Gene loci responsible for hand dominance: relation to brain activity and mental disorders

by Alyssa Ausa (Polyplex)

What is "Handedness"? 

Approximately 90% of the human population identify their right hand as their dominant hand. Numerous activities such as writing, eating, and using tools or instruments require people to use their dominant hand in order to carry out the activity effectively. But how do we identify which hand is dominant? Does genetics have anything to do with the population bias in handedness?

Handedness is typically described as the hand which one prefers to use for unimanual tasks (Scharoun and Bryden, 2014). Hand preference for physical action develops early, specifically, before birth. Throughout infancy, childhood, and adolescence, an individual’s handedness becomes evident and is inclined to be constant all throughout his/her life. Handedness, particularly left-handedness, is thought to be caused by many different factors, and has been found to be linked to other conditions in humans, like mental disorders.

Genetics in Handedness, Language and Mental Diseases

Most people believe that the reason for the majority of people being right-handed is due to the localization of language in the left hemisphere of the brain, since the left hemisphere of the brain controls the movement on the right side of the body. Handedness tends to be apparent at the same time when language is developed. According to Goldman (2014), the specialization of the left hemisphere of the brain for language is common, and suggests that as the left hemisphere evolved, the preference for the right hand may have intensified as a side effect.

Neuroanatomical studies of human handedness have been equivocal, most likely owing to small- to medium-sized study populations (Hatta, 2007; Guadalupe et al., 2014). This means that very little is known about the connection of mental disorders to handedness and language. According to Brandler and Parachchini (2014), however, there are well-established associations between left-handedness and several neurodevelopmental disorders. A meta-analysis of different studies concluded that left-handedness was significantly more common in participants with schizophrenia.

In the past, there have been three reasonable genetic models of handedness, two of which are single-gene models, where it was proposed that one allele codes for right-handedness (and left hemisphere language dominance), while a second allele leaves the determination of lateralization to fluctuating asymmetry. On the other hand, one of the models was polygenic in nature, in which it stated that both left-handedness and strong right-handedness are deviations from the norm, which is moderate right-handedness. Although, this model has no specific details on the genetic aspect of handedness itself, other than left-handedness and strong right-handedness being largely descended from left-handed parentals (Bryden, 1997).

In this study, however, researchers have discovered three genome-wide significant loci, or positions, by comparing left- handers and right-handers. Comparing non-right-handers and right-handers uncovered one further locus. These loci – rs199512, rs45608532, rs13017199, and rs3094128 have been found to be significantly involved in brain development and patterning genes.

According to Wiberg et al. (2019), genes that are strongly involved in brain development and patterning are the MAP2, TUBB/MICB, and WNT3/MAPT genes. There is a common genetic influence on handedness, Parkinson’s disease, and many mental health phenotypes like neuroticism through single nucleotide polymorphisms (SNP) in the locus that is most associated with handedness, which is rs199512. SNPs are a type of genetic variation among people that represent a difference in a single DNA building block. Also, it has been noted that there is a strong indirect relationship between the allele predisposing to left-handedness at rs199512, which is at the MAPT gene, and Parkinson’s disease. The associated loci show a direct relationship between left-handedness and schizophrenia, and an indirect relationship between left-handedness and Parkinson’s disease. In particular, rs199512 was directly associated with structural connectivity measures in white matter tracts connecting language-related brain areas. White matter is composed of millions of bundles of axons (nerve fibers) that connect neurons in different brain regions into functional circuits (Fields, 2010). This locus, rs199512, has biological credibility in contributing to differences in neurodevelopmental connectivity of language areas. Therefore, the lateralization of brain language function is strongly related to handedness.

Handedness, similar with other traits, is not influenced by one factor only. Other studies suggest that other factors may also contribute to handedness such as environmental and cultural factors. But knowing that genetics has a role in it, helps us better understand that there is a possibility of having certain mental diseases related with handedness. It also suggests that treatment of some mental diseases for left-handers and right-handers are different and knowing its genetic basis helps in identifying better treatments needed. Although, the researchers point out being left-handed does not necessarily lead to being diagnosed with these mental disorders.

References:

Brandler W. M., & Paracchini S. (2014). The genetic relationship between handedness and neurodevelopmental disorders. Trends Mol Med; 20:84–9.

Bryden, M. P., Roy, E. A., Manus, I. C., & Mc Bulman-Fleming, M. B. (1997). On the genetics and measurement of human handedness. Laterality: Asymmetries of Body, Brain and Cognition, 2(3-4), pp. 317-336.

Fields R. D. (2010). Neuroscience. Change in the brain's white matter. Science (New York, N.Y.), 330(6005), 768–769. doi:10.1126/science.1199139

Goldman, J. G. (2014, December 16). Future - Evolution: Why are most of us right-handed?

Guadalupe T, Willems RM, Zwiers MP, Vasquez AA, Hoogman M, Hagoort P, et al. (2014). Differences in cerebral cortical anatomy of left-and right-handers. Front Psychology ; 5: p. 261.

Hatta T. (2007). Handedness and the brain: a review of brain-imaging techniques. Magn Reson Med; 6: pp. 99–112.

Scharoun, S. M., & Bryden, P. J. (2014). Hand preference, performance abilities, and hand selection in children. Frontiers in Psychology, 5. doi: 10.3389/fpsyg.2014.00082

Wiberg, A., Ng, M., Omran, Y. A., Alfaro-Almagro, F., Mccarthy, P., Marchini, J., … Furniss, D. (2019). Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics. Brain, 142(10), 2938–2947. doi: 10.1093/brain/awz257