We describe the implementation of multivariate models of familial resemblance with the Mx package. The structural equation models allow for the effects of assortative mating, additive and dominant genes, common and specific environment, and both genetic and cultural transmission between generations. Two approaches are compared: a correlational one based on Fulker and a factor model described by Phillips and Fulker. Both are illustrated by application to published data on social fears and fear of leadership measured in monozygotic and dizygotic twins and their parents. In the example data, genetic dominance yields a more parsimonious explanation of the data than does cultural transmission, although neither is needed to obtain a good fit to the data. A model of reduced genetic correlation between generations also fits the data but has inherent limitations in this sample. Extensions to sex-limitation and more complex models are discussed.
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"The correlations between genetic and environmental factors influencing alcohol intake and GGT are calculated from the genetic and environmental variances and covariances for these traits. This was done in bivariate genetic factor models (Neale et al., 1994). "
[Show abstract][Hide abstract] ABSTRACT: Blood levels of gamma-glutamyl transferase (GGT) are used as a marker for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT. However, there is variability in the response of GGT to alcohol use, which may result from genetic differences between individuals. This study aimed to determine whether the epidemiological association between alcohol intake and GGT at the population level is necessarily a causal one or may also reflect effects of genetic pleiotropy (genes influencing multiple traits).
Data on alcohol intake (grams alcohol/day) and GGT, originating from twins, their siblings and parents (N=6465) were analyzed with structural equation models. Bivariate genetic models tested whether genetic and environmental factors influencing alcohol intake and GGT correlated significantly. Significant genetic and environmental correlations are consistent with a causal model. If only the genetic correlation is significant, this is evidence for genetic pleiotropy.
Phenotypic correlations between alcohol intake and GGT were significant in men (r=.17) and women (r=.09). The genetic factors underlying alcohol intake correlated significantly with those for GGT, whereas the environmental factors were weakly correlated (explaining 4-7% vs. 1-2% of the variance in GGT respectively).
In this healthy population sample, the epidemiological association of alcohol intake with GGT is at least partly explained by genetic pleiotropy. Future longitudinal twin studies should determine whether a causal mechanism underlying this association might be confined to heavy drinking populations.
Drug and alcohol dependence 09/2013; 134(1). DOI:10.1016/j.drugalcdep.2013.09.016 · 3.42 Impact Factor
"Results of the univariate heritability study are given in Table 4. Model fit was determined using a −2 log Likelihood (−2 log L) statistic. Different nested models (AE, CE, E) were compared to the saturated ACE model based on a −2 log L difference test . The Akaike information criterion (AIC) gives a measure of model fit, taking into consideration the balance of the χ2 statistic and the number of degrees of freedom. "
[Show abstract][Hide abstract] ABSTRACT: Age-related hearing impairment (ARHI) affects 25-40% of individuals over the age of 65. Despite the high prevalence of this complex trait, ARHI is still poorly understood. We hypothesized that variance in hearing ability with age is largely determined by genetic factors. We collected audiologic data on females of Northern European ancestry and compared different audiogram representations. A web-based speech-to-noise ratio (SNR) hearing test was compared with pure-tone thresholds to see if we could determine accurately hearing ability on people at home and the genetic contribution to each trait compared. Volunteers were recruited from the TwinsUK cohort. Hearing ability was determined using pure-tone audiometry and a web-based hearing test. Different audiogram presentations were compared for age-correlation and reflection of audiogram shape. Using structural equation modelling based on the classical twin model the heritability of ARHI, as measured by the different phenotypes, was estimated and shared variance between the web-based SNR test and pure-tone audiometry determined using bivariate modelling. Pure-tone audiometric data was collected on 1033 older females (age: 41-86). 1970 volunteers (males and females, age: 18-85) participated in the SNR. In the comparison between different ARHI phenotypes the difference between the first two principle components (PC1-PC2) best represented ARHI. The SNR test showed a sensitivity and specificity of 89% and 80%, respectively, in comparison with pure-tone audiogram data. Univariate heritability estimates ranged from 0.70 (95% CI: 0.63-0.76) for (PC1-PC2) to 0.56 (95% CI: 0.48-0.63) for PC2. The genetic correlation of PC1-PC2 and SNR was -0.67 showing that the 2 traits share variances attributed to additive genetic factors. Hearing ability showed considerable heritability in our sample. We have shown that the SNR test provides a useful surrogate marker of hearing. This will enable a much larger sample to be collected at a fraction of the cost, facilitating future genetic association studies.
PLoS ONE 04/2012; 7(4):e35500. DOI:10.1371/journal.pone.0035500 · 3.23 Impact Factor
"To model phenotypic assortment, the approach described by Fulker (1982), and Neale et al. (1994) was applied which assumes spouse correlations arise through positive phenotypic assortative mating (Fig. 1b). The spouse correlation is represented in Fig. 1b by a copath (i), which represents an extrinsic correlation that influences the covariance structure of both antecedent and subsequent factors, but does not contribute to their variance (Cloninger 1980). "
[Show abstract][Hide abstract] ABSTRACT: Social isolation and loneliness in humans have been associated with physical and psychological morbidity, as well as mortality. This study aimed to assess the etiology of individual differences in feelings of loneliness. The genetic architecture of loneliness was explored in an extended twin-family design including 8,683 twins, siblings and parents from 3,911 families. In addition, 917 spouses of twins participated. The presence of assortative mating, genetic non-additivity, vertical cultural transmission, genotype-environment (GE) correlation and interaction was modeled. GE interaction was considered for several demographic characteristics. Results showed non-random mating for loneliness. We confirmed that loneliness is moderately heritable, with a significant contribution of non-additive genetic variation. There were no effects of vertical cultural transmission. With respect to demographic characteristics, results indicated that marriage, having offspring, more years of education, and a higher number of siblings are associated with lower levels of loneliness. Interestingly, these effects tended to be stronger for men than women. There was little evidence of changes in genetic architecture as a function of these characteristics. We conclude that the genetic architecture of loneliness points to non-additive genetic influences, suggesting it may be a trait that was not neutral to selection in our evolutionary past. Sociodemographic factors that influence the prevalence of loneliness do not affect its genetic architecture.