Genetic association for left-handedness

About 90 percent of the human population is right-handed — this has been the case for the last 10,000 years. But what sets lefties apart? A new study published in the journal Brain has identified the specific genes that are related to which hand you prefer.

We’ve known for a while that genes play a role in determining handedness. Studies of twins have shown that 25 percent of the variation can be explained by genetic makeup. But this is the first study to identify genome-wide significant loci (fixed positions on a chromosome, or where a gene “lives”) for human handedness in the general population.

Data were collected from the UK Biobank, a repository of biological information from a large group of people. A big part of what allowed them to identify these loci was the size of the study: it included approximately 400,000 people, 38,332 of whom were lefties. Dr. Akira Wiberg, a Medical Research Council fellow at the University of Oxford and the first author on the study, said in an Oxford University press release, “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."

The researchers identified four loci that were associated with handedness. Three of the four were also associated with encoding proteins involved in brain development and patterning.

“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,’” said Professor Gwenaëlle Douaud in thepress release, associate professor at the University of Oxford and joint senior author on the study. “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 tantalizing possibility that the hallmarks of the future development of handedness start appearing in the brain in the womb.”

The loci associated with left-handedness are also strongly positively correlated with schizophrenia, while they are negatively correlated with Parkinson’s disease. Of course, correlation does not imply causation. Deepening knowledge of these genes could, however, help scientists understand these diseases.

“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,” said Professor Dominic Furniss, associate professor at the University of Oxford, and also joint senior author on the study, in a press release.

But being left-handed could have some benefits. One striking result is that there is an increase in functional connectivity between right and left language networks in lefties. Detailed brain imaging of approximately 9,000 participants showed differences in white matter tracts, which contain the cytoskeleton of the brain that joins the language-related regions.

“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,” Dr. Wiberg said, but he warns that these results do not apply neatly to every individual. “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.”

The study does not definitively conclude whether increased coordination of language function gives left-handers a cognitive advantage at verbal tasks, the authors leaving this question to future investigations.