Skip to navigation Skip to main content Skip to footer

Approved research

Genetics of brain asymmetry and language-related disorders

Principal Investigator: Dr Clyde Francks
Approved Research ID: 16066
Approval date: March 1st 2016

Lay summary

Left-right asymmetry is an important feature of the human brain. One prominently asymmetric brain network underlies the uniquely human ability to speak and understand language. A lack of brain asymmetry is associated with variation in human cognitive abilities linked to language, and also susceptibility to cognitive disorders including language impairment and dyslexia. The genetic basis of human brain asymmetry is unknown, while links between asymmetric anatomy and function are poorly understood. It is likely that genes involved in brain asymmetry contain variants in the population that influence cognitive performance and cognitive disorders. We will test whether certain genetic profiles affect asymmetric brain structure and function particularly for regions involved in speaking and listening. We will also test whether these same genetic variations affect susceptibility to language-related disorders including dyslexia and Specific Language Impairment. Both can be severe disorders with lifelong impacts on achievement and mental health. Dyslexia is identified as a disability in the UK's Equality Act 2010. According to the British Dyslexia Association, roughly 4% of the population has severely impaired reading ability. Each illiterate pupil, by age 37, is estimated to cost taxpayers an extra roughly 50,000GBP. Some brain regions are asymmetrical and important for speech and language. We will use Biobank brain imaging data in combination with genetic data to identify genomic profiles linked to the thickness, surface area and volumes of these regions. If possible, we will also do a similar analysis with Biobank MRI data that measures how active the language regions are during rest. We will follow up the findings in other cohorts of people with brain imaging and genetic data, and language-related disorders and genetic data. We are leading members of scientific consortia that study these questions with meta-analysis. Data will be used from all Biobank participants who have done MRI scans (roughly 5000 at the time of writing, September 2015). We will also need the genotype data of as many of these participants as possible. The larger the available dataset, the more statistical power there is to detect and measure the individual and pooled effects of genomic variants on brain anatomy and function.

Left-right asymmetry is an important feature of the human brain. One prominently asymmetric brain network underlies the uniquely human ability to speak and understand language. A lack of brain asymmetry is associated with variation in human cognitive abilities linked to language, and also susceptibility to cognitive disorders including language impairment and dyslexia. The genetic basis of human brain asymmetry is unknown, while links between asymmetric anatomy and function are poorly understood. It is likely that genes involved in brain asymmetry contain variants in the population that influence cognitive performance and cognitive disorders.

Addendum to project application 16066. Effects of perinatal factors on hand preference

As outlined in the project application (16066), we are interested in left-right asymmetry of the human brain. A functional reflection of brain asymmetry is hand preference. In twin studies, hand preference was shown to have a heritability of ~ 25% (1, 2), while SNP-heritability in the UK-biobank data was 3% (3). It seems clear both genetic and environmental factors influence hand preference. Like other aspects of brain asymmetry, atypical handedness has been found to be associated with neurocognitive disorders, such as autism (4) or schizophrenia (5). In addition to genetic factors underlying brain asymmetry, which we also study in other parts of application 16066, we are interested in environmental correlates. Hand preference (field 1707) has received a lot of attention in both scientific and popular literature. Preference gets established before (6) or shortly after (7) birth. Previous studies have found various perinatal factors to be associated with the probability of being right- or left-handed, such as birth weight, being a twin, maternal smoking or having been breastfed (1, 8-13) and others. One difficulty is that many of these factors are interrelated to some extent, but not all have necessarily been measured in any given study, or else the range of variation available across these various factors has been too limited or biased by sample selection in order to disentangle them. The large, and thoroughly characterised, population-based cohort of the UK Biobank allows multiple potential factors to be considered together, while providing statistical power to begin to disentangle them. We propose to study hand preference in relation to the available 'Early life factors' breastfed as a baby (f.1677), adopted as a child (f.1767), part of a multiple birth (f.1777), maternal smoking around birth (f.1787) and birth weight (f.20022), as well as month of birth (f.52) to better understand this behavioural aspect of brain asymmetry. As some of these factors are heritable themselves (3, 14), we will also test whether genetic co-variation with hand preference can be detected.

