Is any but a tiny fraction of handedness variance likely to be due to the external environment

Abstract: Around the world, about 10% people prefer using their left-hand. What leads to this fixed proportion across populations and what determines left versus right preference at an individual level is far from being established. Genetic studies are a tool to answer these questions. Analysis in twins and family show that about 25% of handedness variance is due to genetics. In spite of very large cohorts, only a small fraction of this genetic component can be pinpoint to specific genes. Some of the genetic associations identified so far provide evidence for shared biology contributing to both handedness and cerebral asymmetries. In addition, they demonstrate that handedness is a highly polygenic trait. Typically, handedness is measured as the preferred hand for writing. This is a very convenient measure, especially to reach large sample sizes, but quantitative measures might capture different handedness dimensions and be better suited for genetic analyses. This paper reviews the latest findings from molecular genetic studies as well as the implications of using different ways of assessing handedness.

Abstract: Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We re-sampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers and right-handers showed average differences of surface area asymmetry within fusiform, anterior insular, anterior-middle-cingulate and precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins: TUBB, TUBA1B, TUBB3, TUBB4A, MAP2 and NME7 – the latter is mutated in left-right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in left-handedness: on the postcentral gyrus and inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas non-heritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference.

Abstract: Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We resampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers compared to right-handers showed average differences of surface area asymmetry within the fusiform cortex, the anterior insula, the anterior middle cingulate cortex, and the precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins: TUBB, TUBA1B, TUBB3, TUBB4A, MAP2, and NME7-mutations in the latter can cause left to right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in left-handedness: on the postcentral gyrus and the inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas nonheritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference.

Abstract: Asymmetries in the functional and structural organization of the nervous system are widespread in the animal kingdom and especially characterize the human brain. Although there is little doubt that asymmetries arise through genetic and nongenetic factors, an overarching model to explain the development of functional lateralization patterns is still lacking. Current genetic psychology collects data on genes relevant to brain lateralizations, while animal research provides information on the cellular mechanisms mediating the effects of not only genetic but also environmental factors. This review combines data from human and animal research (especially on birds) and outlines a multi-level model for asymmetry formation. The relative impact of genetic and nongenetic factors varies between different developmental phases and neuronal structures. The basic lateralized organization of a brain is already established through genetically controlled embryonic events. During ongoing development, hemispheric specialization increases for specific functions and subsystems interact to shape the final functional organization of a brain. In particular, these developmental steps are influenced by environmental experiences, which regulate the fine-tuning of neural networks via processes that are referred to as ontogenetic plasticity. The plastic potential of the nervous system could be decisive for the evolutionary success of lateralized brains.

Abstract: Psychopathy has historically been conceptualized as a mental disorder, but there is growing evidence that it may instead be an alternative, adaptive life history strategy designed by natural selection. Although the etiology of mental disorders is not fully understood, one likely contributor is perturbations affecting neurodevelopment. Nonright-handedness is a sign of such perturbations, and therefore can be used to test these competing models. If psychopathy is a mental disorder, psychopaths should show elevated rates of nonright-handedness. However, an adaptive strategy perspective expects psychopaths to be neurologically healthy and therefore predicts typical rates of nonright-handedness. We meta-analyzed 16 studies that investigated the association between psychopathy and handedness in various populations. There was no difference in the rates of nonright-handedness between community participants high and low in psychopathy. Furthermore, there was no difference between psychopathic and nonpsychopathic offenders in rates of nonright-handedness, though there was a tendency for offenders scoring higher on the Interpersonal/Affective dimension of psychopathy to have lower rates of nonright-handedness, and for offenders scoring higher on the Behavioral dimension of psychopathy to have higher rates of nonright-handedness. Lastly, there was no difference in rates of nonright-handedness between psychopathic and nonpsychopathic mental health patients. Thus, our results fail to support the mental disorder model and partly support the adaptive strategy model. We discuss limitations of the meta-analysis and implications for theories of the origins of psychopathy.

Abstract: Polycyclic aromatic compounds (PACs) are known due to their mutagenic activity. Among them, 2-nitrobenzanthrone (2-NBA) and 3-nitrobenzanthrone (3-NBA) are considered as two of the most potent mutagens found in atmospheric particles. In the present study 2-NBA, 3-NBA and selected PAHs and Nitro-PAHs were determined in fine particle samples (PM 2.5) collected in a bus station and an outdoor site. The fuel used by buses was a diesel-biodiesel (96:4) blend and light-duty vehicles run with any ethanol-to-gasoline proportion. The concentrations of 2-NBA and 3-NBA were, on average, under 14.8 µg g−1 and 4.39 µg g−1, respectively. In order to access the main sources and formation routes of these compounds, we performed ternary correlations and multivariate statistical analyses. The main sources for the studied compounds in the bus station were diesel/biodiesel exhaust followed by floor resuspension. In the coastal site, vehicular emission, photochemical formation and wood combustion were the main sources for 2-NBA and 3-NBA as well as the other PACs. Incremental lifetime cancer risk (ILCR) were calculated for both places, which presented low values, showing low cancer risk incidence although the ILCR values for the bus station were around 2.5 times higher than the ILCR from the coastal site.

