The molecular genetics of hand preference revisited
TL;DR: A genome-wide association analysis of hand preference in the large, population-based UK Biobank cohort used gene-set enrichment analysis to investigate whether genes involved in visceral asymmetry are particularly relevant to hand preference, following one previous report.
Abstract: Hand preference is a prominent behavioural trait linked to human brain asymmetry. A handful of genetic variants have been reported to associate with hand preference or quantitative measures related to it. Most of these reports were on the basis of limited sample sizes, by current standards for genetic analysis of complex traits. Here we performed a genome-wide association analysis of hand preference in the large, population-based UK Biobank cohort (N = 331,037). We used gene-set enrichment analysis to investigate whether genes involved in visceral asymmetry are particularly relevant to hand preference, following one previous report. We found no evidence supporting any of the previously suggested variants or genes, nor that genes involved in visceral laterality have a role in hand preference. It remains possible that some of the previously reported genes or pathways are relevant to hand preference as assessed in other ways, or else are relevant within specific disorder populations. However, some or all of the earlier findings are likely to be false positives, and none of them appear relevant to hand preference as defined categorically in the general population. Our analysis did produce a small number of novel, significant associations, including one implicating the microtubule-associated gene MAP2 in handedness.
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TL;DR: It is argued that the same evolutionary mechanisms should apply across geographical regions to maintain the roughly 1:10 ratio, while cultural factors, such as pressure against left-hand use, moderate the magnitude of the prevalence of left-handedness.
Abstract: Across time and place, right hand preference has been the norm, but what is the precise prevalence of left- and right-handedness? Frequency of left-handedness has shaped and underpinned different fields of research, from cognitive neuroscience to human evolution, but reliable distributional estimates are still lacking. While hundreds of empirical studies have assessed handedness, a large-scale, comprehensive review of the prevalence of handedness and the factors that moderate it, is currently missing. Here, we report 5 meta-analyses on hand preference for different manual tasks and show that left-handedness prevalence lies between 9.3% (using the most stringent criterion of left-handedness) to 18.1% (using the most lenient criterion of nonright-handedness), with the best overall estimate being 10.6% (10.4% when excluding studies assessing elite athletes' handedness). Handedness variability depends on (a) study characteristics, namely year of publication and ways to measure and classify handedness, and (b) participant characteristics, namely sex and ancestry. Our analysis identifies the role of moderators that require taking into account in future studies on handedness and hemispheric asymmetries. We argue that the same evolutionary mechanisms should apply across geographical regions to maintain the roughly 1:10 ratio, while cultural factors, such as pressure against left-hand use, moderate the magnitude of the prevalence of left-handedness. Although handedness appears as a straightforward trait, there is no universal agreement on how to assess it. Therefore, we urge researchers to fully report study and participant characteristics as well as the detailed procedure by which handedness was assessed and make raw data publicly available. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
183 citations
Cites background from "The molecular genetics of hand pref..."
...More recently, GWAS in ~ 400,000 samples of the UK Biobank led to the identification of just a handful of significant associations (de Kovel & Francks, 2019; Wiberg et al., 2019)....
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TL;DR: Novel animal models and approaches could be established in the last decades, and they already produced a substantial increase of knowledge, and insights from these comparative studies are crucial to understand the functions and pathologies of the authors' asymmetric brain.
Abstract: Comparative studies on brain asymmetry date back to the 19th century but then largely disappeared due to the assumption that lateralization is uniquely human. Since the reemergence of this field in the 1970s, we learned that left-right differences of brain and behavior exist throughout the animal kingdom and pay off in terms of sensory, cognitive, and motor efficiency. Ontogenetically, lateralization starts in many species with asymmetrical expression patterns of genes within the Nodal cascade that set up the scene for later complex interactions of genetic, environmental, and epigenetic factors. These take effect during different time points of ontogeny and create asymmetries of neural networks in diverse species. As a result, depending on task demands, left- or right-hemispheric loops of feedforward or feedback projections are then activated and can temporarily dominate a neural process. In addition, asymmetries of commissural transfer can shape lateralized processes in each hemisphere. It is still unclear if interhemispheric interactions depend on an inhibition/excitation dichotomy or instead adjust the contralateral temporal neural structure to delay the other hemisphere or synchronize with it during joint action. As outlined in our review, novel animal models and approaches could be established in the last decades, and they already produced a substantial increase of knowledge. Since there is practically no realm of human perception, cognition, emotion, or action that is not affected by our lateralized neural organization, insights from these comparative studies are crucial to understand the functions and pathologies of our asymmetric brain.
