Not really identical: Epigenetic differences in monozygotic twins and implications for twin studies in psychiatry

Haque, F. Nipa; Gottesman, Irving I.; Wong, Albert H.C.

doi:10.1002/ajmg.c.30206

Cited by 88 publications

(54 citation statements)

References 54 publications

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“…High-fat diet treatment of ApoE3L mice resulted in obesity and glucose intolerance. The variation in glucose intolerance seen in this study is typical for mouse models of diet-induced obesity (42) and likely due to epigenetic alterations as seen in monozygotic twin studies (17). This natural variation in the extent of glucose intolerance was used for correlation and regression analysis to identify biomarkers.…”

Section: Discussionmentioning

confidence: 85%

Identification of prognostic and diagnostic biomarkers of glucose intolerance in ApoE3Leiden mice

Wopereis¹,

Radonjić²,

Rubingh³

et al. 2012

Physiological Genomics

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The prevalence of diabetes mellitus Type 2 could be significantly reduced by early identification of subjects at risk, allowing for better prevention and earlier treatment. Glucose intolerance (GI) is a hallmark of the prediabetic stage. This study aims at identifying 1) prognostic biomarkers predicting the risk of developing GI later in life and 2) diagnostic biomarkers reflecting the degree of already manifest GI. To this end, disease development was followed over time in mice, and biomarkers were identified using lipidomics and transcriptomics. Young adult ApoE3Leiden mice were treated a highfat diet for 12 wk to induce GI. Blood was collected before and during disease development. The individual extent of GI was determined with a glucose tolerance test and the area under the curve (AUC) was calculated for each animal. Subject-specific AUC values were correlated to the plasma lipidome (t ϭ 0) and the white blood cell (WBC) transcriptome (t ϭ 0, 6, and 12 wk) to identify prognostic and diagnostic biomarkers, respectively. The plasma ratio of specific free fatty acids prior to high-fat feeding (C16:1/C16:0, C18:1/C18:0 and C18:2/C22:6) was significantly correlated with the AUC and predictive for future GI. Subsequently, the expression level of specific WBC genes (Acss2, Arfgap1, Tfrc, Cox6b2, Barhl2, Abcb4, Cyp4b1, Sars2, Fgf16, and Tceal8) reflected the individual degree of GI during disease progression. Specific plasma free fatty acids as well as their ratio can be used to predict future GI. The expression levels of specific WBC genes can serve as easy accessible markers to diagnose and monitor already existing GI. plasma lipidomics; white blood cell transcriptomics; diabetes mellitus Type 2; diabetes mellitus Type 2-prone transgenic ApoE3Leiden mice DIABETES MELLITUS TYPE 2 (DM2) is a metabolic disorder whose incidence has rapidly increased over the past several decades (15, 28). DM2 accounts for 90 -95% of all diagnosed cases of diabetes and is associated with a high morbidity and mortality rate (1). Glucose intolerance is an indicator of the prediabetic state and a hallmark of the disease process leading to overt DM2 (28). Glucose intolerance is a condition in which an individual has higher than normal levels of glucose in the blood upon fasting or ingestion of a glucose test solution but not high enough to be classified as DM2. This can either be due to an insufficient production of insulin or due to an inefficient response of cells to insulin (insulin resistance). In both cases, the organ uptake of glucose from the blood stream is impaired resulting in a longer residence time and elevated levels of circulating glucose. Glucose intolerance is typically diagnosed with an invasive glucose tolerance test (GTT) in which glucose is given to a subject and blood samples are taken afterward to determine how quickly it is cleared from the blood. The test is time-consuming and elaborative, and new strategies to diagnose the degree of glucose intolerance are needed. This would allow routine monitoring of disease p...

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Section: Discussionmentioning

confidence: 85%

Identification of prognostic and diagnostic biomarkers of glucose intolerance in ApoE3Leiden mice

Wopereis¹,

Radonjić²,

Rubingh³

et al. 2012

Physiological Genomics

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“…25 monozygotic twins, although genetically concordant at birth are epigenetically discordant. this fact suggests that separating nature from nurture using traditional twin studies is not as straight forward as originally proposed.…”

Section: Epigeneticsmentioning

confidence: 99%

IBS: an epigenetic perspective

Dinan

Cryan

Shanahan

et al. 2010

Nat Rev Gastroenterol Hepatol

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IBS is a common and debilitating disorder. The pathophysiology of IBS is poorly understood and is currently viewed as a biopsychosocial disorder with symptoms mediated via the brain-gut axis. Epidemiological studies of IBS point to risk factors such as familial clustering, sexual abuse and other forms of childhood trauma, low birth weight and gastrointestinal infection. Epigenetics focuses on the complex and dynamic interaction between the DNA sequence, DNA modifications and environmental factors, all of which combine to produce the phenotype. Studies in animal models of early stress and in humans who have experienced childhood trauma or abuse suggest that these events can lead to long-lasting epigenetic changes in the glucocorticoid receptor gene brought about by hypermethylation of a key regulatory component. Animal studies also indicate that the microbiota has a pivotal role in programming the core stress system, the hypothalamic-pituitary-adrenal axis and the immune system through epigenetic mechanisms. In this Perspectives, an epigenetic model of IBS is presented that incorporates many of the current findings regarding IBS, including proinflammatory markers, neuroendocrine alterations and links with both psychosocial stress and stress related to infection. We conclude that applying epigenetic methodology to this common and disabling disorder may help unravel its complex pathophysiology and lead to more effective treatments.

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“…Although the heritability of MDD is between 31-42% (Edvardsen et al, 2009;Middeldorp et al, 2005), human genomewide association studies (GWAS) have failed to demonstrate reproducible gene loci that contribute to the disease (Wray et al, 2012). Furthermore, the high discordance rate of 50% between monozygotic twins suggests factors other than genetics contribute to disease genesis (Haque et al, 2009). Environmental stressors have been identified as risk factors for depression, although individual variability in the susceptibility to adverse environmental stimuli has been reported.…”

Section: Introductionmentioning

confidence: 99%