What influences handedness?

Q: Why are only some people left-handed? Are there any genes behind this?

Krishna: Researchers examined rare genetic variants from a database of more than 350,000 individuals’ genetic data to hunt for clues for what influences handedness in humans. Their findings implicate tubulins — proteins that build cells’ internal skeletons.

The results, published on 2 April in Nature Communications (1), were obtained specifically at protein-coding parts of the DNA, and add to previous studies that linked genetic variations with handedness .

During the embryonic stage of human development, the left and right brain hemispheres get wired differently, which in part determines innate behaviours, such as where we lean when we hug someone, on which side of our mouth we tend to chew our food and, most prominently, which hand is our dominant one. This turns out to be the left hand for around 10% of the human population.

Studies looking at genome-wide data from UK Biobank(2) found 48 common genetic variants associated with left-handedness, which were mostly in non-coding regions of the DNA. These included sections that could control the expression of genes related to tubulins. These proteins assemble into long, tube-like filaments called microtubules, which control the shapes and movements of cells.

Researchers looked for genetic variants in protein-coding sequences. Their analysis of 313,271 right-handed and 38,043 left-handed individuals’ genetic data, from the UK Biobank, uncovered variants in a tubulin gene, dubbed TUBB4B, which were 2.7 times more common in left-handed people than in right-handers.

Microtubules could influence handedness because they form cilia — hair-like protrusions in cell membranes — which can direct fluid flows in an asymmetric way during development.

Left-handedness, affecting roughly 10-12% of people, is caused by a complex mix of genetics, developmental, and environmental factors. While not controlled by one single gene, it is linked to over 40 genetic markers, including rare variants of the TUBB4B gene, which influence brain asymmetry, neurodevelopment, and cell shape. 

Some interesting aspects of Left-Handedness: (3)

• Genetic Factors: While it runs in families, left-handedness does not follow simple inheritance patterns. If both parents are left-handed, the child has a higher chance of being left-handed (up to 27%), but most children of left-handed parents are still right-handed.
• Brain Asymmetry: For most people, the left hemisphere of the brain governs language and motor skills, leading to right-handedness. In left-handed individuals, the right hemisphere often plays a larger role in these functions.
• Biological & Environmental Drivers: Factors in the womb, such as testosterone levels, developmental conditions, and early life experiences, also play a significant role. It is considered a mix of genetics and environment (epigenetic factors).
• Developmental Start: Hand dominance often begins in the womb, with babies showing preferences by moving specific arms as early as 9-10 weeks.
• Rare Gene Variants: Recent studies suggest rare variants of genes controlling cell shape (like TUBB4B) are more common in left-handed people. 

In summary, left-handedness is not a single-gene trait but a biological variation stemming from complex polygenic factors (multiple genes with small effects). 

Footnotes:

1. Schijven, D., Soheili-Nezhad, S., Fisher, S. E. & Francks, C. Nature Commun. 15, 2632 (2024).

2. Cuellar-Partida, G. et al. Nature Hum. Behav. 5, 59–70 (2021).

3. https://en.wikipedia.org/wiki/Handedness#:~:text=Most%20research%20....