180 citations
TL;DR: The existing literature about atypical language dominance is summarized, the evidence for intermediate phenotypes in brain functional segregation that could bridge behavioral and genetic data is explored and the existence of at least three differentphenotypes in human functional segregation is suggested.
82 citations
Cites background from "The molecular genetics of hand pref..."
...A recent genome-wide association analysis of categorical hand preference in over 330,000 individuals of the general population, however, found no evidence supporting any of the previously suggested genes to be involved in hand preference and suggested that some or all of these findings may have been false positives [30]....
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University of Queensland1, Virginia Commonwealth University2, Karabük University3, University of Oslo4, University of Cambridge5, Wellcome Trust Sanger Institute6, University of Lausanne7, Utrecht University8, VU University Amsterdam9, Public Health Research Institute10, Statens Serum Institut11, German Center for Neurodegenerative Diseases12, University of Edinburgh13, Harvard University14, King's College London15, Queen Mary University of London16, QIMR Berghofer Medical Research Institute17, University of Tartu18, Broad Institute19, Martin Luther University of Halle-Wittenberg20, Indiana University – Purdue University Indianapolis21, University of Copenhagen22, University of Helsinki23, Erasmus University Rotterdam24, University of Bristol25, Hannover Medical School26, Swiss Institute of Bioinformatics27, University of Turku28, Icahn School of Medicine at Mount Sinai29, deCODE genetics30, University of Oxford31, Genentech32, Stanford University33, Queensland University of Technology34, University of California, Los Angeles35, Columbia University36, McMaster University37, University of Zagreb38, University of Split39, University of Surrey40, Imperial College London41, Radboud University Nijmegen42, Max Planck Society43, GlaxoSmithKline44, Lundbeck45
TL;DR: It is suggested that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10−8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders. A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.
78 citations
TL;DR: A model in which early life stress as well as chronic stress not only increases the risk for psychiatric and neurodevelopmental disorders but also changes structural and functional hemispheric asymmetries leading to the aberrant lateralization patterns seen in these disorders is proposed.
68 citations
References
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TL;DR: An inventory of 20 items with a set of instructions and response- and computational-conventions is proposed and the results obtained from a young adult population numbering some 1100 individuals are reported.
33,268 citations
TL;DR: The UK Biobank is described, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
Abstract: Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
6,114 citations
TL;DR: It is shown that the average statistical power of studies in the neurosciences is very low, and the consequences include overestimates of effect size and low reproducibility of results.
Abstract: A study with low statistical power has a reduced chance of detecting a true effect, but it is less well appreciated that low power also reduces the likelihood that a statistically significant result reflects a true effect. Here, we show that the average statistical power of studies in the neurosciences is very low. The consequences of this include overestimates of effect size and low reproducibility of results. There are also ethical dimensions to this problem, as unreliable research is inefficient and wasteful. Improving reproducibility in neuroscience is a key priority and requires attention to well-established but often ignored methodological principles.
5,683 citations
TL;DR: Deep phenotype and genome-wide genetic data from 500,000 individuals from the UK Biobank is described, describing population structure and relatedness in the cohort, and imputation to increase the number of testable variants to 96 million.
Abstract: The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
4,489 citations
01 Jan 1971
TL;DR: In this paper, an inventory of 20 items with a set of instructions and response-and computational-conventions is proposed and the results obtained from a young adult population numbering some 1100 individuals are reported.
Abstract: The need for a simply applied quantitative assessment of handedness is discussed and some previous forms reviewed. An inventory of 20 items with a set of instructions and response- and computational-conventions is proposed and the results obtained from a young adult population numbering some 1100 individuals are reported. The separate items are examined from the point of view of sex, cultural and socio-economic factors which might appertain to them and also of their inter-relationship to each other and to the measure com- puted from them all. Criteria derived from these considerations are then applied to eliminate 10 of the original 20 items and the results recomputed to provide frequency-distribution and cumulative frequency functions and a revised item-analysis. The difference of incidence of handedness between the sexes is discussed.
3,559 citations