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Genetic Modelling (genetic + modelling)
Selected AbstractsInfluence of genetics on irritable bowel syndrome, gastro-oesophageal reflux and dyspepsia: a twin studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2007A. LEMBO Summary Background A genetic contribution has been proposed for irritable bowel syndrome (IBS) and gastro-oesophageal reflux disease (GERD), but is controversial. No twin data exist for dyspepsia. Aim To determine the relative contribution of genetic factors in GERD, dyspepsia (upper abdominal pain) and IBS. Methods A total of 986 twin pairs (from initial mail-out response 51%). Both members completed validated symptom and psychological questionnaires; 481 monozygotic pairs [mean (s.d.) age 53 ± 5.8 years] and 505 dizygotic pairs (mean age 54 ± 5.6 years). Results Prevalence of IBS, dyspepsia and GERD was 12%, 10% and 20%, respectively. Polychoric correlation for monozygotic twins for IBS (0.47) and GERD (0.44) were both substantially larger than those for dizygotic twins (0.17 and ,0.37, respectively). Polychoric correlation was slightly lower in monozygotic than dizygotic twins for dyspepsia. Genetic modelling confirmed the independent additive genetic effects in GERD and IBS but not dyspepsia. Estimates of genetic variance were 22% for IBS, 13% for GERD and 0% for dyspepsia, but adjusting for anxiety and depression removed the statistical significance for IBS and GERD. Conclusions There is a genetic contribution to GERD and IBS but not dyspepsia; this may be mediated by the hereditability of anxiety and depression. [source] Bladder neck mobility is a heritable traitBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 3 2005H.P. Dietz Objective Congenital connective tissue dysfunction may partly be responsible for female pelvic organ prolapse and urinary incontinence. We undertook a heritability study to determine whether mobility of the bladder neck, one of the main determinants of stress urinary incontinence, is genetically influenced. Design Heritability study using a twin model and structural equation modelling. Setting Queensland Institute of Medical Research, Brisbane, Australia. Population One hundred and seventy-eight nulliparous Caucasian female twins and their sisters (46 monozygotic pairs, 24 dizygotic pairs and 38 sisters) aged 18,24 years. Methods We performed translabial ultrasound, supine and after bladder emptying, for pelvic organ mobility. Urethral rotation and bladder neck descent were calculated using the best of three effective Valsalva manoeuvres. Main outcome measures Bladder and urethral mobility on Valsalva assessed by urethral rotation, vertical and oblique bladder neck descent. Results Genetic modelling indicated that additive genes accounted for up to 59% of the variance for bladder neck descent. All remaining variance appeared due to environmental influences unique to the individual, including measurement error. Conclusion A significant genetic contribution to the phenotype of bladder neck mobility appears likely. [source] Nonlinear epigenetic variance: review and simulationsDEVELOPMENTAL SCIENCE, Issue 1 2010Kees-Jan Kan We present a review of empirical evidence that suggests that a substantial portion of phenotypic variance is due to nonlinear (epigenetic) processes during ontogenesis. The role of such processes as a source of phenotypic variance in human behaviour genetic studies is not fully appreciated. In addition to our review, we present simulation studies of nonlinear epigenetic variance using a computational model of neuronal network development. In each simulation study, time series for monozygotic and dizygotic twins were generated and analysed using conventional behaviour genetic modelling. In the results of these analyses, the nonlinear epigenetic variance was subsumed under the non-shared environmental component. As is commonly found in behaviour genetic studies, observed heritabilities and unique environmentabilities increased with time, whereas common environmentabilities decreased. The fact that the phenotypic effects of nonlinear epigenetic processes appear as unsystematic variance in conventional twin analyses complicates the identification and quantification of the ultimate genetic and environmental causes of individual differences. We believe that nonlinear dynamical system theories provide a challenging perspective on the development of individual differences, which may enrich behaviour genetic studies. [source] The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin populationCLINICAL ENDOCRINOLOGY, Issue 6 2007Pia Skov Hansen Summary Objectives, The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size, serum levels of TSH, thyroid hormones, and thyroid antibodies in 1241 healthy Danish twin individuals and (2) assessed the contribution of the polymorphism to the trait variation and the genetic variance. Measurements, The effect of the genotype on the traits (mean ± SD) was established; associations between the TSHR-Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling. Results, The genotype distribution was Asp/Asp 84·9%; Asp/Glu 14·5% and Glu/Glu 0·6%. Carriers of the TSHR-Glu727 allele had lower TSH levels (noncarriers vs. carriers: 1·78 ± 0·93 vs. 1·60 ± 0·84 mU/l, P = 0·04). Regression analysis showed an association between the TSHR-Asp727Glu polymorphism and serum TSH (P = 0·007). The polymorphism accounted for 0·91% of the total phenotypic variance in serum TSH levels. Including the genotype in quantitative genetic modelling improved the model fit (P = 0·001); however, the genetic influence on serum TSH not attributable to this specific genetic variant was only reduced from 68·2% to 67·8%. The polymorphism was not significantly associated with thyroid size, thyroid hormones or thyroid antibody levels. Conclusions, The TSHR-727Glu allele was associated with decreasing TSH levels; however, the contribution to the genetic variance was very small. No association was found with other thyroid-related measures. [source] |