Abstract: Four different descriptions of lateral asymmetry are reviewed and their probable interrelations examined. Two main features are distinguished: first, a normal distribution of relative efficiency of the two sides which probably applies to all species subject to lateral differences; second, a factor specific to humans which induces a shift of the normal distribution toward dextrality. A brief discussion of the origins of asymmetry leads to the conclusion that the basic normal distribution probably depends on accidental variation while the human shift to the right may be a product of both cultural and genetic influences. The latter could imply that human right handedness is inherited while left handedness is not.

Abstract: Handedness refers to a consistent asymmetry in skill or preferential use between the hands and is related to lateralization within the brain of other functions such as language. Previous twin studies of handedness have yielded inconsistent results resulting from a general lack of statistical power to find significant effects. Here we present analyses from a large international collaborative study of handedness (assessed by writing/drawing or self report) in Australian and Dutch twins and their siblings (54,270 individuals from 25,732 families). Maximum likelihood analyses incorporating the effects of known covariates (sex, year of birth and birth weight) revealed no evidence of hormonal transfer, mirror imaging or twin specific effects. There were also no differences in prevalence between zygosity groups or between twins and their singleton siblings. Consistent with previous meta-analyses, additive genetic effects accounted for about a quarter (23.64%) of the variance (95%CI 20.17, 27.09%) with the remainder accounted for by non-shared environmental influences. The implications of these findings for handedness both as a primary phenotype and as a covariate in linkage and association analyses are discussed.

Abstract: The importance of non-shared environment lay hidden within quantitative genetic studies since they began nearly a century ago. Quantitative genetic methods, such as twin and adoption methods, were designed to tease apart nature and nurture in order to explain family resemblance. For nearly all complex phenotypes, it has emerged that the answer to the question of the origins of family resemblance is nature—things run in families primarily for genetic reasons. However, the best available evidence for the importance of environmental influence comes from this same quantitative genetic research because genetic influence never explains all of the variance for complex phenotypes, and the remaining variance must be ascribed to environmental influences. Yet it took many decades for the full meaning of these findings to emerge. If genetics explains why siblings growing up in the same family are similar, but the environment is important, then it must be the case that the salient environmental effects do not make siblings similar. That is, they are not shared by children growing up in the same family—they must be ‘non-shared’. This implication about non-shared environmental import lay fallow in the field of quantitative genetics because the field’s attention was then firmly on the nature–nurture debate. ‘Nurture’ in the nature–nurture debate was implicitly taken to mean shared environment because from Freud onwards, theories of socialization had assumed that children’s environments are doled out on a family-by-family basis. In contrast, the point of non-shared environment is that environments are doled out on a child-by-child basis. Note that the phrase ‘non-shared environment’ is shorthand for a component of phenotypic variance—it refers to ‘effects’ rather than ‘events’, as discussed later. The 1987 paper reprinted in this issue of the International Journal of Epidemiology1 brought together evidence for the importance of non-shared environment in the development of personality, psychopathology and cognitive abilities, expanding on a previous paper.2 The purpose of the present commentary is to reflect on non-shared environment three decades after the topic emerged. Progress and problems in studying non-shared environment were reviewed in 2001;3 rather than providing a systematic update of this burgeoning field, my current goal is to suggest some new directions for research in this area. The 1987 paper was published with 32 commentaries and our response,4 which I recommend. These commentaries and the response to them raised many of the issues that resurfaced during the following decades, such as the following: Non-shared environmental effects need to be distinguished from error of measurement (yes). Non-additive genetic variance can account for non-shared environmental effects (no). Genotype–environment interaction and correlation can account for non-shared environmental effects (no). Prenatal factors can contribute to non-shared environmental effects (yes). Non-shared environmental effects may be more influential in extreme situations such as abusive families (yes). Perceptions of environment can be an important source of non-shared experience (yes). Non-shared environment can involve chance in the sense of idiosyncratic experiences (yes). It is noteworthy that none of the 1987 commentaries disagreed with the fundamental phenomenon that children growing up in the same family are very different. There was also general agreement that most of the environmental variance is of the non-shared variety. As I reflect on the following decades of research on non-shared environmental influence, the basic finding of the importance of non-shared environment has not been seriously challenged, which seems surprising to me given its far-reaching implications for understanding how the environment works. It should be emphasized that the message is not that all environmental variance for all traits is non-shared but rather that most environmental influence for most traits is non-shared. Some significant shared environmental variance has been found for some traits.5,6 For example, for antisocial behaviour in adolescence, shared environment accounts for ~15% of the total phenotypic variance, although even here non-shared environment accounts for much more of the variance, ~40%.7 Another example of significant shared environmental influence is academic achievement, where the effect is surprisingly modest in its magnitude given that this result is based on siblings growing up in the same family and being taught in the same school, often by the same teacher in the same classroom.8 Intelligence (IQ) is a third example, first mooted in the 1987 paper, showing significant shared environmental influence in childhood that diminishes to insignificant levels by adolescence to be subsumed by genetic and non-shared environmental influences, a suggestion subsequently confirmed in several studies and meta-analyses.9,10 A search for ‘nonshared environment OR non-shared environment’ using ISI Web of Science (February 2010) yields 371 entries, after excluding a few inappropriate entries. These 371 entries certainly underestimate the total number of papers in the area—e.g. the search does not even identify our 1987 paper or 29 of the 32 connected commentaries. In part this is due to the fact that non-shared environment has been called by other, less searchable names such as unique, specific and individual environment. Nonetheless, a ‘citation report’ of the 371 entries (Figure 1) is interesting for three reasons. First, it was not until the mid-1990s, a decade after the first papers, that non-shared environment began to be cited. Second, since then, citations of non-shared environment have steadily increased to more than a thousand per year by 2008. Open in a separate window Figure 1 Citations per year for 371 entries for ‘nonshared environment OR non-shared environment' from ISI Web of Science (March 2010)

