Behavioural laterality refers to a consistent asymmetry in skill or preference between the hands, feet or eyes, and is related to lateralization of functions, such as language, within the brain. However, while lateralization varies between individuals both in terms of direction and degree, the aetiology of these traits is still poorly understood. The aim of this thesis was to investigate the aetiology of behavioural laterality with a genetic epidemiological framework.
The data considered in this thesis were collected from twins and their siblings during studies conducted by the Queensland Institute of Medical Research (Australia) and collaborators at Curing University (Australia), University of Adelaide (Australia) and the Free University of Amsterdam (The Netherlands). The combined data sample included data from 444,832 individuals from 21, 153 families. Writing hand data were available fro the entire sample, and throwing hand data were available for almost 18,000 families. Annett Handedness Classification, Ambiguity, Footedness, and Eye-dominance data were available for subsections of the sample. Year of birth within the sample ranged from 1900 to 2000.
Sex, age (as quantified by year of birth), and birth-weight effects were found on the distributions of the handedness measures, and corrections were applied accordingly. No zygosity or twinning effects were observed on the distributions. In addition, No differences were observed between the co-twin correlations of same-sex and opposite-sex dizygotic twins, or between twin-siblings and dizygotic twin-twin correlations, suggesting that twinning per se did not influence behavioural laterality. Similarly, no evidence of mirror imaging was found and prevalence of left-side preference and co-twin correlations did not differ between mono-chorionic and di-chorionic monozygotic twins, even after allowing for inaccuracy within the placentation reports.
Heritabilities of the laterality phenotypes were assessed using the extended twin family design in which the phenotypic variance is partitioned in to that due to genetic (additive or dominant) and environmental (common and unique effects. Across measures the majority of variance (70-90%) was due to unique environmental influences. However, significant additive genetic influences were found on the writing hand (19.9%0 and throwing hand (31.7%) measures. In addition, significant genotype-environment iterations were found with age (year of birth) and birth-weight, such that the influence of additive genetic effects was larger in later born participants and in those with heavier birth weights.
Multivariate analyses revealed that the majority of covariation between handedness measures, and between hand, foot and eye dominance was due to shared unique environmental influences. However, a common environmental factor was shared by throwing hand, footedness and eye dominance, and significant genetic covariation was present between the ambiguity score and footedness, suggesting some familial effects are common across the different behavioural lateralities.
The covariation of hand, foot and eye dominance, with personality, cognition asthma and sexual orientation were examined. After correcting for multiple testing, the most interesting finding were a relationship between the ambiguity score (which counts the number of either responses on a handedness questionnaire) and performance IQ measures. Individuals with higher ambiguity scores attained higher scores on performance IQ tests, including object assembly and spatial relations. Bivariate analyses showed these relationships were primarily due to shared genetic effects.
Linkage analyses were undertaken with a sub-sample of 715 families to locate quantitative trait loci influencing behavioural laterality. Two suggestive regions were identified one on chromosome 10 the other on 19. Simulation of empirical p-values supported the suggestive coincident linkage for writing, throwing and footedness on chromosome 19 could also be considered suggestive (p=.004).
There was no evidence for X-chromosome linkage in this sample, but length of the CAG repeat sequence of the Androgen receptor (Xq11-12) was found to predict handedness. This association was found in two independent samples of women and one sample of men, such that the likelihood of left handedness increased in those individuals with variants of the androgen receptor associated with lower testosterone levels. Considered together, these results will contribute to the slowly growing number of genotypic studies of human laterality, suggesting a range of candidate genes that may be pursed.