References

  1. Medland SE, Duffy DL, Wright MJ, Geffen GM, Hay DA, Levy F, et al. Genetic influences on handedness: data from 25,732 Australian and Dutch twin families. Neuropsychologia. 2009;47(2):330-7.
  2. Suzuki K, Ando J. Genetic and environmental structure of individual differences in hand, foot, and ear preferences: A twin study. Laterality: Asymmetries of Body, Brain and Cognition. 2014;19(1):113-28.
  3. Ge T, Chen CY, Neale BM, Sabuncu MR, Smoller JW. Phenome-wide heritability analysis of the UK Biobank. PLoS Genet. 2017;13(4):e1006711.
  4. Markou P, Ahtam B, Papadatou-Pastou M. Elevated Levels of Atypical Handedness in Autism: Meta-Analyses. Neuropsychol Rev. 2017;27(3):258-83.
  5. Deep-Soboslay A, Hyde TM, Callicott JP, Lener MS, Verchinski BA, Apud JA, et al. Handedness, heritability, neurocognition and brain asymmetry in schizophrenia. Brain : a journal of neurology. 2010;133(10):3113-22.
  6. Hepper PG. The developmental origins of laterality: Fetal handedness. Developmental Psychobiology. 2013;55(6):588-95.
  7. Michel GF, Campbell JM, Marcinowski EC, Nelson EL, Babik I. Infant Hand Preference and the Development of Cognitive Abilities. Frontiers in Psychology. 2016;7:410.
  8. Davis A, Annett M. Handedness as a function of twinning, age and sex. Cortex. 1994;30(1):105-11.
  9. Ellis SJ, Ellis PJ, Marshall E. Hand preference in a normal population. Cortex. 1988;24(1):157-63.
  10. Heikkila K, Vuoksimaa E, Saari-Kemppainen A, Kaprio J, Rose RJ, Haukka J, et al. Higher Prevalence of Left-Handedness in Twins? Not After Controlling Birth Time Confounders. Twin Res Hum Genet. 2015;18(5):526-32.
  11. Denny K. Breastfeeding predicts handedness. Laterality. 2012;17(3):361-8.
  12. Hay DA, Howie PM. Handedness and differences in birthweight of twins. Perceptual and motor skills. 1980;51(2):666.
  13. Searleman A, Porac C, Coren S. Relationship between birth order, birth stress, and lateral preferences: a critical review. Psychol Bull. 1989;105(3):397-408.
  14. Neale B. Heritability of >2,000 traits and disorders in the UK Biobank 2017 [Available from: http://www.nealelab.is/blog/2017/9/15/heritability-of-2000-traits-and-disorders-in-the-uk-biobank.

Scope extension Feb2020:

Like other aspects of brain asymmetry, non-right-handedness is more frequent in some neurocognitive disorders, such as autism or schizophrenia. We aim to better understand the genetic and non-genetic contributions to various aspects of brain asymmetry, language-related cognition and behaviour, and brain disorders. We will explore whether brain asymmetry is associated with psychosocial factors, lifestyle and environmental factors, family history of brain illness, longitudinal changes, as well as genetic factors and their overlap with brain disorders.

We will also perform similar analyses to investigate brain structure-function-behaviour -genetic links more broadly than with reference only to brain asymmetry, using both univariate and multivariate approaches, followed by testing for overlap with psychiatric and neurocognitive disorders.

The human brain has various distinctive features compared to our closest evolutionary relatives. One goal is to identify potential candidate genes and biological pathways that are related to uniquely modern human phenotypes. This may help identifying recently evolved, and therefore inherently less stable, developmental pathways, and contribute to better understand developmental disorders in living people.

Extension Oct 2023:

Language is an important aspect of social cognition and interaction. Using genetic analyses, we want to understand how and when social phenotypes become a risk or beneficial factor for later-life health, psychosocial, educational, cognitive/language-related and lifestyle outcomes and social (family, partner, friendship) relationships, whether such links have signatures in the brain and whether genetic associations are biased through gene-environment (GE) correlations or non-random mating. We will combine UKB data with genome-wide information on social behaviour and related clinical conditions (e.g. with summary statistics from the EAGLE or PGC consortia) to investigate single-variant associations and patterns of genetic overlap. We will apply univariate and multivariate approaches to study polygenic association and genomic and non-genomic (residual) factors/factor structures underlying social behaviour and related/later-life outcomes directly in UKB participants, but also through summary statistics.