Abstract: 1. Published data suggest that mean left-right asymmetry in number of sternopleural bristles of D. melanogaster declines when inbred lines are crossed, while the corresponding variance for sternite bristles remains unchanged. Some genetic tests were undertaken to analyse this difference in behaviour of the two characters.2. A progeny test on a wild stock showed that a small amount of genetic variance in sternopleural asymmetry was present, equivalent to about 2% of the total phenotypic variance.3. It was possible to increase and decrease the level of sternopleural asymmetry in two wild stocks by selection. These experiments gave an estimated heritability of some 2–3%, in close agreement with the progeny test. Change in asymmetry did not necessarily lead to a change in mean count.4. Homozygous lines, consisting of individual third chromosomes from the Renfrew wild stock made homozygous in an inbred line genetic background, were intercrossed, and the average indices for a number of characters of eight inter crosses involving eight lines were compared with their mid-parent averages. Thorax length was 2% greater and its variance 32% less in the crosses; total sternopleural count and its variance did not change significantly, but the asymmetry variance declined by 18%. In contrast, the corresponding asymmetry or independent variance for numbers of sternite bristles was 6% higher in the crosses, although the total sternite count and its variance did not change. These results fit in with previous work.5. Tests on a similar set of homozygous lines in which the third chromosomes came from the SP wild stock, and on some long inbred lines from the Pacific wild stock, gave discordant results. Of eight SP lines examined, four were homozygous for a gene polychaetoid, and four were homozygous for a genetic effect causing sockets without bristles to occur among the sternopleurals. Both types had much greater sternopleural variance and asymmetry than the Renfrew lines, and both indices declined sharply in intercrosses leaving these genetic effects heterozygous, but neither declined if they were left homozygous in the crosses. Similarly high sternopleural variances were found in the Pacific lines, but only the total variance declined in males and only the asymmetry variance declined in the females, when they were intercrossed. All the four Pacific lines tested appeared to be homozygous for a genetic effect which caused a variable number of dorso-central and scutellar bristles to be replaced by sockets without bristles, and an occasional extra scutellar bristle to appear. This effect was also probably responsible for the high sternopleural variances.6. Males of the Pacific inbred lines and intercrosses were compared when reared on the normal live medium and on a synthetic diet in reduced concentration, which reduced body-size by 23% (thorax area). The inbred lines were reduced more than the F1's in total sternopleural count and its variance, but the F1's were reduced more in sternopleural asymmetry, by the restricted diet.7. The problems of interpreting these experiments, in view of our ignorance of the biological functions and attributes of the sternopleural and sternite bristles, are discussed. It is concluded that we have no basis yet for deciding whether sternopleural bristle number is of adaptive significance, but this is considered improbable.8. The experimental evidence suggests that sternopleural asymmetry cannot be considered a measure of general developmental stability, particularly as the level of asymmetry can be reduced by selection well below that of typical wild stocks.9. The scaling problems arising when the mean asymmetry of lines with different mean counts are to be compared, are examined, and it is suggested that the ratio of asymmetry to total count does not eliminate scale effects.10. Developmental and anatomical differences between the sternopleural and sternite bristles suggest a possible reason why they behave differently when inbred lines are intercrossed.