M J Galsworthy

Sex differences in early verbal and non‐verbal cognitive development

The present study of over 3000 2-year-old twin pairs used a sex-limitation model to examine genetic and environmental origins of sex differences in verbal and non-verbal cognitive ability. Girls scored significantly higher on both measures (p<0.0001), although gender only accounted for approximately 3% of the variance in verbal ability and 1% of the variance in non-verbal cognitive ability. For the verbal measure boys showed greater heritability than girls. Also the twin-pair correlation is significantly lower for opposite-sex twins than for non-identical same-sex twins. This indicates that individual differences in verbal ability include some sex-specific factors. Non-verbal cognitive ability did not differ in aetiology for boys and girls. We conclude that genetic and environmental influences differ for girls and boys for early verbal but not non-verbal development.

Evidence for general cognitive ability (g) in heterogeneous stock mice and an analysis of potential confounds

The heterogeneous stock (HS) is a genetically outbred line of mice established more than 30 years ago from an 8‐way cross of C57BL/6, BALB/c, RIII, AKR, DBA/2, I, A/J and C3H inbred mouse strains. The present study compared the performance of 40 HS mice across a battery of diverse cognitive tasks under a variety of motivations. Indices of emotionality were also included in order to assess their influence on performance. All measures of ability loaded positively on an unrotated first principal component that accounted for 31% of the variance, suggesting the presence of a common factor of general cognitive ability (g) underlying all tasks. A first factor derived from anxiety indices correlated nonsignificantly with all cognitive tasks and nonsignificantly with this g factor, supporting the hypothesis that the factor is cognitive rather than temperamental in nature. The factor was also robust in relation to outliers and sex differences, accounting for 28% of the variance after removal of outlier individuals and also after correcting for variance owing to sex differences. A general cognitive ability (g) appears to underlie the performance of HS mice on a battery tapping diverse cognitive demands.

X inactivation as a source of behavioural differences in monozygotic female twins

Although members of monozygotic twin pairs are identical in genome sequence, they may differ in patterns of gene expression. One early and irreversible process affecting gene expression, which can create differences within pairs of female monozygotic twins, is X inactivation - one twin can express mainly paternally-received genes on the X chromosome while the other twin expresses mainly maternally-received genes. It follows that non-identical X chromosome expression may cause female monozygotic twins to correlate less strongly than male monozygotic twins on complex behavioural traits affected by X-linked loci. We tested this hypothesis using data from around 4000 same-sex twin pairs on 9 social, behavioural and cognitive measures at ages 2, 3 and 4. Consistent with our hypothesis, monozygotic males were generally more similar than monozygotic females. Three of four significant differences were in traits showing higher correlations in males than females, and these traits - prosocial behaviour, peer problems, and verbal ability - have all been proposed previously in the literature as being influenced by genes on the X chromosome. Interestingly, dizygotic twins showed the reverse pattern of correlations for similar variables, which is also consistent with the X inactivation hypothesis; taken together, then, our monozygotic and dizygotic results suggest the presence of quantitative trait loci on the X chromosome.

Home-cage activity in heterogeneous stock (HS) mice as a model of baseline activity.

Behavioral genetic work in humans indicates that clinical hyperactivity is best viewed as the extreme end of activity levels in the population. However, current animal models of hyperactivity are not studied as quantitative traits as they are either knockout models or inbred strains. Furthermore, these animal models generally demonstrate elevated locomotion in novel environments, but not in their home‐cages. This is the opposite of the symptoms seen in the human condition where childhood hyperactivity is generally more pronounced in constant, unstimulating situations. In this study we filmed an outbred population of 44 heterogeneous stock (HS) mice under red light during their active phase, to assess the reliability of individual differences in home‐cage behavior and extract an index of home‐cage activity (HCA) level. We then compared this measure to locomotor behavior in a novel environment — the open‐field. Reliable individual differences in home‐cage behaviors such as running, swinging on bars, and burrowing were found, and principal component factor analysis yielded a general activity factor, which accounted for 32% of the variance and correlated 0.90 with a subjective impression of activity level. The correlation between HCA and locomotor activity in the open‐field was 0.23, which was non‐significant. However, the association with HCA level appeared to increase over the five minutes of the open‐field, presumably as the mice habituated. Furthermore, although mice displaying particularly high and low HCA were indistinguishable early in the open‐field task, they became significantly differentiated over time. We conclude that home‐cage behaviors and the open‐field, after habituation, display good face and construct validity, and may provide a good model of baseline activity for quantitative trait loci (QTL) discovery and functional genomics in the HS mice.

Genetic and gender influences on nocturnal bladder control : A study of 2900 3-year-old twin pairs

OBJECTIVE The present study of over 2900 twin pairs born in England and Wales in 1994 examines the influences of genetics and gender on nocturnal bladder control at 3 years of age. MATERIALS AND METHOD Parent report data was analysed in terms of means and components of variance, using a sex-limitation model to explore genetic and environmental variation within and between the sexes. RESULTS Both genetics and gender are seen to influence acquisition: bladder control at 3 years is moderately heritable (24%), and girls show on average slightly increased acquisition compared with boys, even within opposite-sex pairs. The sex-limitation modelling showed an interaction between genetic influence and gender whereby nocturnal bladder control was significantly more heritable in boys (33%) than girls (10%). CONCLUSIONS Both genetics and gender are important and interacting factors in the aetiology of nocturnal bladder control.Objective: The present study of over 2900 twin pairs born in England and Wales in 1994 examines the influences of genetics and gender on nocturnal bladder control at 3 years of age. Materials and Method: Parent report data was analysed in terms of means and components of variance, using a sex-limitation model to explore genetic and environmental variation within and between the sexes. Results: Both genetics and gender are seen to influence acquisition: bladder control at 3 years is moderately heritable (24%), and girls show on average slightly increased acquisition compared with boys, even within opposite-sex pairs. The sexlimitation modelling showed an interaction between genetic influence and gender whereby nocturnal bladder control was significantly more heritable in boys (33%) than girls (10%). Conclusions: Both genetics and gender are important and interacting factors in the aetiology of nocturnal bladder control.