A new study has for the first time identified regions of the genome
associated with left-handedness in the general population and linked their
effects with brain architecture. The study, led by researchers at the
University of Oxford who were funded by the Medical Research Council — part of
UK Research and Innovation — and Wellcome, linked these genetic differences with
the connections between areas of the brain related to language.
It was already known that genes have a partial role in determining
handedness — studies of twins have estimated that 25% of the variation in
handedness can be attributed to genes — but which genes these are had not been
established in the general population.
The new study, published in the journal Brain, identified some
of the genetic variants associated with left-handedness by analysing the
genomes of about 400,000 people from UK Biobank, which included 38,332
left-handers.
Of the four genetic regions they identified, three of these were associated
with proteins involved in brain development and structure. In particular, these
proteins were related to microtubules, which are part of the scaffolding inside
cells, called the cytoskeleton, which guides the construction and functioning
of the cells in the body.
Using detailed brain imaging from approximately 10,000 of these
participants, the researchers found that these genetic effects were associated
with differences in brain structure in white matter tracts, which contain the
cytoskeleton of the brain that joins language-related regions.
Dr Akira Wiberg, a Medical Research Council fellow at the University of
Oxford, who carried out the analyses, said: “Around 90% of people are
right-handed, and this has been the case for at least 10,000 years. Many
researchers have studied the biological basis of handedness, but using large
datasets from UK Biobank has allowed us to shed considerably more light on the
processes leading to left-handedness.”
“We discovered that, in left-handed participants, the language areas of the
left and right sides of the brain communicate with each other in a more
coordinated way. This raises the intriguing possibility for future research
that left-handers might have an advantage when it comes to performing verbal
tasks, but it must be remembered that these differences were only seen as
averages over very large numbers of people and not all left-handers will be
similar.”
Professor Gwenaëlle Douaud, joint senior author on the study, from the
Wellcome Centre for Integrative Neuroimaging at the University of Oxford, said:
“Many animals show left-right asymmetry in their development, such as snail
shells coiling to the left or right, and this is driven by genes for cell
scaffolding, what we call the “cytoskeleton.”
“For the first time in humans, we have been able to establish that these
handedness-associated cytoskeletal differences are actually visible in the
brain. We know from other animals, such as snails and frogs, that these effects
are caused by very early genetically-guided events, so this raises the
tantalising possibility that the hallmarks of the future development of
handedness start appearing in the brain in the womb.”
The researchers also found correlations between the genetic regions
involved in left-handedness and a very slightly lower chance of having
Parkinson’s disease, but a very slightly higher chance of having schizophrenia.
However, the researchers stressed that these links only correspond to a very
small difference in the actual number of people with these diseases, and are
correlational so they do not show cause-and-effect. Studying the genetic links
could help to improve understanding of how these serious medical conditions
develop.
Professor Dominic Furniss, joint senior author on the study, from the
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Science
at the University of Oxford, said: “Throughout history, left-handedness has
been considered unlucky, or even malicious. Indeed, this is reflected in the
words for left and right in many languages. For example, in English “right”
also means correct or proper; in French “gauche” means both left and clumsy.
“Here we have demonstrated that left-handedness is a consequence of the
developmental biology of the brain, in part driven by the complex interplay of
many genes. It is part of the rich tapestry of what makes us human.”
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